[go: up one dir, main page]

CN111187130A - Process for producing para-substituted aryl compound - Google Patents

Process for producing para-substituted aryl compound Download PDF

Info

Publication number
CN111187130A
CN111187130A CN202010063307.1A CN202010063307A CN111187130A CN 111187130 A CN111187130 A CN 111187130A CN 202010063307 A CN202010063307 A CN 202010063307A CN 111187130 A CN111187130 A CN 111187130A
Authority
CN
China
Prior art keywords
substituted
heteroatoms
halogen
group
aryl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202010063307.1A
Other languages
Chinese (zh)
Other versions
CN111187130B (en
Inventor
王鹏
陈小月
聂晓雪
吴奕晨
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Institute of Organic Chemistry of CAS
Original Assignee
Shanghai Institute of Organic Chemistry of CAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanghai Institute of Organic Chemistry of CAS filed Critical Shanghai Institute of Organic Chemistry of CAS
Priority to CN202010063307.1A priority Critical patent/CN111187130B/en
Publication of CN111187130A publication Critical patent/CN111187130A/en
Application granted granted Critical
Publication of CN111187130B publication Critical patent/CN111187130B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
    • C07C1/321—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C07C227/10—Formation of amino groups in compounds containing carboxyl groups with simultaneously increasing the number of carbon atoms in the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/353—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by isomerisation; by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
    • C07D211/96—Sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/26—Oxygen atoms attached in position 2 with hetero atoms or acyl radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
    • C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
    • C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
    • C07D303/23—Oxiranylmethyl ethers of compounds having one hydroxy group bound to a six-membered aromatic ring, the oxiranylmethyl radical not being further substituted, i.e.
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/36—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/18—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member containing only hydrogen and carbon atoms in addition to the ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
    • C07D327/06—Six-membered rings
    • C07D327/08—[b,e]-condensed with two six-membered carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/08—Hydrogen atoms or radicals containing only hydrogen and carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/08—Six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0805—Compounds with Si-C or Si-Si linkages comprising only Si, C or H atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
    • C07F7/083—Syntheses without formation of a Si-C bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明公开了一种如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，包括以下步骤：惰性气氛下，溶剂中，在碱和钯催化剂的作用下，如式(II)所示的芳基锍盐与如式(III)所示的硼化物进行偶联反应，即可。该方法以单取代芳烃为底物，原位构建芳基锍盐，钯催化剂催化原位构建的芳基锍盐发生Suzuki‑Miyaura偶联反应，快速高效构建单取代芳烃对位芳基化或烯基化产物。该方法条件温和，底物普适性高，杂环偶联底物耐受性广泛。

Figure DDA0002375181180000011
The invention discloses a preparation method of a para-substituted aryl compound represented by formula (I), which is characterized by comprising the following steps: in an inert atmosphere, in a solvent, under the action of a base and a palladium catalyst, as shown in the formula The arylsulfonium salt represented by (II) and the boride represented by the formula (III) may be subjected to a coupling reaction. The method uses mono-substituted aromatic hydrocarbons as substrates to construct aryl sulfonium salts in situ, and palladium catalyst catalyzes the Suzuki-Miyaura coupling reaction of the in situ constructed aryl sulfonium salts to rapidly and efficiently construct para-arylation or alkene of mono-substituted aromatic hydrocarbons. base product. The method has mild conditions, high substrate versatility, and wide tolerance to heterocyclic conjugated substrates.
Figure DDA0002375181180000011

Description

Process for producing para-substituted aryl compound
Technical Field
The invention relates to a preparation method of a para-substituted aryl compound.
Background
Para-substituted aryl compounds are widely found in natural products, active drug molecules, and pesticides. For example: losartan is an antihypertensive drug; canagliflozin which is useful in the treatment of diabetes; celecoxib can be used for treating arthritis. These active molecules all contain a diaryl structure. Thus, it is of great interest to develop simple and efficient methods for constructing diaryl compounds.
The traditional arylation cross-coupling reaction needs to introduce active halogen or organic metal compound into a reaction site in advance, and compared with the prior art, the method for realizing the arylation reaction directly from a C-H bond is the most attractive and promising method. One of the great obstacles to the direct arylation of simple aromatics is the precise control of site selectivity without a directing group during the functionalization of the C-H bond, especially when there are multiple reactive sites with subtle spatial and electrical differences. The para-arylation reaction of mono-substituted aromatics remains a significant challenge.
Yu group of subjects (Yu, j.q.et al.j.am. chem.soc.2011,133,13864) and Cheng group of subjects (Cheng, c. — h.et al.angelw.chem., int.ed.2011,50,9880) reported in 2011 respectively a Pd-catalyzed para-arylation reaction of mono-substituted aromatic hydrocarbons (alkylbenzenes, halobenzenes, and alkoxybenzenes), which are highly likely to undergo Pd (iv) intermediates. Subsequently, the Ye topic group (Ye, m.et al.j.am.chem.soc.2017,139,1786) reported in 2017 ligand-controlled Pd-catalyzed cross-coupling of mono-substituted arenes with aryl boronic acids.
For both types of reactions, the mono-substituted aromatic hydrocarbon is in large excess, which also indicates that the mono-substituted aromatic hydrocarbon has low reactivity and is not suitable for late functionalization of complex substrates; meanwhile, the substrate type is single, and the method is only suitable for common alkyl benzene and halogenated aromatic hydrocarbon. On the other hand, the existing methods have poor tolerance to heterocyclic coupling substrates. Therefore, a method beneficial to para-selective substitution of mono-substituted aromatic hydrocarbon is urgently needed to be found, and the conditions of mild conditions, high substrate universality and wide tolerance of heterocyclic coupling substrates are met.
Disclosure of Invention
Aiming at the defects of single substrate type and poor tolerance to heterocyclic coupling substrates in the method for preparing the para-substituted aryl compound by para-selective substitution of mono-substituted aromatic hydrocarbon in the prior art, the method for preparing the para-substituted aryl compound takes the mono-substituted aromatic hydrocarbon as the substrate, aryl sulfonium salt is built in situ, palladium catalyst catalyzes the aryl sulfonium salt built in situ to generate Suzuki-Miyaura coupling reaction, and the para-arylation or alkenylation product of the mono-substituted aromatic hydrocarbon is quickly and efficiently built. The method has the advantages of mild conditions, high substrate universality and wide tolerance of the heterocyclic coupling substrate.
The invention provides a preparation method of a para-substituted aryl compound shown as a formula (I), which comprises the following steps:
under the action of alkali and a palladium catalyst in a solvent in an inert atmosphere, performing coupling reaction on aryl sulfonium salt shown as a formula (II) and boride shown as a formula (III);
Figure BDA0002375181170000021
wherein,
x is O or S;
y is OTf, TFA or BF4；
R is amino, hydroxyl, halogen, 3-7 membered heterocycloalkyl containing 1 or 2 heteroatoms selected from O, S and N, 4-6 membered cycloalkyl, -COOR4、-OR5C1-C10 alkyl, RASubstituted C1-C10 alkyl, C1-C10 alkoxy, RBSubstituted C1-C10 alkoxy, C6-C10 aryl, RCSubstituted C6-C10 aryl, benzyl, RDA substituted benzyl group,
Figure BDA0002375181170000022
Figure BDA0002375181170000023
R4Is H or C1-C3 alkyl;
R5is C6-C10 aryl, R5ASubstituted C6-C10 aryl or acetyl; r5AIs halogen, amino, nitro, C1-C3 alkyl, C1-C3 alkoxy, -NHMs or
Figure BDA0002375181170000024
RAIs halogen, acetoxy (OAc), C1-C3 alkoxy, -NPhth, -COOR6Or "3-7 membered heterocycloalkyl containing 1 or 2 heteroatoms, which is one or more of O, S and N"; r6Is H or C1-C3 alkyl;
RBis halogen, carboxyl, C6-C10 aryl or "3-7 membered heterocycloalkyl containing 1 or 2 heteroatoms, which is one or more of O, S and N";
RCand RDIndependently halogen, carboxy-substituted C1-C3 alkyl, C1-C3 alkyl, or C1-C3 alkoxy;
R1and R2Independently H OR C1-C10 alkyl, OR1And OR2Together with the boron atom to which they are both attached form a 5-6 membered heterocycloalkyl or a C1-C3 alkyl substituted 5-6 membered heterocycloalkyl;
R3is C6-C10 aryl, RFSubstituted C6-C10 aryl, 5-12 membered heteroaryl containing 1-4 heteroatoms, wherein the heteroatoms are one or more of O, S and N, and RGSubstituted 5-12 membered heteroaryl having 1-4 heteroatoms of one or more of O, S and N or
Figure BDA0002375181170000031
RFAnd RGIndependently halogen, amino, nitro, hydroxy, TMS, acetyl, -SR10、-COOR11C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C1-C6 alkoxy, halogen-substituted C1-C6 alkoxy or C6-C10 aryl; r10Is C1-C3 alkyl; r11Is H or C1-C3 alkyl;
R7、R8and R9Is defined as any one of the following (i) to (iii):
(i)R7、R8and R9Independently H, C1-C10 alkyl, halogen substituted C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, RESubstituted C6-C10 aryl, 5-12 membered heteroaryl containing 1-4 heteroatoms, which are one or more of O, S and N, or-COOR12，R12Is C1-C3 alkyl; rEIs halogen, acetoxy (OAc), C1-C3 alkyl, halogen substituted C1-C3 alkyl, C1-C3 alkoxy, halogen substituted C1-C3 alkoxy, -NPhth or-COOR13，R13Is C1-C3 alkyl;
(ii)R7is H, R8And R9Together with the carbon atoms to which they are commonly attached form a 4-6 membered cycloalkyl group;
(iii)R7、R8and a carbon-carbon double bond connected with the N-carbon double bond to form '5-7-membered heterocyclic alkenyl containing 1-2 heteroatoms, wherein the heteroatoms are one or more of O, S and N', and R7ASubstituted' containing 1 ℃2 heteroatoms selected from O, S and one or more of N, 5-7 membered heterocycloalkenyl, 5-7 membered cycloalkylenyl or
Figure BDA0002375181170000032
R9Is H; r7AIs C1-C3 alkyl or tert-butyloxycarbonyl (Boc).
In a certain embodiment, X is S.
Preferably, in R, the halogen is F, Cl, Br or I, such as F or Cl.
Preferably, in R, the "3-7 membered heterocycloalkyl group containing 1 or 2 heteroatoms of one or more of O, S and N" is "a 3-6 membered heterocycloalkyl group containing 1 or 2 heteroatoms of O and/or N", such as an oxirane group (e.g., ethylene oxide group)
Figure BDA0002375181170000033
) Tetrahydrofuranyl, tetrahydropyranyl (e.g. of the formula
Figure BDA0002375181170000034
) Or morpholinyl (e.g.
Figure BDA0002375181170000035
)。
Preferably, in R, the 4-6 membered cycloalkyl is a 5-6 membered cycloalkyl, such as cyclopentyl or cyclohexyl.
Preferably, R4Wherein said C1-C3 alkyl is methyl, ethyl, n-propyl or isopropyl;
preferably, R5The C6-C10 aryl group and the R5AThe C6-C10 aryl group of the substituted C6-C10 aryl groups is independently phenyl or naphthyl.
Preferably, R5AWherein the halogen is F, Cl, Br or I.
Preferably, R5AWherein the C1-C3 alkyl is methyl, ethyl, n-propyl or isopropyl.
Preferably, R5AWherein the C1-C3 alkoxy is methoxy, ethoxy, n-propoxy or isopropoxy.
Preferably, R is5AR in substituted C6-C10 aryl5AThe number of substitution(s) may be 1 to 3 (e.g., 1 or 2), each R5AThe same or different.
In a certain embodiment, R5AIs halogen, nitro, -NHMs or
Figure BDA0002375181170000041
Preferably, in R, the C1-C10 alkyl group and the RAThe C1-C10 alkyl group of the substituted C1-C10 alkyl groups is independently a C1-C6 alkyl group, such as a C1-C3 alkyl group, further such as methyl, ethyl, n-propyl or isopropyl.
Preferably, RAWherein the halogen is F, Cl, Br or I.
Preferably, RAWherein the C1-C3 alkoxy is methoxy, ethoxy, n-propoxy or isopropoxy.
Preferably, R6Wherein the C1-C3 alkyl is methyl, ethyl, n-propyl or isopropyl.
Preferably, RAThe "3-7 membered heterocycloalkyl group containing 1 or 2 hetero atoms and one or more of O, S and N" is "a 3-6 membered heterocycloalkyl group containing 1 or 2 hetero atoms and hetero atoms of O and/or N", for example, an oxirane group (e.g., an ethylene oxide group)
Figure BDA0002375181170000042
) Tetrahydrofuranyl, tetrahydropyranyl (e.g. of the formula
Figure BDA0002375181170000043
) Or morpholinyl (e.g.
Figure BDA0002375181170000044
)。
In a certain embodiment, RAIs halogen, acetoxy, C1-C3 alkoxy, -NPhth or-COOR6。
Preferably, in R, the C1-C10 alkoxy group and the RBThe C1-C10 alkoxy group of the substituted C1-C10 alkoxy groups is independently C1-C6 alkoxy, for example C1-C3 alkoxy, further for example methoxy, ethoxy, n-propoxy or isopropoxy.
Preferably, RBWherein the halogen is F, Cl, Br or I.
Preferably, RBWherein said C6-C10 aryl is phenyl or naphthyl, such as phenyl.
Preferably, RBThe "3-7 membered heterocycloalkyl group containing 1 or 2 hetero atoms and one or more of O, S and N" is "a 3-6 membered heterocycloalkyl group containing 1 or 2 hetero atoms and hetero atoms of O and/or N", for example, an oxirane group (e.g., an ethylene oxide group)
Figure BDA0002375181170000051
) Tetrahydrofuranyl, tetrahydropyranyl (e.g. of the formula
Figure BDA0002375181170000052
) Or morpholinyl (e.g.
Figure BDA0002375181170000053
)。
In a certain embodiment, RBIs halogen or "3-6 membered heterocycloalkyl containing 1 or 2 heteroatoms, which are O and/or N".
Preferably, in R, the C6-C10 aryl group and the RCThe C6-C10 aryl group of the substituted C6-C10 aryl groups is independently phenyl or naphthyl.
Preferably, in R, R isCR in substituted C6-C10 arylCThe number of substitution(s) may be 1 to 3 (e.g., 1 or 2), each RCThe same or different.
Preferably, in R, R isDR in substituted benzylDThe number of substitution(s) may be 1 to 3 (e.g., 1 or 2), each RDThe same or different.
Preferably, RCOr RDWherein the halogen is F, Cl, Br or I.
Preferably, RCOr RDWherein the C1-C3 alkyl group of the C1-C3 alkyl group and the C1-C3 alkyl group which are substituted by carboxyl are independentOr methyl, ethyl, n-propyl or isopropyl.
Preferably, RCOr RDIn the carboxyl-substituted C1-C3 alkyl group, the number of substitution of carboxyl groups may be 1 to 2 (for example, 1).
Preferably, RCOr RDWherein the C1-C3 alkoxy is methoxy, ethoxy, n-propoxy or isopropoxy.
In a certain embodiment, R is halogen, C1-C10 alkyl, RASubstituted C1-C10 alkyl, C1-C10 alkoxy, RBSubstituted C1-C10 alkoxy, 3-6 membered heterocycloalkyl having 1 or 2 heteroatoms, O and/or N, 5-6 membered cycloalkyl, -COOR4、-OR5C6-C10 aryl, RCSubstituted C6-C10 aryl, benzyl,
Figure BDA0002375181170000054
Figure BDA0002375181170000055
Preferably, R1Or R2The C1-C10 alkyl group is a C1-C6 alkyl group, such as a C1-C3 alkyl group, and further such as a methyl group, an ethyl group, an n-propyl group or an isopropyl group.
Preferably, when OR1And OR2When they form a 5-to 6-membered heterocycloalkyl group or a C1-C3 alkyl-substituted 5-to 6-membered heterocycloalkyl group together with a boron atom to which they are both bonded, the 5-to 6-membered heterocycloalkyl group in the 5-to 6-membered heterocycloalkyl group and the 5-to 6-membered heterocycloalkyl group is
Figure BDA0002375181170000061
Preferably, the number of C1-C3 alkyl groups substituted in the C1-C3 alkyl-substituted 5-to 6-membered heterocycloalkyl group may be 2 to 6 (e.g., 4).
Preferably, the C1-C3 alkyl group of the C1-C3 alkyl-substituted 5-to 6-membered heterocycloalkyl group is a methyl group, an ethyl group, an n-propyl group or an isopropyl group, such as a methyl group.
Preferably, the C1-C3 alkyl-substituted 5-to 6-membered heterocycloalkyl group is
Figure BDA0002375181170000062
In a certain embodiment, R1And R2Is H, OR OR1And OR2Together with the boron atom to which they are both attached form a C1-C3 alkyl-substituted 5-to 6-membered heterocycloalkyl group (e.g.
Figure BDA0002375181170000063
)。
Preferably, R3The C6-C10 aryl group and the RFThe C6-C10 aryl group of the substituted C6-C10 aryl group is phenyl or naphthyl.
Preferably, R3In (1), the RFR in substituted C6-C10 arylFThe number of substitution(s) may be 1 to 5 (e.g., 1, 2, 3, 4 or 5), each RFThe same or different.
Preferably, R3Wherein the "5-12 membered heteroaryl group containing 1 to 4 hetero atoms and one or more of O, S hetero atoms and N" and RGThe "5-12 membered heteroaryl group containing 1 to 4 hetero atoms and one or more hetero atoms of O, S and N" in the substituted "5-12 membered heteroaryl group containing 1 to 4 hetero atoms and one or more hetero atoms of O, S and N" is independently "5-10 membered heteroaryl group containing 1 to 2 hetero atoms and one or more hetero atoms of O, S and N", for example, furyl group (e.g., furyl group)
Figure BDA0002375181170000064
) Pyridyl (e.g. pyridine)
Figure BDA0002375181170000065
) Thienyl (e.g.
Figure BDA0002375181170000066
) Benzothienyl (e.g. benzothienyl)
Figure BDA0002375181170000071
) Benzofuranyl radicals (e.g. benzofuranyl)
Figure BDA0002375181170000072
) Or quinolyl (e.g. quinolyl)
Figure BDA0002375181170000073
Figure BDA0002375181170000074
)。
Preferably, R3In (1), the RGR in substituted 5-12 membered heteroaryl containing 1-4 heteroatoms of one or more of O, S and NGThe number of substitution(s) may be 1 to 3 (e.g., 1 or 2), each RGThe same or different.
Preferably, RFOr RGWherein the halogen in the halogen, the halogen substituted C1-C6 alkyl group, and the halogen substituted C1-C6 alkoxy group is independently F, Cl, Br, or I.
Preferably, RFOr RGWherein the C1-C6 alkyl of the C1-C6 alkyl and the halogen substituted C1-C6 alkyl is independently C1-C3 alkyl, such as methyl, ethyl, n-propyl or isopropyl.
Preferably, RFOr RGThe number of halogen substitution in the halogen-substituted C1-C6 alkyl group may be 1 to 6 (e.g., 3).
Preferably, RFOr RGWherein said halogen substituted C1-C6 alkyl is-CF3。
Preferably, RFOr RGWherein the C1-C6 alkoxy of the C1-C6 alkoxy and the halogen substituted C1-C6 alkoxy is independently C1-C3 alkoxy, such as methoxy, ethoxy, n-propoxy, or isopropoxy.
Preferably, RFOr RGThe number of halogen substituted in the halogen-substituted C1-C6 alkoxy group may be 1 to 6 (e.g., 3).
Preferably, RFOr RGWherein said halogen-substituted C1-C6 alkoxy group is-OCF3。
Preferably, RFOr RGWherein, the C6-C10 aryl is phenyl or naphthyl.
In a certain embodiment, RFIs halogen, nitro, TMS, acetyl, -SR10、-COOR11C1-C6 alkyl, halogen substituted C1-C6 alkyl, C1-C6 alkoxy, halogen substituted C1-C6 alkoxy or C6-C10 aryl.
In a certain embodiment, RGIs halogen.
Preferably, R10Or R11Wherein the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl (e.g., methyl or ethyl).
Preferably, R7、R8Or R9Wherein the halogen in the halogen substituted C1-C6 alkyl is F, Cl, Br or I.
Preferably, R7、R8Or R9Wherein C1-C10 alkyl of said C1-C10 alkyl and said halogen substituted C1-C10 alkyl is independently C1-C6 alkyl, such as C1-C3 alkyl, further such as methyl, ethyl, n-propyl or isopropyl.
Preferably, R7、R8Or R9The number of halogen substitution in the halogen-substituted C1-C10 alkyl group may be 1 to 6 (e.g., 3).
Preferably, R7、R8Or R9Wherein said halogen substituted C1-C10 alkyl is-CF3。
Preferably, R7、R8Or R9The C1-C10 alkoxy group is a C1-C6 alkoxy group, such as a C1-C3 alkoxy group, further such as a methoxy group, an ethoxy group, an n-propoxy group or an isopropoxy group.
Preferably, R7、R8Or R9The C6-C10 aryl group and the REThe C6-C10 aryl group of the substituted C6-C10 aryl group is phenyl or naphthyl.
Preferably, R7、R8Or R9Wherein the "5-12 membered heteroaryl group containing 1 to 4 hetero atoms and one or more of O, S and N" is a "5-10 membered heteroaryl group containing 1 to 2 hetero atoms and one or more of O, S and N", such as furyl (e.g., furyl)
Figure BDA0002375181170000081
) Pyridyl (e.g. pyridine)
Figure BDA0002375181170000082
) Thienyl (e.g.
Figure BDA0002375181170000083
) And the like.
Preferably, REWherein the halogen in the halogen, the halogen substituted C1-C3 alkyl group, and the halogen substituted C1-C3 alkoxy group is independently F, Cl, Br, or I.
Preferably, REWherein the C1-C3 alkyl of the C1-C3 alkyl and the halogen substituted C1-C3 alkyl is independently methyl, ethyl, n-propyl or isopropyl.
Preferably, REThe number of halogen substitution in the halogen-substituted C1-C3 alkyl group may be 1 to 6 (e.g., 3).
Preferably, REWherein said halogen substituted C1-C3 alkyl is-CF3。
Preferably, REWherein the C1-C3 alkoxy of the C1-C3 alkoxy and the halogen substituted C1-C3 alkoxy is independently methoxy, ethoxy, n-propoxy or isopropoxy.
Preferably, REThe number of halogen substituted in the halogen-substituted C1-C3 alkoxy group may be 1 to 6 (e.g., 3).
Preferably, REWherein said halogen-substituted C1-C3 alkoxy group is-OCF3。
Preferably, R7、R8Or R9In (1), the RESubstituted C6-C10 aryl is halogen substituted C6-C10 aryl, for example halogen substituted phenyl.
Preferably, R12Or R13Wherein said C1-C3 alkyl is methyl, ethyl, n-propyl or isopropyl, such as methyl or ethyl.
In one embodiment, when R7、R8And R9Is defined as when in (i), R7、R8And R9Independently H, C1-C10 alkyl, C6-C10 aryl, RESubstituted C6-C10 aryl, 5-10 membered heteroaryl containing 1-2 heteroatoms, wherein the heteroatoms are one or more of O, S and N, or-COOR12And R is7、R8And R9Not H at the same time.
In one embodiment, when R7、R8And R9Is defined as when in (i), R7Is H, R8And R9Independently H, C1-C10 alkyl, C6-C10 aryl, halogen substituted C6-C10 aryl, 5-10 membered heteroaryl containing 1-2 heteroatoms and one or more of O, S and N, or-COOR12And R is8And R9Not H at the same time.
Preferably, when R is7、R8And R9(iii) when defined as in (ii), the 4-6 membered cycloalkyl group is a 5-6 membered cycloalkyl group, for example cyclopentane or cyclohexane.
Preferably, when R is7、R8And R9(iv) is defined as the "5-to 7-membered heterocycloalkenyl group containing 1 to 2 hetero atoms, the hetero atom being one or more of O, S and N" and the R when mentioned in (iii)7AThe "5-to 7-membered heterocycloalkenyl group containing 1 to 2 hetero atoms and one or more hetero atoms of O, S and N" in the substituted "5-to 7-membered heterocycloalkenyl group containing 1 to 2 hetero atoms and one or more hetero atoms of O, S and N" is "5-to 6-membered heterocycloalkenyl group containing 1 to 2 hetero atoms and hetero atoms of O and/or N", for example
Figure BDA0002375181170000091
Preferably, R is7AR in substituted 5-7 membered heterocycloalkenyl containing 1-2 heteroatoms selected from O, S and N7AThe number of substitution(s) may be 1 to 3 (e.g., 1 or 2), each R7AThe same or different.
Preferably, R is7AWherein the C1-C3 alkyl is methyl, ethyl, n-propyl orIsopropyl, such as methyl or ethyl.
Preferably, R is7AThe substituted 5-to 7-membered heterocycloalkenyl group containing 1 to 2 hetero atoms, which is one or more of O, S and N is
Figure BDA0002375181170000092
Preferably, when R is7、R8And R9When defined as in (iii), the 5-to 7-membered cycloalkenyl group is 5-to 6-membered cycloalkenyl, for example
Figure BDA0002375181170000093
In one embodiment, certain groups of the arylsulfonium salts of formula (II) are defined as follows, and undefined groups are as described in the previous embodiment:
x is S; r is halogen, C1-C10 alkyl, RASubstituted C1-C10 alkyl, C1-C10 alkoxy, RBSubstituted C1-C10 alkoxy, 3-6 membered heterocycloalkyl having 1 or 2 heteroatoms, O and/or N, 5-6 membered cycloalkyl, -COOR4、-OR5C6-C10 aryl, RCSubstituted C6-C10 aryl, benzyl,
Figure BDA0002375181170000101
Figure BDA0002375181170000102
In one embodiment, the boride of formula (III) is defined as follows, with undefined groups as described in the previous embodiment:
R1and R2Is H, R3Is C6-C10 aryl, RFSubstituted C6-C10 aryl, 5-12 membered heteroaryl containing 1-4 heteroatoms, wherein the heteroatoms are one or more of O, S and N, or RGSubstituted 5-12 membered heteroaryl containing 1-4 heteroatoms, which are one or more of O, S and N.
In one embodiment, the boride of formula (III) is defined as follows, with undefined groups as described in the previous embodiment:
OR1and OR2Together with the boron atom to which they are both attached form a C1-C3 alkyl-substituted 5-to 6-membered heterocycloalkyl group (e.g.
Figure BDA0002375181170000103
)；R3Is C6-C10 aryl, RFSubstituted C6-C10 aryl, 5-12 membered heteroaryl containing 1-4 heteroatoms, wherein the heteroatoms are one or more of O, S and N, or RGSubstituted 5-12 membered heteroaryl containing 1-4 heteroatoms, which are one or more of O, S and N.
In one embodiment, the boride of formula (III) is defined as follows, with undefined groups as described in the previous embodiment:
OR1and OR2Together with the boron atom to which they are both attached form a C1-C3 alkyl-substituted 5-to 6-membered heterocycloalkyl group (e.g.
Figure BDA0002375181170000104
)；R3Is composed of
Figure BDA0002375181170000105
Preferably, the aryl sulfonium salt shown in the formula (II) is selected from any one of the following structures:
Figure BDA0002375181170000111
Figure BDA0002375181170000121
preferably, the boride represented by the formula (III) is selected from any one of the following structures:
Figure BDA0002375181170000122
Figure BDA0002375181170000131
in the preparation method of the para-substituted aryl compound shown in the formula (I), the palladium catalyst can be a catalyst commonly used in the reaction in the field, and preferably, the palladium catalyst is Pd (I)tBu3P)2、Pd(PPh3)4、PdCl2(PPh3)2、PdCl2(dppf)、PdCl2(MeCN)2、Pd(OAc)2And Pd2(dba)3One or more of; more preferably, the palladium catalyst is Pd (C)tBu3P)2、Pd(PPh3)4、Pd(OAc)2And Pd2(dba)3(e.g. Pd: (a))tBu3P)2). Further, when the palladium catalyst is Pd (OAc)2Or Pd2(dba)3When the reaction system is used, a ligand can be added, and the ligand can be PPh3、BrettPhos、P(Cy)3、P(tBu)3And Brettphos, e.g. PPh3Brettphos and P (Cy)3One or more of (a).
In the preparation method of the para-substituted aryl compound shown in the formula (I), the palladium catalyst can be used in an amount which is conventional in such reactions in the art, and preferably, the molar ratio of the palladium catalyst to the aryl sulfonium salt shown in the formula (II) is 1: (10-40), for example 1:10, 1:20 or 1: 40.
In the preparation method of the para-substituted aryl compound shown in the formula (I), the inert atmosphere can be an inert atmosphere commonly used in the art, such as nitrogen or argon.
In the method for preparing the para-substituted aryl compound represented by formula (I), the solvent may be a solvent conventional in the art for such reactions, and preferably, the solvent is one or more of amide solvents, sulfoxide solvents, ketone solvents, alcohol solvents, nitrile solvents and haloalkane solvents, wherein the amide solvents may be one or more of N-methylpyrrolidone, dimethylformamide and dimethylacetamide (such as dimethylformamide or dimethylacetamide); the sulfoxide solvent can be dimethyl sulfoxide; the ketone solvent may be acetone; the alcohol solvent can be one or more of methanol, ethanol and 2-methyl-2-butanol; the nitrile solvent may be acetonitrile; the haloalkane solvent can be dichloromethane and/or dichloroethane (e.g., dichloromethane).
More preferably, the solvent is one or more of an amide solvent, a ketone solvent, an alcohol solvent and a halogenated alkane solvent, for example, the solvent is a mixed solvent of a halogenated alkane solvent and an "amide solvent, a ketone solvent or an alcohol solvent".
In the preparation method of the para-substituted aryl compound shown in the formula (I), the solvent can be used in an amount which is conventional in the art for such reactions, and preferably, the molar volume ratio of the aryl sulfonium salt shown in the formula (II) to the solvent is 0.01-5.0mol/L, for example, 0.1 mol/L.
In the preparation method of the para-substituted aryl compound shown in the formula (I), the base can be a base commonly used in the reaction in the field, and preferably, the base is alkali metal acetate (such as one or more of potassium acetate KOAc, sodium acetate NaOAc, cesium acetate CsOAc and lithium acetate LiOAc), alkali metal carbonate (such as potassium carbonate K)2CO3Sodium carbonate Na2CO3Lithium carbonate Li2CO3And cesium carbonate Cs2CO3One or more of), alkali metal bicarbonate (e.g., potassium bicarbonate, KHCO)3Sodium bicarbonate NaHCO3And cesium bicarbonate CsHCO3One or more of), an alkali metal carboxylate (e.g., one or more of potassium formate, sodium formate, potassium pivalate, sodium pivalate, and cesium pivalate), an alkali metal alkoxide (e.g., sodium methoxide CH)3ONa, potassium methoxide CH3OK, sodium ethoxide C2H5ONa and Potassium ethoxide C2H5OK), alkali metal fluoride (e.g., one or more of sodium fluoride, potassium fluoride, and cesium fluoride), and alkali metal phosphate (e.g., potassium dihydrogen phosphate, KH)2PO4And/or potassium phosphateK3PO4) One or more of; more preferably, the base is one or more of an alkali metal acetate (e.g., sodium acetate), an alkali metal carbonate (e.g., potassium carbonate and/or cesium carbonate), an alkali metal bicarbonate (e.g., sodium bicarbonate and/or potassium bicarbonate), and an alkali metal phosphate (e.g., potassium phosphate and/or potassium dihydrogen phosphate); further, the base is sodium bicarbonate.
In the preparation method of the para-substituted aryl compound shown in the formula (I), the amount of the base can be the amount conventionally used in such reactions in the field, and preferably, the molar ratio of the aryl sulfonium salt shown in the formula (II) to the base is 1: (1-6), for example, 1: 3.
In the preparation method of the para-substituted aryl compound shown in the formula (I), the boride shown in the formula (III) can be used in an amount which is conventional in the art, and preferably, the molar ratio of the aryl sulfonium salt shown in the formula (II) to the boride shown in the formula (III) is 1: (1-3), for example, 1: 1.5.
In the preparation method of the para-substituted aryl compound shown in the formula (I), the temperature of the coupling reaction can be the conventional temperature of the reaction in the field, and preferably, the temperature of the coupling reaction is 25-150 ℃; for example 25-35 deg.c.
In the preparation method of the para-substituted aryl compound shown in the formula (I), the progress of the coupling reaction can be detected by a monitoring method (such as TLC, HPLC or NMR) which is conventional in the art, and an end point of the reaction is generally determined by disappearance or no longer reaction of the aryl sulfonium salt shown in the formula (II). The time for the coupling reaction may be 1 to 48 hours, for example 12 hours.
The preparation method of the para-substituted aryl compound shown in the formula (I) can further comprise a post-treatment step, wherein the post-treatment step can be a post-treatment conventional in the reaction in the field, such as quenching reaction (for example, quenching reaction by using dichloromethane), filtering (for example, diatomite filtering), removing the solvent and then performing chromatographic separation (for example, separation through a preparation plate).
The preparation method of the para-substituted aryl compound shown in the formula (I) can also comprise the following steps:
in the solvent, aromatic hydrocarbon compounds shown as a formula (IV), sulfonium salt reagent shown as a formula (V), trifluoromethanesulfonic anhydride, trifluoroacetic anhydride and HBF4·OEt2Performing sulfonium salination reaction on one or more of the above to obtain aryl sulfonium salt shown in formula (II);
Figure BDA0002375181170000151
wherein R, X and Y are as defined above.
In the method for preparing the aryl sulfonium salt represented by the formula (II), the solvent may be a conventional solvent for such reactions in the art, and preferably, the solvent is a haloalkane solvent and/or a nitrile solvent, such as dichloromethane or acetonitrile.
In the method for preparing the aryl sulfonium salt shown in the formula (II), the solvent can be used in an amount which is conventional in the field of such reactions, and preferably, the molar volume ratio of the aromatic hydrocarbon compound shown in the formula (IV) to the solvent is 0.01-5.0mol/L, for example 0.2 mol/L.
In the preparation method of the aryl sulfonium salt shown in the formula (II), the trifluoromethanesulfonic anhydride, trifluoroacetic anhydride and HBF4·OEt2One or more of "may be trifluoromethanesulfonic anhydride or trifluoroacetic anhydride, or trifluoroacetic anhydride and HBF4·OEt2Combinations of (a) and (b).
In the preparation method of the aryl sulfonium salt shown in the formula (II), the trifluoromethanesulfonic anhydride, trifluoroacetic anhydride and HBF4·OEt2The amount of one or more of "may be an amount conventionally used in such reactions in the art, and preferably, the aromatic hydrocarbon compound represented by the formula (IV) is reacted with the" trifluoromethanesulfonic anhydride, trifluoroacetic anhydride and HBF4·OEt2Is 1: (1-3), for example, 1: 1.2.
In the method for preparing the aryl sulfonium salt shown in the formula (II), the amount of the sulfonium salt reagent shown in the formula (V) can be the amount conventionally used in such reactions in the field, and preferably, the molar ratio of the aromatic hydrocarbon compound shown in the formula (IV) to the sulfonium salt reagent shown in the formula (V) is 1: (1-3), for example, 1: 1.2.
Preferably, the preparation method of the arylsulfonium salt represented by the formula (II) may be performed under an inert atmosphere, which may be an inert atmosphere commonly used in the art, such as nitrogen or argon.
In the preparation method of the aryl sulfonium salt shown in the formula (II), the temperature of the sulfonium salt reaction can be the conventional temperature of the reaction in the field, and preferably, the temperature of the sulfonium salt reaction is-40-35 ℃; for example, the temperature is raised to 25-35 ℃ for reaction for 50-70min after the reaction is carried out for 10-40min at-40 ℃.
In the preparation method of the aryl sulfonium salt shown in the formula (II), the progress of the sulfonium salination reaction can be detected by a conventional monitoring method in the field (such as TLC, HPLC or NMR), and generally the disappearance or no longer reaction of the aromatic hydrocarbon compound shown in the formula (IV) is taken as a reaction end point. The duration of the sulphonation reaction may be between 1 and 3 hours, for example 1.5 hours.
In the preparation method of the aryl sulfonium salt shown in the formula (II), preferably, the sulfonium salination reaction is directly performed without post-treatment.
The above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention without departing from the common general knowledge in the art.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows:
the method is characterized in that a monosubstituted aromatic hydrocarbon compound and thianthrene-S-oxide are designed to generate aryl sulfonium salt at para position of monosubstituted aromatic hydrocarbon with high selectivity under the action of a reagent, then the aryl sulfonium salt generated in situ by palladium catalysis is subjected to Suzuki-Miyaura coupling reaction with different aryl boric acid reagents, aromatic heterocyclic boric acid reagents and alkenyl borate reagents, and a plurality of monosubstituted aromatic hydrocarbon para-position aryl products, aromatic heterocyclic products and alkenyl products are obtained with high selectivity.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
In the following examples, the yield refers to the isolated yield unless otherwise specified.
In the following examples, the nuclear magnetic yield was determined as follows: after the crude product obtained by the post-treatment is dissolved by deuterated chloroform, 0.1mmol of dibromomethane (7uL) is added as an internal standard, and after nuclear magnetic crude spectrum is carried out, the nuclear magnetic yield of the target product is indicated by taking the characteristic peak integral of hydrogen of the dibromomethane as 1.
Example 1
Figure BDA0002375181170000161
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.5mmol), thianthrene-S-oxide (0.6mmol) and DCM (0.5mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. The solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (DCM/MeOH (20/1)) to give the sulfonium salt 2 a. Wherein the molar ratio (p/o) of the para-substituted product (sulfonium salt 2a) to the ortho-substituted product is 95.3/1.0, and there is no meta-substituted product.
Yield 92% isolated, white solid.1H NMR(400MHz,CDCl3)δ8.55–8.50(m,2H),7.89–7.82(m,4H),7.79–7.73(m,2H),7.24(d,J＝8.4Hz,2H),7.07(d,J＝8.4Hz,2H),2.33(s,3H)；13CNMR(100MHz,CDCl3)δ144.26,136.33,134.87,134.81,131.30,130.25,130.02,127.75,120.75(q,J＝319.0Hz),120.03,118.51,21.16；19F NMR(375MHz,CDCl3)δ-78.53；HRMS(ESI-TOF)m/z Calcd for C19H15S2(M+)307.0610,found:307.0614.
Example 2
(1) Palladium catalyst screening
Figure BDA0002375181170000171
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), palladium catalyst (0.01mmol) (as shown in table 1 below) were added under nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure, and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3k as a white solid, with some unreacted sulfonium salt 2a in some experiments, as shown in Table 1, wherein the yields shown in Table 1 were determined by1H NMR determination (in CH)2Br2As an internal standard), when a ligand is added, the amount of the ligand added is 0.02mmol (e.g., Pd (OAc)2/PPh3In the specification, Pd (OAc)2(0.01mmol) as catalyst, PPh3(0.02mmol) as ligand).
3k：1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.65(d,J＝7.2Hz,2H),7.53(d,J＝7.6Hz,2H),7.30–7.26(m,2H),3.94(s,3H),2.41(s,3H).
TABLE 1
Figure BDA0002375181170000181
(2) Screening for bases
Figure BDA0002375181170000182
Under a nitrogen atmosphere, mono-substituted aromatic hydrocarbon substrate 1a (0.2 mm) was sequentially added to a 25mL Schlenk tubeol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) was added, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Followed by addition of base (0.6mmol) under nitrogen (as shown in Table 2 below), arylboronic acid substrate 4k (0.3mmol), Pd (tBu)3P)2(0.01mmol), acetone (1.0mL) was added, the flask was closed, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure, and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3k as a white solid, with some unreacted sulfonium salt 2a in some experiments, as shown in Table 2, wherein the yields shown in Table 2 were determined by1H NMR determination (in CH)2Br2As an internal standard).
TABLE 2
Figure BDA0002375181170000191
(3) Screening of solvents
Figure BDA0002375181170000192
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Then NaHCO was added under nitrogen atmosphere3(0.6mmol), arylboronic acid substrate 4k (0.3mmol), Pd (tBu)3P)2(0.01mmol), solvent (1.0mL) (as shown in Table 3 below) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure, and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3k as a white solid, with some unreacted sulfonium salt 2a remaining in the experiment, as shown in Table 3, wherein the yields shown in Table 3 were determined by1H NMR determination (in CH)2Br2As an internal standard).
TABLE 3
Figure BDA0002375181170000201
Example 3
Figure BDA0002375181170000202
To a 25mL Schlenk tube under nitrogen was added the mono-substituted arene substrate 1a (0.5mmol), phenoxathiin-10-oxide, DCM (0.5mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. The solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (DCM/MeOH (20/1)) to give the sulfonium salt 2 b. Wherein the molar ratio (p/o) of the para-substituted product (sulfonium salt 2b) to the ortho-substituted product is 76.8/1.0, and there is no meta-substituted product.
Isolated yield 94% as grey solid.1H NMR(400MHz,CDCl3)δ8.16(d,J＝8.4Hz,2H),7.83(ddd,J＝8.4,7.2,1.6Hz,2H),7.65–7.60(m,4H),7.52–7.47(m,2H),7.33(d,J＝8.0Hz,2H),2.35(s,3H)；13C NMR(100MHz,CDCl3)δ151.46,146.10,136.60,132.17,131.81,129.11,127.77,127.46,120.77(q,J＝318.0Hz),120.29,105.97,21.49；19F NMR(375MHz,CDCl3)δ-78.61；HRMS(ESI-TOF)m/z Calcd for C19H15OS(M+)291.0838,found:291.0841.
Example 4
Figure BDA0002375181170000211
To a 25mL Schlenk tube, under a nitrogen atmosphere, were added sequentially mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (i.e., TTSO) (0.24mmol), DCM (1.0mL) and stirred at-40 deg.C. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Sodium bicarbonate (0.6mmol), arylboronic acid substrate 4a (0.3mmol), bis (tri-tert-butyl) were then added under a nitrogen atmosphereButylphosphine) Palladium (0.01mmol), acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc/DCM (50/1/1)) to give 3a (30.5mg) as a colorless liquid in 91% isolated yield.
1H NMR(400MHz,CDCl3)δ7.58(d,J＝7.6Hz,2H),7.49(d,J＝8.0Hz,2H),7.42(t,J＝7.6Hz,2H),7.32(t,J＝7.2Hz,2H),7.26–7.23(m,2H),2.40(s,3H).
Example 5
Figure BDA0002375181170000212
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4b (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give colorless crystals 3b (31.0mg) in 85% yield.
3b：1H NMR(400MHz,CDCl3)δ7.48(d,J＝8.0Hz,4H),7.23(d,J＝8.4Hz,4H),2.39(s,6H).
Example 6
Figure BDA0002375181170000221
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Followed by addition of carbon under nitrogen atmosphereSodium hydrogen carbonate (0.6mmol), arylboronic acid substrate 4c (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol), acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate isolation (hexane/EtOAc (50/1)) to afford 3c (43.9mg) as a white solid in 98% yield.
3c：1H NMR(400MHz,CDCl3)δ7.54–7.43(m,6H),7.25–7.22(m,2H),2.38(s,3H),1.36(s,9H).
Example 7
Figure BDA0002375181170000222
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 2d (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (9/1)) to give 3d (47.7mg) as a white solid in 97% yield.
3d：1H NM0R(400MHz,CDCl3)δ7.66–7.61(m,6H),7.54(d,J＝8.0Hz,2H),7.45(t,J＝7.4Hz,2H),7.35(t,J＝7.4Hz,1H),7.27–7.23(m,2H),2.40(s,3H).
Example 8
Figure BDA0002375181170000231
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2O (0.24mmol), and then stirred at-40 ℃ for 30 minutesThen, the mixture was stirred at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4e (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 3e (46.0mg) as a white solid in 96% yield.
3e：1H NMR(400MHz,CDCl3)δ7.60–7.55(m,4H),7.50(d,J＝8.0Hz,2H),7.24(d,J＝7.6Hz,2H),2.39(s,3H),0.30(s,9H).
Example 9
Figure BDA0002375181170000232
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4f (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc/DCM (50/1/1)) to afford 3f (33.0mg) as a white solid in 83% yield.
3f：1H NMR(400MHz,CDCl3)δ7.51(d,J＝8.8Hz,2H),7.45(d,J＝8.0Hz,2H),7.24–7.20(m,2H),6.96(d,J＝8.8Hz,1H),3.84(s,3H),2.38(s,3H).
Example 10
Figure BDA0002375181170000241
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), 4g (0.3mmol) of an arylboronic acid substrate and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc/DCM (50/1/1)) to give 3g (40.0mg) of a pale yellow solid in 93% yield.
3g：1H NMR(400MHz,CDCl3)δ7.56–7.48(m,4H),7.37–7.33(m,2H),7.29–7.25(m,2H),2.55(s,3H),2.42(s,3H).
Example 11
Figure BDA0002375181170000242
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), an arylboronic acid substrate (4 h) (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give a white solid for 3h (42.0mg) in 91% yield.
3h：1H NMR(400MHz,CDCl3)δ7.55–7.50(m,2H),7.44(d,J＝8.4Hz,2H),7.24(d,J＝8.0Hz,2H),7.14–7.08(m,2H),2.39(s,3H).
Example 12
Figure BDA0002375181170000251
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4i (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc/DCM (100/1/1)) to give 3i (37.5mg) as a white solid in 93% yield.
3i：1H NMR(400MHz,CDCl3)δ7.50(d,J＝8.4Hz,2H),7.45(d,J＝8.0Hz,2H),7.39(d,J＝8.4Hz,2H),7.26–7.24(m,2H),2.40(s,3H).
Example 13
Figure BDA0002375181170000252
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4j (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (50/1)) to afford 3j (38.4mg) as a white solid in 91% yield.
3j：1H NMR(400MHz,CDCl3)δ8.01(d,J＝8.8Hz,2H),7.66(d,J＝8.4Hz,2H),7.53(d,J＝8.4Hz,2H),7.30–7.26(m,2H).,2.62(s,3H),2.41(s,3H).
Example 14
Figure BDA0002375181170000261
Under the atmosphere of nitrogen, the nitrogen gas is introduced into the reactor,to a 25mL Schlenk tube were added in sequence mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.005mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours by screwing the cap. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/EtOAc (20/1)) to afford 3k (45.0mg) as a white solid in 99% yield.
Example 15
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.005mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours by screwing the cap. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/EtOAc (20/1)) to afford 3k (45.0mg) as a white solid in 99% yield.
Example 16
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.005mmol) and DMF (1.0mL) were added under nitrogen atmosphere, the flask was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure, and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3k as a white solid,the yield is 85 percent; unreacted sulfonium salt 2a, yield 14%.
Example 17
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.005mmol) and DMA (1.0mL) were added under a nitrogen atmosphere, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/EtOAc (20/1)) to afford 3k as a white solid in 98% yield.
Example 18
Figure BDA0002375181170000271
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), 4l (0.3mmol) of an arylboronic acid substrate, and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 3l (49.0mg) of a white solid in 97% yield.
3l：1H NMR(400MHz,CDCl3)δ7.59–7.55(m,2H),7.47–7.43(m,2H),7.28–7.23(m,4H),2.40(s,3H).
Example 19
Figure BDA0002375181170000272
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4m (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours by screwing the cap. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3m (42.5mg) as a white solid in 90% yield.
3m：1H NMR(400MHz,CDCl3)δ7.68(s,4H),7.50(d,J＝8.4Hz,2H),7.28(d,J＝7.6Hz,2H),2.42(s,3H).
Example 20
Figure BDA0002375181170000281
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 2n (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc/DCM (100/1/1)) to give 3n (35.0mg) as colorless crystals in 96% yield.
3n：1H NMR(400MHz,CDCl3)δ7.26–7.21(m,8H),2.40(s,3H),2.28(s,3H).
Example 21
Figure BDA0002375181170000282
Under nitrogen atmosphere, inA25 mL Schlenk tube was charged with mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4o (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 3o (33.0mg) as a white solid in 82% yield.
3o：1H NMR(400MHz,CDCl3)δ7.45(d,J＝8.0Hz,1H),7.35–7.20(m,7H),2.40(s,3H).
Example 22
Figure BDA0002375181170000291
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4p (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc/DCM (50/1/1)) to afford 3p as a white solid (35.2mg) in 89% yield.
3p：1H NMR(400MHz,CDCl3)δ7.49(d,J＝8.4Hz,2H),7.34(t,J＝8.0Hz,1H),7.26–7.23(m,2H),7.18–7.14(m,1H),7.12–7.09(m,1H),6.89–6.84(m,1H),3.86(s,3H),2.39(s,3H).
Example 23
Figure BDA0002375181170000301
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4q (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to afford 3q (44.0mg) as a white solid in 97% yield.
3q：1H NMR(400MHz,CDCl3)δ8.27(s,1H),7.99(d,J＝7.6Hz,1H),7.77(d,J＝7.6Hz,1H),7.55–7.46(m,3H),7.29–7.26(m,2H),3.94(s,3H),2.41(s,3H).
Example 24
Figure BDA0002375181170000302
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4r (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (50/1)) to afford 3r (35.6mg) as a yellow solid in 83% yield.
3r：1H NMR(400MHz,CDCl3)δ8.43(t,J＝1.8Hz,1H),8.18–8.14(m,1H),7.91–7.87(m,1H),7.58(t,J＝8.0Hz,1H),7.52(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),2.42(s,3H).
Example 25
Figure BDA0002375181170000311
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4s (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 3s (32.0mg) as a white solid in 74% yield.
3s：1H NMR(400MHz,CDCl3)δ7.41(d,J＝8.0Hz,2H),7.21(d,J＝7.6Hz,2H),7.06–7.01(m,2H),6.86(d,J＝8.4Hz,1H),5.98(s,2H),2.38(s,3H).
Example 26
Figure BDA0002375181170000312
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4t (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 3t (38.0mg) as a white solid in 87% yield.
3t：1H NMR(400MHz,CDCl3)δ8.02(s,1H),7.92–7.83(m,3H),7.76–7.72(m,1H),7.63(d,J＝8.0Hz,2H),7.52–7.44(m,2H),7.30(d,J＝8.0Hz,2H),2.42(s,3H).
Example 27
Figure BDA0002375181170000321
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4u (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc/DCM (100/1/1)) to afford 3u (55.0mg) as a white solid in 91% yield.
3u：1H NMR(400MHz,CDCl3)δ7.99(s,2H),7.82(s,1H),7.51(d,J＝8.0Hz,2H),7.31(d,J＝8.0Hz,2H),2.42(s,3H).
Example 28
Figure BDA0002375181170000322
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4v (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the cap was screwed, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc/DCM (25/1/1)) to afford 3v (50.0mg) as a pale yellow solid in 97% yield.
3v：1H NMR(400MHz,CDCl3)δ7.45(d,J＝8.0Hz,2H),7.24(d,J＝8.0Hz,2H),6.76(s,2H),3.92(s,6H),3.89(s,3H),2.40(s,3H).
Example 29
Figure BDA0002375181170000331
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4w (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the cap was screwed, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 3w (44.0mg) as a white solid in 85% yield.
3w：1H NMR(400MHz,CDCl3)δ7.33–7.28(m,4H),2.42(s,3H).
Example 30
Figure BDA0002375181170000332
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4aa (0.3mmol), bis (tri-tert-butylphosphine) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane) to give 3aa (26.9mg) as a white solid in 85% yield.
3aa：1H NMR(400MHz,CDCl3)δ7.69(s,1H),7.46(t,J＝1.6Hz,1H),7.38(d,J＝8.0Hz,2H),7.18(d,J＝7.6Hz,2H),6.70–6.68(m,1H),2.36(s,4H).
Example 31
Figure BDA0002375181170000341
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4ab (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (50/1)) to give 3ab (34.5mg) as a white solid in 99% yield.
3ab:1H NMR(400MHz,CDCl3)δ7.49(d,J＝8.0Hz,2H),7.41(t,J＝2.2Hz,1H),7.37(d,J＝2.0Hz,2H),7.21(d,J＝8.0Hz,2H),2.37(s,3H).
Example 32
Figure BDA0002375181170000342
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4ac (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 4ac (34.5mg) as a white solid in 84% yield.
3ac:1H NMR(400MHz,CDCl3)δ7.83(d,J＝8.0Hz,1H),7.77(s,1H),7.54(d,J＝8.0Hz,3H),7.36–7.28(m,4H),2.42(s,3H).
Example 33
Figure BDA0002375181170000351
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4ad (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 3ad (42.0mg) as a white solid in 94% yield.
3ad:1H NMR(400MHz,CDCl3)δ7.82(d,J＝8.0Hz,1H),7.75(d,J＝8.0Hz,1H),7.61(d,J＝8.0Hz,2H),7.50(s,1H),7.36–7.27(m,2H),7.23(d,J＝8.0Hz,2H),2.39(s,3H).
Example 34
Figure BDA0002375181170000352
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4ae (0.3mmol), bis (tri-tert-butylphosphine) palladium (0.02mmol) were added under nitrogen, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (1/1)) to give 3ae (36.0mg) as a white solid in 89% yield.
3ae:1H NMR(400MHz,CDCl3)δ8.95(dd,J＝4.0,1.6Hz,1H),8.19(dd,J＝8.4,1.6Hz,1H),7.80(dd,J＝8.4,1.6Hz,1H),7.72(dd,J＝7.2,1.6Hz,1H),7.61–7.56(m,3H),7.40(dd,J＝8.4,4.0Hz,1H),7.31(d,J＝7.6Hz,2H),2.43(s,3H).
Example 35
Figure BDA0002375181170000361
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4af (0.3mmol), bis (tri-tert-butylphosphine) palladium (0.02mmol) were added under nitrogen, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (1/1)) to give 3af (32.0mg) as a white solid in 73% yield.
3af:1H NMR(400MHz,CDCl3)δ9.18(d,J＝2.4Hz,1H),8.29(d,J＝2.0Hz,1H),8.13(d,J＝8.4Hz,1H),7.88(d,J＝8.0Hz,1H),7.73–7.68(m,1H),7.63(d,J＝8.4Hz,2H),7.58(t,J＝7.4Hz,1H),7.34(d,J＝8.0Hz,2H),2.44(s,3H).
Example 36
Figure BDA0002375181170000362
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4ag (0.3mmol), bis (tri-tert-butylphosphine) palladium (0.02mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the reaction was stirred at 50 ℃ for 12 hours by screwing the cap. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (1/5)) to give 3ag (25.0mg) as a white solid in 75% yield.
3ag:1H NMR(400MHz,CDCl3)δ8.84(s,1H),8.57(d,J＝4.8Hz,1H),7.87–7.84(m,1H),7.49(d,J＝8.0Hz,2H),7.35(dd,J＝7.6,4.8Hz,1H),7.29(d,J＝8.0Hz,2H),2.41(s,3H).
Example 37
Figure BDA0002375181170000371
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4ah (0.3mmol), bis (tri-tert-butylphosphine) palladium (0.02mmol) were added under nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/DCM (1/1)) to give 3ah (37.4mg) as a pale yellow solid in 92% yield.
3ah:1H NMR(400MHz,CDCl3)δ8.38(dd,J＝4.8,2.0Hz,1H),7.66(dd,J＝7.6,2.0Hz,1H),7.35(d,J＝8.0Hz,2H),7.31–7.28(m,3H),2.42(s,3H)；13C NMR(100MHz,CDCl3)δ149.77,148.13,139.61,138.24,136.97,134.56,129.13,129.04,122.49,21.25.HRMS(ESI-TOF)m/z Calcd for C12H11ClN[M+H]+:204.0575,found:204.0575.
Example 38
Figure BDA0002375181170000372
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4ai (0.3mmol), bis (tri-tert-butylphosphine) palladium (0.02mmol) were added under nitrogen, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure, and the crude product was isolated and purified on a prep. plate (hexane/DCM (1/1)) to give 3ai (35.0mg) as a pale yellow solid in 93% yield.
3ai:1H NMR(400MHz,CDCl3)δ8.18–8.16(m,1H),7.88–7.83(m,1H),7.47(dd,J＝8.0,1.4Hz,2H),7.29–7.24(m,3H),2.41(s,3H)；13C NMR(100MHz,CDCl3)δ160.44(d,J＝239.0Hz),145.94(d,J＝14.0Hz),140.45(d,J＝5.0Hz),138.42,130.93(d,J＝5.0Hz),129.42,128.63(d,J＝3.0Hz),123.88(d,J＝28.0Hz),121.75(d,J＝4.0Hz),21.20；19F NMR(375MHz,CDCl3)δ-72.51.HRMS(ESI-TOF)m/z Calcd for C12H11FN[M+H]+188.0870,found:188.0869.
Example 39
Figure BDA0002375181170000381
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4aj (0.3mmol), bis (tri-tert-butylphosphine) palladium (0.02mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (9/1)) to give 3aj (39.0mg) as a white solid in 95% yield.
3ai:1H NMR(400MHz,CDCl3)δ7.95(dd,J＝17.2,8.0Hz,1H),7.42(d,J＝7.6Hz,2H),7.28(d,J＝8.0Hz,2H),6.90(dd,J＝8.0,2.8Hz,1H),2.41(s,3H)；13C NMR(100MHz,CDCl3)δ160.33(dd,J＝231.3,13.1Hz),157.74(dd,J＝234.5,13.7Hz),144.73(dd,J＝7.0,5.0Hz),138.50,129.92(d,J＝4.8Hz),129.51,128.49(d,J＝2.9Hz),120.61(dd,J＝25.6,5.9Hz),106.39(ddd,J＝34.5,5.7,1.5Hz),21.19；19F NMR(375MHz,CDCl3)δ-71.19,-71.71.HRMS(EI)m/z Calcd for C12H9F2N(M+)205.0698,found:205.0696.
Example 40
Figure BDA0002375181170000391
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), an alkenylboronic acid ester substrate 6a (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give 5a (28.0mg) as a colorless liquid in 72% yield.
5a:1H NMR(400MHz,CDCl3)δ7.36–7.29(m,5H),7.24(d,J＝8.0Hz,2H),7.14(d,J＝8.0Hz,2H),5.43(d,J＝1.2Hz,1H),5.40(d,J＝1.2Hz,1H),2.37(s,1H).
EXAMPLE 41
Figure BDA0002375181170000392
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), an alkenylboronic acid ester substrate 6b (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give 5b (30.0mg) as a colorless liquid in 79% yield.
5b:1H NMR(400MHz,CDCl3)δ7.66(d,J＝16.0Hz,1H),7.42(d,J＝8.0Hz,2H),7.19(d,J＝8.0Hz,2H),6.39(d,J＝16.0Hz,1H),4.26(q,J＝6.8Hz,2H),2.37(s,3H),1.33(t,J＝7.2Hz,3H).
Example 42
Figure BDA0002375181170000401
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), an alkenyl borate substrate 6c (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give 5c (22.0mg) as a colorless liquid in 83% yield.
5c:1H NMR(400MHz,CDCl3)δ7.14–7.04(m,4H),6.19(s,1H),2.40–2.35(m,2H),2.33(s,3H),2.27–2.22(m,2H),1.66–1.58(m,4H),1.55–1.50(m,2H).
Example 43
Figure BDA0002375181170000402
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), an alkenylboronic acid ester substrate 6d (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give 5d (22.0mg) as a colorless liquid in 76% yield.
5d:1H NMR(400MHz,CDCl3)δ7.12(s,4H),6.23(s,1H),2.33(s,3H),1.89(s,3H),1.85(s,3H).
Example 44
Figure BDA0002375181170000411
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), alkenylboronic acid ester substrate 6e (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give 5e (18.0mg) as a colorless liquid in 57% yield.
5e:1H NMR(400MHz,CDCl3)δ7.33(d,J＝8.4Hz,2H),7.11(d,J＝8.0Hz,2H),6.13–6.11(m,1H),2.71–2.67(m,2H),2.54–2.49(m,2H),2.33(s,3H),2.04–1.97(m,2H).
Example 45
Figure BDA0002375181170000412
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), an alkenylboronic acid ester substrate 6f (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 5f (31.0mg) as a colorless liquid in 90% yield.
5f:1H NMR(400MHz,CDCl3)δ7.27(d,J＝8.0Hz,2H),7.11(d,J＝8.0Hz,2H),6.10–6.05(m,1H),2.42–2.36(m,2H),2.32(s,3H),2.22–2.16(m,2H),1.81–1.73(m,2H),1.68–1.62(m,2H).
Example 46
Figure BDA0002375181170000421
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), 6g (0.3mmol) of an alkenyl borate substrate and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (50/1)) to give 5g (29.0mg) of a white solid in 63% yield.
5g:1H NMR(400MHz,CDCl3)δ7.29(d,J＝8.0Hz,2H),7.11(d,J＝8.0Hz,2H),5.96–5.93(m,1H),4.02(s,4H),2.67–2.63(m,2H),2.48–2.44(m,2H),2.33(s,3H),1.92(t,J＝6.4Hz,2H).
Example 47
Figure BDA0002375181170000422
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), alkenylboronic acid ester substrate (6 h (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give a colorless liquid 5h (20.0mg) in 57% yield.
5h:1H NMR(400MHz,CDCl3)δ7.29(d,J＝8.0Hz,2H),7.15(d,J＝8.0Hz,2H),6.10–6.07(m,1H),4.32(q,J＝2.8Hz,2H),3.93(t,J＝5.2Hz,2H),2.53–2.49(m,2H),2.35(s,3H).
Example 48
Figure BDA0002375181170000431
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), alkenylboronic acid ester substrate 6i (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate isolation (hexane/EtOAc (10/1)) to give 5i (27.0mg) as a white solid in 50% yield.
5i:1H NMR(400MHz,CDCl3)δ7.27(d,J＝8.4Hz,2H),7.14(d,J＝8.0Hz,2H),5.99(s,1H),4.06(s,2H),3.63(t,J＝5.6Hz,2H),2.51(s,2H),2.34(s,3H),1.49(s,9H).
Example 49
Figure BDA0002375181170000432
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), an alkenylboronic acid ester substrate 6j (0.3mmol) and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (MeOH/DCM (1/20)) to give 5j (20.0mg) as a white solid in 53% yield.
5j:1H NMR(400MHz,CDCl3)δ7.28(d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,2H),6.02–6.00(m,1H),3.13(d,J＝3.2Hz,2H),2.69(t,J＝5.6Hz,2H),2.62–2.58(m,2H),2.43(s,3H),2.33(s,3H)；13C NMR(100MHz,CDCl3)δ138.01,136.72,134.57,128.97,124.82,120.67,54.91,52.28,45.62,28.03,21.04.HRMS(EI)m/z Calcd for C13H17N(M+)187.1355,found:187.1356.
Example 50
Figure BDA0002375181170000441
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 8a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (10/1)) to afford 7a (44.0mg) as a white solid in 92% yield.
7a:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.65(d,J＝8.0Hz,2H),7.56(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),3.94(s,3H),2.71(q,J＝7.6Hz,2H),1.28(t,J＝7.6Hz,3H)；13C NMR(100MHz,CDCl3)δ167.05,145.58,144.44,137.31,130.05,128.56,128.45,127.18,126.80,52.07,28.54,15.52.HRMS(EI)m/z Calcd for C16H16O2(M+)240.1145,found:240.1142.
Example 51
Figure BDA0002375181170000451
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 8b (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to afford 7b as a white solid (47.3mg) in 93% yield.
7b:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.65(d,J＝8.8Hz,2H),7.56(d,J＝8.0Hz,2H),7.33(d,J＝8.4Hz,2H),3.93(s,3H),3.00–2.93(m,1H),1.29(d,J＝6.8Hz,6H)；13C NMR(100MHz,CDCl3)δ167.04,149.04,145.55,137.43,130.04,128.54,127.17,127.00,126.80,52.07,33.83,23.93.HRMS(EI)m/z Calcd for C17H18O2(M+)254.1301,found:254.1298.
Example 52
Figure BDA0002375181170000452
To a 25mL Schlenk tube under a nitrogen atmosphere were added the mono-substituted aromatic substrate 8c (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate isolation (hexane/EtOAc (20/1)) to afford 7c as a white solid (53.0mg) in 99% yield.
7c:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.65(d,J＝8.4Hz,2H),7.57(d,J＝8.4Hz,2H),7.49(d,J＝8.4Hz,2H),3.93(s,3H),1.36(s,9H).；13C NMR(100MHz,CDCl3)δ167.03,151.31,145.44,137.01,130.05,128.58,126.89,126.80,125.87,52.06,34.60,31.29.HRMS(EI)m/z Calcd for C18H20O2(M+)268.1458,found:268.1460.
Example 53
Figure BDA0002375181170000461
To a 25mL Schlenk tube under a nitrogen atmosphere were added sequentially the mono-substituted aromatic substrate 8d (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate isolation (hexane/EtOAc (20/1)) to afford 7d (57.6mg) as a white solid in 98% yield.
7d:1H NMR(400MHz,CDCl3)δ8.08(d,J＝8.4Hz,2H),7.64(d,J＝8.4Hz,2H),7.55(d,J＝8.4Hz,2H),7.30(d,J＝8.0Hz,2H),3.93(s,3H),2.58–2.52(m,1H),1.93–1.83(m,4H),1.77(d,J＝12.8Hz,1H),1.51–1.36(m,4H),1.32–1.25(m,1H)；13C NMR(100MHz,CDCl3)δ167.05,148.28,145.58,137.43,130.04,128.55,127.41,127.15,126.80,52.07,44.28,34.40,26.85,26.12.HRMS(ESI-TOF)m/z Calcd for C20H22NaO2[M+Na]+317.1512,found:317.1517.
Example 54
Figure BDA0002375181170000462
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 8e (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to afford 7e (51.0mg) as a white solid in 84% yield.
7e:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.64(d,J＝8.4Hz,2H),7.55(d,J＝8.0Hz,2H),7.33–7.27(m,4H),7.23–7.18(m,3H),4.03(s,2H),3.93(s,3H).
Example 55
Figure BDA0002375181170000471
To a 25mL Schlenk tube under a nitrogen atmosphere were added the mono-substituted aromatic substrate 8f (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.02mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to afford 7f as a white solid (46.0mg) in 80% yield.
7f:1H NMR(400MHz,CDCl3)δ8.13(d,J＝8.0Hz,2H),7.74–7.67(m,6H),7.65(d,J＝7.2Hz,2H),7.47(t,J＝7.6Hz,2H),7.38(t,J＝7.6Hz,1H),3.95(s,3H).
Example 56
Figure BDA0002375181170000481
To a 25mL Schlenk tube under a nitrogen atmosphere were added 8g (0.2mmol) of the mono-substituted aromatic substrate, followed by thianthrene-S-oxide (0.24mmol), and DCM (1.0mL) followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (1/1)) to give 7g (39.8mg) of a white solid in 81% yield.
7g:1H NMR(400MHz,CDCl3)δ8.07(d,J＝8.0Hz,2H),7.61(d,J＝8.4Hz,2H),7.57(d,J＝8.8Hz,2H),6.99(d,J＝8.4Hz,2H),3.93(s,3H),3.86(s,3H).
Example 57
Figure BDA0002375181170000482
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate for 8h (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.02mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 7h (43.0mg) as a white solid in 80% yield.
7h:1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.8Hz,2H),7.63(dd,J＝8.8,1.6Hz,4H),7.19(d,J＝8.8Hz,2H),3.94(s,3H),2.33(s,3H)；13C NMR(100MHz,CDCl3)δ169.45,166.93,150.72,144.71,137.73,130.13,128.98,128.34,126.99,122.07,52.14,21.14.HRMS(ESI-TOF)m/z Calcd for C16H15O4[M+H]+271.0965,found:271.0969.
Example 58
Figure BDA0002375181170000491
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8i (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.02mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (3/1)) to give 7i (50.0mg) as a white solid in 82% yield.
7i:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.63(d,J＝8.4Hz,2H),7.59(d,J＝8.8Hz,2H),7.37(t,J＝8.4Hz,2H),7.14(t,J＝7.6Hz,1H),7.08(t,J＝8.4Hz,4H),3.94(s,3H)；13C NMR(100MHz,CDCl3)δ166.97,157.68,156.78,144.90,134.80,130.12,129.84,128.60,126.68,123.63,119.21,118.95,52.09.HRMS(ESI-TOF)m/z Calcd forC20H16NaO3[M+Na]+327.0992,found:327.0999.
Example 59
Figure BDA0002375181170000492
To a 25mL Schlenk tube under nitrogen was added sequentially the monosubstituted aromatic substrate 8j (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.02mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (10/1)) to afford 7j (34.7mg) as a white solid in 62% yield.
7j:H NMR(400MHz,CDCl3)δ8.11(d,J＝8.4Hz,2H),7.62(dd,J＝8.4,2.4Hz,4H),7.22(d,J＝8.8Hz,2H),6.56(t,J＝73.8Hz,1H),3.94(s,3H)；13C NMR(100MHz,CDCl3)δ166.88,151.16(d,J＝2.8Hz),144.39,137.29,130.18,129.08,128.69,126.90,119.95,115.78(t,J＝258.8Hz),52.16.19F NMR(375MHz,CDCl3)δ-81.34,-81.54.HRMS(EI)m/zCalcd for C15H12F2O3(M+)278.0749,found:278.0751.
Example 60
Figure BDA0002375181170000501
To a 25mL Schlenk tube under nitrogen was added sequentially 8k (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate isolation (hexane/EtOAc (20/1)) to give 7k (14.0mg) as a white solid in 24% yield.
7k:1H NMR(400MHz,CDCl3)δ8.11(d,J＝8.8Hz,2H),7.66–7.61(m,4H),7.31(d,J＝8.0Hz,2H),3.95(s,3H)；13C NMR(100MHz,CDCl3)δ166.82,149.21(d,J＝1.6Hz),144.13,138.68,130.19,129.26,128.65,127.00,121.33,120.44(q,J＝255.8Hz),52.20.19F NMR(375MHz,CDCl3)δ-58.31.HRMS(EI)m/z Calcd for C15H11F3O3(M+)296.0655,found:296.0658.
Example 61
Figure BDA0002375181170000511
To a 25mL Schlenk tube under a nitrogen atmosphere were added 8l (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (1/1)) to give 7l (28.0mg) of a white solid in 47% yield.
7l:1H NMR(400MHz,CDCl3)δ8.07(d,J＝8.0Hz,2H),7.62(d,J＝8.0Hz,2H),7.57(d,J＝8.8Hz,2H),6.99(d,J＝8.4Hz,2H),3.93(s,3H),3.89(t,J＝4.0Hz,4H),3.23(t,J＝4.0Hz,2H).13C NMR(100MHz,CDCl3)δ167.10,151.16,145.16,131.00,130.08,127.98,126.15,115.57,66.80,52.04,48.84.HRMS(EI)m/z Calcd for C18H19NO3(M+)297.1361,found:297.1359.
Example 62
Figure BDA0002375181170000512
To a 25mL Schlenk tube under a nitrogen atmosphere were added sequentially 8m (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (DCM) to give 7m (43.0mg) as a white solid in 73% yield.
7m:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.0Hz,2H),7.73(d,J＝8.8Hz,2H),7.67–7.62(m,4H),3.95–3.88(m,5H),2.65(t,J＝7.6Hz,2H),2.24–2.16(m,2H)；13C NMR(100MHz,CDCl3)δ174.36,166.97,144.82,139.44,135.77,130.11,128.69,127.57,126.67,120.07,52.10,48.66,32.75,17.96.HRMS(ESI-TOF)m/z Calcd for C18H18NO3[M+H]+296.1281,found:296.1285.
Example 63
Figure BDA0002375181170000521
To a 25mL Schlenk tube under nitrogen was added sequentially the monosubstituted aromatic substrate 8n (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by prep. plate separation (DCM) to give 7n (36.2mg) as a white solid in 64% yield.
7n:1H NMR(400MHz,CDCl3)δ8.13(d,J＝8.4Hz,2H),7.67(dd,J＝8.0,2.0Hz,4H),7.30(d,J＝8.4Hz,2H),3.95(s,3H),3.31(s,3H),1.94(s,3H)；13C NMR(100MHz,CDCl3)δ170.50,166.82,144.45,144.27,139.41,130.20,129.31,128.53,127.51,126.97,52.18,37.16,22.48HRMS(ESI-TOF)m/z Calcd for C17H18NO3[M+H]+284.1281,found:284.1288.
Example 64
Figure BDA0002375181170000522
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8o (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 7o (30.0mg) as a white solid in 65% yield.
7o:1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.4Hz,2H),7.63–7.56(m,4H),7.15(t,J＝8.8Hz,2H),3.94(s,3H)；13C NMR(100MHz,CDCl3)δ166.91,164.16,161.70,144.58,136.11(d,J＝4.0Hz),130.15,128.91(d,J＝8.0Hz),126.87,115.86(d,J＝21.0Hz),52.14.19FNMR(375MHz,CDCl3)δ-114.75.HRMS(EI)m/z Calcd for C14H11FO2(M+)230.0738,found:230.0737.
Example 65
Figure BDA0002375181170000531
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8p (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to afford 7p (16.0mg) as a white solid in 33% yield.
7p:1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.0Hz,2H),7.62(d,J＝8.4Hz,2H),7.55(d,J＝8.4Hz,2H),7.43(d,J＝8.4Hz,2H),3.94(s,3H).
Example 66
Figure BDA0002375181170000541
To a 25mL Schlenk tube under a nitrogen atmosphere were added sequentially 8q (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (10/1)) to afford 7q (30.7mg) as a white solid in 54% yield.
7q:1H NMR(400MHz,CDCl3)δ8.11(d,J＝8.4Hz,2H),7.65(d,J＝8.4Hz,2H),7.62(d,J＝8.0Hz,2H),7.46(d,J＝8.0Hz,2H),5.16(s,2H),3.94(s,3H),2.13(s,3H)；13C NMR(100MHz,CDCl3)δ170.86,166.92,145.02,139.96,135.89,130.12,129.06,128.82,127.45,127.00,65.88,52.13,21.00.HRMS(EI)m/z Calcd for C17H16O4(M+)284.1043,found:284.1046.
Example 67
Figure BDA0002375181170000542
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8r (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (3/2)) to give 7r (37.0mg) as a white solid in 51% yield.
7r:1H NMR(400MHz,CDCl3)δ8.08(d,J＝8.4Hz,2H),7.88–7.84(m,2H),7.74–7.69(m,2H),7.62-7.52(m,6H),4.90(s,2H),3.93(s,3H)；13C NMR(100MHz,CDCl3)δ168.02,166.93,145.05,139.55,136.29,134.04,132.07,130.07,129.18,128.94,127.56,126.96,123.39,52.11,41.24.HRMS(EI)m/z Calcd for C23H17NO4(M+)371.1156,found:371.1152.
Example 68
Figure BDA0002375181170000551
To a 25mL Schlenk tube under nitrogen was added sequentially 8S (0.2mmol) of the mono-substituted aromatic substrate, 0.24mmol of thianthrene-S-oxide, DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by prep. plate separation (DCM) to give 7s (51.0mg) as a white solid in 66% yield.
7s:1H NMR(400MHz,CDCl3)δ8.08(d,J＝8.4Hz,2H),7.85–7.80(m,2H),7.73–7.68(m,2H),7.63(d,J＝8.4Hz,2H),7.55(d,J＝8.0Hz,2H),7.35(d,J＝8.0Hz,2H),3.99–3.91(m,5H),3.05(t,J＝8.0Hz,2H)；13C NMR(100MHz,CDCl3)δ168.14,166.97,145.21,138.26,138.10,133.93,132.02,130.04,129.42,128.74,127.37,126.83,123.23,52.08,39.07,34.22.HRMS(EI)m/z Calcd for C24H20NO4[M+H]+386.1387,found:386.1389.
Example 69
Figure BDA0002375181170000552
To a 25mL Schlenk tube under nitrogen was added 8t (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol) and DCM (0.2mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (1/1)) to give 7t (78.0mg) as a white solid in 97% yield.
7t:1H NMR(400MHz,CDCl3)δ8.07(d,J＝8.4Hz,2H),7.84–7.78(m,2H),7.70–7.65(m,2H),7.59(d,J＝8.0Hz,2H),7.49(d,J＝8.4Hz,2H),7.28(d,J＝8.0Hz,2H),3.93(s,3H),3.77(t,J＝7.2Hz,2H),2.74(t,J＝7.8Hz,2H),2.12–2.03(m,2H)；13C NMR(100MHz,CDCl3)δ168.36,166.97,145.32,141.16,137.56,133.83,132.04,129.98,128.84,128.58,127.17,126.75,123.09,52.04,37.72,32.80,29.54.HRMS(EI)m/z Calcd for C25H21NO4(M+)399.1471,found:399.1465.
Example 70
Figure BDA0002375181170000561
To a 25mL Schlenk tube under nitrogen was added sequentially 8u (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to afford 7u (39.0mg) as a white solid in 68% yield.
7u:1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.4Hz,2H),7.65(d,J＝8.4Hz,2H),7.57(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),3.94(s,3H),3.56(t,J＝6.4Hz,2H),2.84(t,J＝7.4Hz,2H),2.16–2.09(m,2H)；13C NMR(100MHz,CDCl3)δ166.98,145.32,140.83,137.85,130.08,129.12,128.72,127.33,126.81,52.08,44.13,33.88,32.38.HRMS(EI)m/z Calcdfor C17H17ClO2(M+)288.0912,found:288.0914.
Example 71
Figure BDA0002375181170000571
To a 25mL Schlenk tube under nitrogen was added sequentially 8v (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc (10/1)) to afford 7v (47.0mg) as a white solid in 87% yield.
7v:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.65(d,J＝8.4Hz,2H),7.56(d,J＝8.4Hz,2H),7.32(d,J＝8.4Hz,2H),3.94(s,3H),3.65(t,J＝7.2Hz,2H),3.38(s,3H),2.94(t,J＝7.2Hz,2H)；13C NMR(100MHz,CDCl3)δ167.00,145.44,139.20,137.90,130.05,129.41,128.67,127.23,126.83,73.38,58.71,52.09,35.84.HRMS(ESI-TOF)m/zCalcd for C17H19O3[M+H]+271.1329,found:271.1335.
Example 72
Figure BDA0002375181170000572
To a 25mL Schlenk tube under nitrogen was added sequentially 8w (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.8mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of 1M HCl (5.0mL), the organic phase was separated, the aqueous phase was extracted with DCM, the organic phases were combined, the solvent was spun off under reduced pressure, and the crude product was isolated and purified by prep. plate separation (DCM/MeOH (20/1)) to afford 7w (46.0mg) as a white solid in 85% yield.
7w:1H NMR(400MHz,(CD3)2SO)δ8.02(d,J＝8.4Hz,2H),7.81(d,J＝8.4Hz,2H),7.66(d,J＝8.4Hz,2H),7.36(d,J＝8.0Hz,2H),3.87(s,3H),2.87(t,J＝7.2Hz,2H),2.58–2.53(m,2H).13C NMR(100MHz,(CD3)2SO)δ174.39,166.59,145.07,142.03,136.98,130.30,129.55,128.68,127.39,127.23,52.67,35.83,31.22.HRMS(ESI-TOF)m/z Calcd forC17H15O4[M-H]-283.0976,found:283.0981.
Example 73
Figure BDA0002375181170000581
To a 25mL Schlenk tube under nitrogen was added sequentially 8X (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (10/1)) to afford 7X (40.0mg) as a white solid in 68% yield.
7x:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.0Hz,2H),7.64(d,J＝8.0Hz,2H),7.56(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),3.94(s,3H),3.69(s,3H),3.01(t,J＝7.8Hz,2H),2.68(t,J＝7.8Hz,2H).13C NMR(100MHz,CDCl3)δ173.21,167.00,145.32,140.65,138.00,130.08,128.88,128.74,127.37,126.84,52.10,51.68,35.52,30.55.HRMS(EI)m/zCalcd for C18H18O4(M+)298.1203,found:298.1200.
Example 74
Figure BDA0002375181170000591
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8y (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.8mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of 1M HCl (5.0mL), the organic phase was separated, the aqueous phase was extracted with DCM, the organic phases were combined, the solvent was spun off under reduced pressure, and the crude product was isolated and purified by prep. plate (DCM/MeOH (20/1)) to afford 7y (43.0mg) as a white solid in 80% yield.
7y:1H NMR(400MHz,(CD3)2SO)δ8.04(d,J＝8.0Hz,2H),7.83(d,J＝8.4Hz,2H),7.70(d,J＝8.4Hz,2H),7.39(d,J＝8.0Hz,2H),3.88(s,3H),3.64(s,2H).13C NMR(100MHz,(CD3)2SO)δ173.06,166.56,144.95,137.60,135.91,130.67,130.30,128.81,127.34,127.31,52.66,40.76.HRMS(ESI-TOF)m/z Calcd for C16H13O4[M-H]-269.0819,found:269.0824.
Example 75
Figure BDA0002375181170000592
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8z (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc (10/1)) to give 7z (45.0mg) as a white solid in 79% yield.
7z:1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.8Hz,2H),7.65(d,J＝8.4Hz,2H),7.59(d,J＝8.4Hz,2H),7.38(d,J＝8.4Hz,2H),3.94(s,3H),3.72(s,3H),3.69(s,2H)；13C NMR(100MHz,CDCl3)δ171.86,166.99,145.17,138.87,133.98,130.10,129.86,128.90,127.46,126.94,52.15,52.12,40.81.HRMS(EI)m/z Calcd for C17H16O4(M+)284.1043,found:284.1043.
Example 76
Figure BDA0002375181170000601
To a 25mL Schlenk tube under nitrogen was added sequentially 8aa (0.2mmol) of the mono-substituted aromatic hydrocarbon substrate, thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.8mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of 1M HCl (5.0mL), the organic phase was separated, the aqueous phase was extracted with DCM, the organic phases were combined, the solvent was spun off under reduced pressure, and the crude product was isolated via prep. plate purification (DCM/MeOH (20/1)) to afford 7aa (45.0mg) as a white solid in 79% yield.
7aa:1H NMR(400MHz,(CD3)2SO)δ8.02(d,J＝8.8Hz,2H),7.80(d,J＝8.4Hz,2H),7.66(d,J＝8.4Hz,2H),7.40(d,J＝8.4Hz,2H),3.88(s,3H),3.65(dd,J＝14.0,7.0Hz,1H),1.36(d,J＝7.2Hz,3H).13C NMR(100MHz,(CD3)2SO)δ176.17,166.55,145.07,143.52,137.25,130.26,128.70,128.68,127.26,127.22,52.62,46.01,19.38.HRMS(EI)m/z Calcdfor C17H16O4(M+)284.1045,found:284.1043.
Example 77
Figure BDA0002375181170000611
To a 25mL Schlenk tube under nitrogen was added sequentially the monosubstituted aromatic substrate 8ab (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (10/1) to give 7ab (44.0mg) as a white solid in 63% yield.
7ab:1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.0Hz,2H),7.65(d,J＝8.4Hz,2H),7.59(d,J＝8.4Hz,2H),7.49(d,J＝8.4Hz,2H),3.94(s,3H),3.67(s,3H),2.55–2.48(m,2H),1.79–1.65(m,5H),1.55–1.45(m,2H),1.32–1.28(m,1H)；13C NMR(100MHz,CDCl3)δ175.56,167.00,145.06,143.91,138.31,130.08,128.85,127.28,126.88,126.54,52.11,50.80,34.68,25.53,23.64.HRMS(EI)m/z Calcd for C22H24O4(M+)352.1669,found:352.1672.
Example 78
Figure BDA0002375181170000612
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8ac (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (5/1)) to afford 7ac (54.6mg) as a white solid in 61% yield.
7ac:1H NMR(400MHz,CDCl3)δ8.04(d,J＝8.8Hz,2H),7.82–7.78(m,2H),7.72–7.67(m,2H),7.57(d,J＝8.8Hz,2H),7.47(d,J＝8.0Hz,2H),7.26(d,J＝8.0Hz,2H),5.21(dd,J＝10.8,6.0Hz,1H),3.92(s,3H),3.80(s,3H),3.69–3.58(m,2H)；13C NMR(100MHz,CDCl3)δ169.24,167.46,166.93,144.99,138.36,136.82,134.15,131.54,129.99,129.40,128.75,127.36,126.76,123.52,53.06,52.94,52.07,34.30.HRMS(EI)m/z Calcd for C26H22NO6[M+H]+444.1442,found:444.1443.
Example 79
Figure BDA0002375181170000621
To a 25mL Schlenk tube under nitrogen was added sequentially 8ad (0.2mmol) of the mono-substituted aromatic substrate, 0.24mmol of thianthrene-S-oxide, DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate isolation (hexane/EtOAc (2/1)) to give 7ad (40.0mg) as a white solid in 57% yield.
7ad:1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.4Hz,2H),7.64(d,J＝8.0Hz,2H),7.60(d,J＝8.0Hz,2H),7.31(d,J＝8.0Hz,2H),4.75–4.69(m,1H),4.28–4.19(m,2H),3.94(s,3H),3.36(dd,J＝13.2,3.2Hz,1H),2.85(dd,J＝13.6,9.6Hz,1H),2.58(s,3H).13C NMR(100MHz,CDCl3)δ170.59,167.13,153.65,144.91,139.14,135.18,130.17,130.01,128.98,127.83,126.94,66.18,54.96,52.24,37.50,23.82.HRMS(ESI-TOF)m/z Calcd forC20H19NNaO5[M+Na]+376.1155,found:376.1161.
Example 80
Figure BDA0002375181170000631
To a 25mL Schlenk tube under nitrogen was added sequentially the monosubstituted aromatic substrate 8ae (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (10/1)) to afford 7ae (47.0mg) as a white solid in 82% yield.
7ae:1H NMR(400MHz,CDCl3)δ8.08(d,J＝8.8Hz,2H),7.61(d,J＝8.8Hz,2H),7.57(d,J＝8.8Hz,2H),7.01(d,J＝8.8Hz,2H),4.29(dd,J＝10.8,3.2Hz,1H),4.01(dd,J＝10.8,5.6Hz,1H),3.93(s,1H),3.41–3.36(m,1H),2.93(t,J＝4.4Hz,1H),2.79(dd,J＝4.8,2.8Hz,1H)；13C NMR(100MHz,CDCl3)δ167.03,158.70,145.05,132.97,130.10,128.40,128.34,126.49,115.06,68.84,52.07,50.10,44.69.HRMS(ESI-TOF)m/z Calcd forC17H17O4[M+H]+285.1121,found:285.1126.
Example 81
Figure BDA0002375181170000632
To a 25mL Schlenk tube under nitrogen was added sequentially 8af (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane (2/1)) to give 7af (40.0mg) as a white solid in 62% yield.
7af:1H NMR(400MHz,CDCl3)δ8.13(d,J＝8.4Hz,2H),7.73–7.68(m,4H),7.66(d,J＝8.0Hz,2H),7.57(d,J＝8.4Hz,2H),7.43(d,J＝8.4Hz,2H),3.95(s,3H)；13C NMR(100MHz,CDCl3)δ166.95,144.89,139.73,139.17,138.85,133.68,130.17,129.02,128.27,127.74,127.46,126.89,52.15.HRMS(EI)m/z Calcd for C20H15ClO2(M+)322.0755,found:322.0756.
Example 82
Figure BDA0002375181170000641
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8ag (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane/DCM (1/1)) to give 7ag (108.0mg) as a white solid in 97% yield.
7ag:1H NMR(400MHz,CDCl3)δ8.30(d,J＝8.8Hz,2H),8.07(d,J＝8.4Hz,2H),7.89(d,J＝8.8Hz,2H),7.58(d,J＝8.4Hz,2H),7.51(d,J＝8.4Hz,2H),7.29–7.26(m,2H),7.25–7.21(m,2H),7.19–7.13(m,3H),3.92(s,3H),3.34–3.28(m,2H),3.23–3.18(m,2H),2.62–2.51(m,4H)；13C NMR(100MHz,CDCl3)δ166.88,150.02,145.94,145.04,144.60,143.12,137.84,130.11,128.97,128.82,128.51,127.46,127.29,126.78,126.73,126.51,124.32,52.13,44.17,43.16,35.53.HRMS(ESI-TOF)m/z Calcd for C31H28O6N2SNa[M+Na]+579.1560,found:579.1565.
Example 83
Figure BDA0002375181170000651
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8ah (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (10/1)) to afford 7ah (70.0mg) as a white solid in 91% yield.
7ah:1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.8Hz,2H),7.63(d,J＝8.4Hz,2H),7.60(d,J＝8.8Hz,2H),7.46(d,J＝9.2Hz,2H),7.08(d,J＝8.8Hz,2H),6.94(d,J＝9.2Hz,2H),3.95(s,3H)；13C NMR(100MHz,CDCl3)δ157.12,156.12,144.80,135.36,132.81,130.18,128.76,128.67,126.75,120.76,119.16,116.09,52.20.HRMS(ESI-TOF)m/z Calcd forC20H15BrNaO3[M+Na]+405.0097,found:405.0102.
Example 85
Figure BDA0002375181170000652
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8ai (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified on a prep. plate (hexane/EtOAc (20/1) to give 7ai (64.0mg) as a white solid in 70% yield.
7ai:1H NMR(400MHz,CDCl3)δ8.15(dd,J＝5.2,1.2Hz,1H),8.08(d,J＝8.4Hz,2H),7.62(d,J＝8.4Hz,2H),7.59–7.53(m,3H),7.03–6.98(m,4H),6.97–6.93(m,2H),6.89–6.84(m,1H),6.75(d,J＝8.4Hz,1H),5.63–5.56(m,1H),4.23–4.18(m,1H),4.11–4.06(m,1H),3.93(s,3H),1.49(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3)δ167.02,163.13,158.90,155.49,149.81,146.76,144.99,138.70,134.07,130.11,128.49,126.62,121.00,117.75,116.77,115.87,111.67,109.97,71.05,69.23,52.09,16.99.HRMS(ESI-TOF)m/z Calcdfor C28H26NO5[M+H]+456.1805,found:456.1818.
Example 85
Figure BDA0002375181170000661
To a 25mL Schlenk tube under nitrogen was added sequentially the mono-substituted aromatic substrate 8aj (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the flask was closed and reacted at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by prep. plate separation (DCM) to give 7aj (87.0mg) as a white solid in 99% yield.
7aj:1H NMR(400MHz,CDCl3)δ8.14(d,J＝8.4Hz,2H),8.04(dd,J＝8.8,2.4Hz,1H),7.80(d,J＝9.2Hz,1H),7.74(d,J＝2.4Hz,1H),7.70(d,J＝8.8Hz,2H),7.67(d,J＝8.4Hz,2H),7.41(s,1H),7.17(d,J＝8.4Hz,2H),3.96(s,3H),3.20(s,3H)；13C NMR(100MHz,CDCl3)δ166.84,154.23,146.01,144.10,143.69,137.84,134.06,130.25,129.52,129.28,126.98,120.05,119.67,117.37,112.10,52.20,40.65.HRMS(ESI-TOF)m/z Calcd forC21H17O7N2S[M-H]-441.0762,found:441.0768.
Example 86
Figure BDA0002375181170000671
To a 25mL Schlenk tube under nitrogen was added sequentially 8ak (0.2mmol) of the mono-substituted aromatic substrate, thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.8mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under nitrogen, DMF (1.0mL) was added, the flask was screwed on, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of 1M HCl (5.0mL), the organic phase was separated, the aqueous phase was extracted with DCM, the organic phases were combined, the solvent was spun off under reduced pressure, and the crude product was isolated and purified via prep-plate (hexane/EtOAc (2/1) to afford 7ak (57.0mg) as a white solid in 76% yield.
7ak:1H NMR(400MHz,(CD3)2SO)δ12.51(s,1H),8.07(d,J＝8.4Hz,2H),7.90(d,J＝8.4Hz,2H),7.87(d,J＝8.0Hz,2H),7.69(d,J＝7.6Hz,2H),7.57(t,J＝8.2Hz,1H),7.30–7.23(m,1H),3.89(s,3H),3.80(q,J＝7.0Hz,1H),1.42(d,J＝7.2Hz,3H).13C NMR(100MHz,(CD3)2SO)δ175.33,166.51,160.68,158.23,144.52,143.90(d,J＝8.0Hz),138.59,135.38,131.06(d,J＝4.0Hz),130.33,129.87(d,J＝3.0Hz),129.07,127.56(d,J＝27.0Hz),126.40(d,J＝13.0Hz),124.62(d,J＝3.0Hz),115.75(d,J＝23.0Hz),52.66,44.60,18.75.19F NMR(375MHz,(CD3)2SO)δ-117.89.HRMS(ESI-TOF)m/z Calcd for C23H20FO4[M+H]+379.1340,found:379.1339.
Example 87
Figure BDA0002375181170000672
To a 25mL Schlenk tube under nitrogen was added sequentially 8aa (0.2mmol) of the mono-substituted aromatic hydrocarbon substrate, thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (1.0mmol), an alkenylborate substrate 6f (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was carried out at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of 0.25M HCl (5.0mL), the organic phase was separated, the water box was extracted with DCM, the organic phases were combined, the solvent was spun off under reduced pressure, and the crude product was isolated and purified by prep. plate (DCM/MeOH (25/1)) to afford drug molecule 8(Tetriprofen) (24.0mg) in 52% yield.
Tetriprofen:1H NMR(400MHz,CDCl3)δ7.34(d,J＝8.4Hz,2H),7.26–7.23(m,2H),6.12–6.07(m,1H),3.72(q,J＝7.2Hz,1H),2.41–2.35(m,2H),2.23–2.17(m,2H),1.80–1.74(m,2H),1.69–1.62(m,2H),1.50(d,J＝7.2Hz,3H).
Example 88
Figure BDA0002375181170000681
To a 25mL Schlenk tube under nitrogen was added sequentially 8aa (0.2mmol) of the mono-substituted aromatic hydrocarbon substrate, thianthrene-S-oxide (0.24mmol), DCM (0.2mL) and stirred at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (1.0mmol), an alkenylboronic acid ester substrate 6d (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was carried out at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of 0.25M HCl (5.0mL), the organic phase was separated, the water box was extracted with DCM, the organic phases were combined, the solvent was spun off under reduced pressure, and the crude product was isolated and purified by prep. plate (DCM/MeOH (25/1)) to give 9(29.0mg) in 71% yield. 9(0.2mmol) was dissolved in 5mL of ethanol, palladium on carbon (4.2mg,10 wt%) was added, and then hydrogen was replaced 5 times. Followed by a reaction at 50 ℃ for 4 hours. After the reaction, the mixture was filtered through celite and rinsed with ethyl acetate. The organic phases were combined, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (DCM/MeOH (20/1)) to give the drug molecule 10(Ibuprofen) (36.0mg) in 86% yield.
9:1H NMR(400MHz,CDCl3)δ7.28–7.25(m,2H),7.18(d,J＝8.4Hz,2H),6.23(s,1H),3.72(q,J＝7.2Hz,1H),1.89(s,3H),1.85(s,3H),1.51(d,J＝7.2Hz,3H).
Ibuprofen:1H NMR(400MHz,CDCl3)δ7.22(d,J＝8.0Hz,2H),7.10(d,J＝8.0Hz,2H),3.70(q,J＝7.2Hz,1H),2.44(d,J＝7.2Hz,2H),1.89–1.79(m,1H),1.49(d,J＝7.2Hz,3H),0.89(d,J＝6.8Hz,6H).
Example 89
Figure BDA0002375181170000691
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 8e (6.0mmol), thianthrene-S-oxide (7.2mmol) and DCM (30.0mL) in that order, followed by stirring at-40 ℃. Tf2O (7.2mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), pinacol phenylboronate (9.0mmol) and palladium bis (tri-tert-butylphosphino) (0.3mmol) were added under a nitrogen atmosphere, DMF (30.0mL) was added, the flask was closed, and the reaction was carried out at 50 ℃ for 12 hours. After the reaction was complete, the solvent was filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate isolation (toluene/hexane (40/1)) to give 11 as a white solid (1.24g) in 84% yield. Under a nitrogen atmosphere, 11(0.2mmol), NBS (0.2mmol), AIBN (0.02mmol), and CCl were charged into a 20mL reaction flask4(2.5 mL). The reaction was refluxed for 50 minutes. Cooled to room temperature, the reaction mixture was filtered and washed 2 times with n-hexane (2X 2 mL). After concentration, imidazole (1.57mmol), potassium carbonate (0.61mmol) and acetonitrile (4.3mL) were added. The reaction was refluxed for 1 hour. After cooling to room temperature, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (5/3)) to afford the drug molecule 12(Bifonazole) (47.9mg) in 77% yield.
11:1H NMR(400MHz,CDCl3)δ7.59–7.54(m,2H),7.54–7.50(m,2H),7.45–7.39(m,2H),7.35–7.19(m,8H),4.03(s,2H).
Bifonazole:1H NMR(400MHz,CDCl3)δ7.58(d,J＝8.1Hz,4H),7.49–7.42(m,3H),7.41–7.33(m,4H),7.22–7.10(m,5H),6.90(s,1H),6.57(s,1H).
Example 90
Figure BDA0002375181170000692
To a 25mL Schlenk tube, substrate 14(0.2mmol), phenoxathiin-10-oxide or thianthrene-S-oxide (0.6mmol) was added in this order under a nitrogen atmosphere, DCM (0.3mL) was added, and the mixture was stirred at-40 ℃. Tf2O (0.6mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), phenylboronic acid (0.6mmol) and bis (tri-tert-butylphosphino) palladium (0.02mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the cap was screwed on, and the reaction was carried out at 50 ℃ for 12 hours. After the reaction was completed, 0.2M (10.0mL) hydrochloric acid was added to quench the reaction, and the organic phase was separated. The aqueous phase was extracted 3 times with DCM (3X 10 mL). The organic phases were combined, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (PhMe/isoproapanol/AcOH ═ 100:10:1) to give drug molecule 15(57mg, 73%) and monosubstituted product 15' (8.0mg, 13%).
15:1H NMR(400MHz,CDCl3)δ7.59–7.27(m,16H),6.95(d,J＝8.8Hz,2H),4.96–4.91(m,1H),3.40–3.33(m,2H).13C NMR(100MHz,CDCl3)δ175.34,156.88,140.75,140.45,140.04,135.32,135.01,129.92,128.74,128.73,128.36,127.24,127.03,126.90,126.80,115.65,77.42,38.42.HRMS(ESI-TOF)m/z Calcd for C27H21O3[M-H]-393.1496,found:393.1504.
15’:1H NMR(400MHz,CDCl3)δ7.53–7.25(m,13H),6.91(d,J＝8.8Hz,2H),4.89(t,J＝6.4Hz,1H),3.35–3.26(m,2H).
Example 91
Figure BDA0002375181170000701
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. TFAA (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.005mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours by screwing the cap. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3k (39.0mg) as a white solid in 86% yield.
Example 92
Figure BDA0002375181170000711
Under nitrogen atmosphere, a 25mL Schlenk tube was charged with mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol), and HBF in that order4·OEt2(0.24mmol), CH was added3CN (1.0mL), followed by stirring at-40 ℃. TFAA (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid substrate 4k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.005mmol) and acetone (1.0mL) were added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours by screwing the cap. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3k (40.7mg) as a white solid in 90% yield.
Example 93
Figure BDA0002375181170000712
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Tf2O (0.24mmol) was slowly added dropwise thereto, followed by stirring at-40 ℃ for 30 minutes and then at room temperature for 1 hour. Subsequently, sodium bicarbonate (0.6mmol), alkenyl borate substrate 6k (0.3mmol), bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane) to give 5k (25.5mg) as a colorless liquid in 63% yield.
5k:1H NMR(400MHz,CDCl3)δ＝7.26(d,J＝7.9Hz,2H),7.12(d,J＝7.9Hz,2H),6.37(d,J＝15.8Hz,1H),6.19(dt,J＝15.8,6.9Hz,1H),2.34(s,3H),2.20(dd,J＝16.0,8.0Hz,2H),1.47(q,J＝7.4Hz,2H),1.41-1.27(m,7H),0.92(m,3H).
Example 94
Figure BDA0002375181170000721
To a 25mL Schlenk tube under nitrogen was added the mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), 6l (0.3mmol) of an alkenylboronic acid ester substrate, and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 5l (37.4mg) of a white solid in 82% yield.
5l：1H NMR(400MHz,CDCl3):δ7.44–7.40(m,4H),7.33(d,J＝8.4Hz,2H),7.19(d,J＝8.0Hz,2H),7.06(d,J＝16.0Hz,1H),7.00(d,J＝16.0Hz,1H),2.37(s,3H).
Example 95
Figure BDA0002375181170000722
To a 25mL Schlenk tube under nitrogen was added in sequence mono-substituted aromatic substrate 1a (0.2mmol), thianthrene-S-oxide (0.24mmol), DCM (1.0mL) followed by-40 deg.CStirring the mixture. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), alkenyl borate substrate 6m (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, DMF (1.0mL) was added, the flask was closed, and the reaction was stirred at 50 ℃ for 12 hours. After the reaction was complete, the reaction was quenched by addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was isolated and purified by preparative plate (hexane) to give 5m (21.0mg) as a yellow solid in 52% yield.
5m：1H NMR(400MHz,CDCl3):1H NMR(400MHz,CDCl3)δ(ppm)7.35(d,J＝8.0Hz,2H),7.19–7.09(m,4H),7.03(d,J＝3.2Hz,1H),6.99–6.96(m,1H),6.89(d,J＝16.0Hz,1H),2.33(s,3H)。
Example 96
Figure BDA0002375181170000731
To a 25mL Schlenk tube under a nitrogen atmosphere were added the monosubstituted arene substrate 1a (0.2mmol), phenoxathiin-10-oxide (0.24mmol) and DCM (1.0mL) in that order, followed by stirring at-40 ℃. Slowly drop Tf2After O (0.24mmol), the mixture was stirred at-40 ℃ for 30 minutes, followed by stirring at room temperature for 1 hour. Subsequently, sodium hydrogencarbonate (0.6mmol), arylboronic acid ester substrate 4k (0.3mmol), and bis (tri-tert-butylphosphino) palladium (0.01mmol) were added under a nitrogen atmosphere, acetone (1.0mL) was added, the cap was screwed on, and the reaction was stirred at room temperature for 12 hours. After the reaction was complete, the reaction was quenched by the addition of a small amount of DCM, filtered through celite, the solvent was spun off under reduced pressure and the crude product was purified by preparative plate separation (hexane/EtOAc (20/1)) to give 3k (43.0mg) as a white solid in 95% yield.
3k：1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,2H),7.65(d,J＝7.2Hz,2H),7.53(d,J＝7.6Hz,2H),7.30–7.26(m,2H),3.94(s,3H),2.41(s,3H)。

Claims (10)

1.一种如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，包括以下步骤：1. a preparation method of a para-substituted aryl compound as shown in formula (I), is characterized in that, comprises the following steps: 惰性气氛下，溶剂中，在碱和钯催化剂的作用下，如式(II)所示的芳基锍盐与如式(III)所示的硼化物进行偶联反应，即可；In an inert atmosphere, in a solvent, under the action of a base and a palladium catalyst, the aryl sulfonium salt shown in the formula (II) and the boride shown in the formula (III) are subjected to a coupling reaction, that is, a coupling reaction;
Figure FDA0002375181160000011
Figure FDA0002375181160000011
 其中，in, X为O或S；X is O or S; Y为OTf、TFA或BF4；Y is OTf, TFA or BF 4 ; R为氨基、羟基、卤素、“含1个或2个杂原子，杂原子为O、S和N中的一种或多种的3-7元杂环烷基”、4-6元环烷基、-COOR4、-OR5、C1-C10烷基、RA取代的C1-C10烷基、C1-C10烷氧基、RB取代的C1-C10烷氧基、C6-C10芳基、RC取代的C6-C10芳基、苄基、RD取代的苄基、
Figure FDA0002375181160000012
Figure FDA0002375181160000013
R is amino, hydroxy, halogen, "3-7 membered heterocycloalkyl containing 1 or 2 heteroatoms, and the heteroatoms are one or more of O, S and N", 4-6 membered cycloalkane base, -COOR 4 , -OR 5 , C1-C10 alkyl, RA substituted C1-C10 alkyl, C1-C10 alkoxy, RB substituted C1-C10 alkoxy, C6-C10 aryl, R C substituted C6-C10 aryl, benzyl, R D substituted benzyl,
Figure FDA0002375181160000012
Figure FDA0002375181160000013
 R4为H或C1-C3烷基；R 4 is H or C1-C3 alkyl; R5为C6-C10芳基、R5A取代的C6-C10芳基或乙酰基；R5A为卤素、氨基、硝基、C1-C3烷基、C1-C3烷氧基、-NHMs或
Figure FDA0002375181160000014
R 5 is C6-C10 aryl, R 5A substituted C6-C10 aryl or acetyl; R 5A is halogen, amino, nitro, C1-C3 alkyl, C1-C3 alkoxy, -NHMs or
Figure FDA0002375181160000014
 RA为卤素、乙酰氧基(OAc)、C1-C3烷氧基、-NPhth、-COOR6或“含1个或2个杂原子，杂原子为O、S和N中的一种或多种的3-7元杂环烷基”；R6为H或C1-C3烷基；R A is halogen, acetoxy (OAc), C1-C3 alkoxy, -NPhth, -COOR 6 or "containing 1 or 2 heteroatoms, and the heteroatoms are one or more of O, S and N. 3-7 membered heterocycloalkyl "; R 6 is H or C1-C3 alkyl; RB为卤素、羧基、C6-C10芳基或“含1个或2个杂原子，杂原子为O、S和N中的一种或多种的3-7元杂环烷基”；R B is halogen, carboxyl, C6-C10 aryl or "3-7 membered heterocycloalkyl containing 1 or 2 heteroatoms, and the heteroatoms are one or more of O, S and N"; RC和RD独立地为卤素、羧基取代的C1-C3烷基、C1-C3烷基或C1-C3烷氧基；R C and R D are independently halogen, carboxy-substituted C1-C3 alkyl, C1-C3 alkyl or C1-C3 alkoxy; R1和R2独立地为H或C1-C10烷基，或者OR1和OR2与它们共同连接的硼原子一起形成5～6元杂环烷基或C1-C3烷基取代的5～6元杂环烷基；R 1 and R 2 are independently H or C1-C10 alkyl, or OR 1 and OR 2 together with the boron atom to which they are commonly attached form a 5-6 membered heterocycloalkyl or C1-C3 alkyl substituted 5-6 membered heterocycloalkyl; R3为C6-C10芳基、RF取代的C6-C10芳基、“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”、RG取代的“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”或
Figure FDA0002375181160000021
R 3 is a C6-C10 aryl group, a C6-C10 aryl group substituted by R F , a 5-12-membered heteroaryl group containing 1 to 4 heteroatoms, and the heteroatoms are one or more of O, S and N group", R G -substituted "5-12-membered heteroaryl group containing 1 to 4 heteroatoms, the heteroatoms being one or more of O, S and N" or
Figure FDA0002375181160000021
 RF和RG独立地为卤素、氨基、硝基、羟基、TMS、乙酰基、-SR10、-COOR11、C1-C6烷基、卤素取代的C1-C6烷基、C1-C6烷氧基、卤素取代的C1-C6烷氧基或C6-C10芳基；R10为C1-C3烷基；R11为H或C1-C3烷基；R F and R G are independently halogen, amino, nitro, hydroxy, TMS, acetyl, -SR 10 , -COOR 11 , C1-C6 alkyl, halogen substituted C1-C6 alkyl, C1-C6 alkoxy base, halogen-substituted C1-C6 alkoxy or C6-C10 aryl; R 10 is C1-C3 alkyl; R 11 is H or C1-C3 alkyl; R7、R8和R9的定义为以下(i)～(iii)任一项：R 7 , R 8 and R 9 are defined as any of the following (i) to (iii): (i)R7、R8和R9独立地为H、C1-C10烷基、卤素取代的C1-C10烷基、C1-C10烷氧基、C6-C10芳基、RE取代的C6-C10芳基、“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”或-COOR12，R12为C1-C3烷基；RE为卤素、乙酰氧基(OAc)、C1-C3烷基、卤素取代的C1-C3烷基、C1-C3烷氧基、卤素取代的C1-C3烷氧基、-NPhth或-COOR13，R13为C1-C3烷基；(i) R 7 , R 8 and R 9 are independently H, C1-C10 alkyl, halogen-substituted C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, R E substituted C6- C10 aryl, "5-12-membered heteroaryl containing 1 to 4 heteroatoms, and the heteroatoms are one or more of O, S and N" or -COOR 12 , R 12 is C1-C3 alkyl ; R E is halogen, acetoxy (OAc), C1-C3 alkyl, halogen-substituted C1-C3 alkyl, C1-C3 alkoxy, halogen-substituted C1-C3 alkoxy, -NPhth or -COOR 13 , R 13 is C1-C3 alkyl; (ii)R7为H，R8和R9与它们共同连接的碳原子一起形成4-6元环烷基；(ii) R7 is H, and R8 and R9 together with the carbon atoms to which they are commonly attached form a 4-6 membered cycloalkyl; (iii)R7、R8以及与其相连的碳碳双键形成“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5～7元杂环烯基”、R7A取代的“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5～7元杂环烯基”、5～7元环烯基或
Figure FDA0002375181160000022
R9为H；R7A为C1-C3烷基或叔丁氧羰基。(iii) R 7 , R 8 and the carbon-carbon double bond attached to them form "a 5- to 7-membered heterocycloalkenyl group containing 1 to 2 heteroatoms, the heteroatoms being one or more of O, S and N. ", R 7A substituted "5-7-membered heterocycloalkenyl containing 1-2 heteroatoms, the heteroatoms being one or more of O, S and N", 5-7-membered cycloalkenyl or
Figure FDA0002375181160000022
R 9 is H; R 7A is C1-C3 alkyl or tert-butoxycarbonyl. 2.如权利要求1所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，所述钯催化剂为Pd(tBu3P)2、Pd(PPh3)4、PdCl2(PPh3)2、PdCl2(dppf)、PdCl2(MeCN)2、Pd(OAc)2和Pd2(dba)3中的一种或多种；较佳地，当所述钯催化剂为Pd(OAc)2或Pd2(dba)3时，反应体系中还加入配体，所述配体为PPh3、BrettPhos、P(Cy)3、P(tBu)3和BrettPhos中的一种或多种；2. the preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 1, is characterized in that, described palladium catalyst is Pd( t Bu 3 P) 2 , Pd(PPh 3 ) 4. One or more of PdCl 2 (PPh 3 ) 2 , PdCl 2 (dppf), PdCl 2 (MeCN) 2 , Pd(OAc) 2 and Pd 2 (dba) 3 ; preferably, when the When the palladium catalyst is Pd(OAc) 2 or Pd 2 (dba) 3 , a ligand is also added to the reaction system, and the ligand is in PPh 3 , BrettPhos, P(Cy) 3 , P( t Bu) 3 and BrettPhos one or more of; 和/或，所述钯催化剂与所述如式(II)所示的芳基锍盐的摩尔比为1：(10-40)；And/or, the molar ratio of the palladium catalyst to the arylsulfonium salt shown in formula (II) is 1: (10-40); 和/或，所述惰性气氛为氮气或氩气；And/or, the inert atmosphere is nitrogen or argon; 和/或，所述溶剂为酰胺类溶剂、亚砜类溶剂、酮类溶剂、醇类溶剂、腈类溶剂和卤代烷烃类溶剂中的一种或多种，较佳地，所述酰胺类溶剂为N-甲基吡咯烷酮、二甲基甲酰胺和二甲基乙酰胺中的一种或多种；所述亚砜类溶剂为二甲基亚砜；所述酮类溶剂可为丙酮；所述醇类溶剂为甲醇、乙醇和2-甲基-2-丁醇中的一种或多种；所述腈类溶剂为乙腈；所述卤代烷烃类溶剂为二氯甲烷和/或二氯乙烷；And/or, the solvent is one or more of amide-based solvents, sulfoxide-based solvents, ketone-based solvents, alcohol-based solvents, nitrile-based solvents and halogenated alkane-based solvents, preferably, the amide-based solvents is one or more of N-methylpyrrolidone, dimethylformamide and dimethylacetamide; the sulfoxide solvent is dimethyl sulfoxide; the ketone solvent can be acetone; the The alcohol solvent is one or more of methanol, ethanol and 2-methyl-2-butanol; the nitrile solvent is acetonitrile; the halogenated alkane solvent is dichloromethane and/or dichloroethane ; 和/或，所述如式(II)所示的芳基锍盐与所述溶剂的摩尔体积比为0.01-5.0mol/L；And/or, the molar volume ratio of the arylsulfonium salt shown in formula (II) to the solvent is 0.01-5.0mol/L; 和/或，所述碱为碱金属醋酸盐、碱金属碳酸盐、碱金属碳酸氢盐、碱金属羧酸盐、碱金属醇盐、碱金属氟化物和碱金属磷酸盐中的一种或多种；较佳地，所述碱金属醋酸盐为醋酸钾、醋酸钠、醋酸铯和醋酸锂中的一种或多种；所述碱金属碳酸盐为碳酸钾、碳酸钠、碳酸锂和碳酸铯中的一种或多种；所述碱金属碳酸氢盐为碳酸氢钾、碳酸氢钠和碳酸氢铯中的一种或多种；所述碱金属羧酸盐为甲酸钾、甲酸钠、特戊酸钾、特戊酸钠和特戊酸铯中的一种或多种；所述碱金属醇盐为甲醇钠、甲醇钾、乙醇钠和乙醇钾中的一种或多种；所述碱金属氟化物为氟化钠、氟化钾和氟化铯中的一种或多种；所述碱金属磷酸盐为磷酸二氢钾和/或磷酸钾；And/or, the alkali is a kind of in alkali metal acetate, alkali metal carbonate, alkali metal bicarbonate, alkali metal carboxylate, alkali metal alkoxide, alkali metal fluoride and alkali metal phosphate or more; preferably, the alkali metal acetate is one or more of potassium acetate, sodium acetate, cesium acetate and lithium acetate; the alkali metal carbonate is potassium carbonate, sodium carbonate, carbonic acid One or more in lithium and cesium carbonate; Described alkali metal bicarbonate is one or more in potassium bicarbonate, sodium bicarbonate and cesium bicarbonate; Described alkali metal carboxylate is potassium formate, One or more of sodium formate, potassium pivalate, sodium pivalate and cesium pivalate; Described alkali metal alkoxide is one or more of sodium methoxide, potassium methoxide, sodium ethoxide and potassium ethoxide; The alkali metal fluoride is one or more of sodium fluoride, potassium fluoride and cesium fluoride; the alkali metal phosphate is potassium dihydrogen phosphate and/or potassium phosphate; 和/或，所述如式(II)所示的芳基锍盐与所述碱的摩尔比为1：(1-6)；And/or, the molar ratio of the arylsulfonium salt shown in formula (II) to the base is 1:(1-6); 和/或，所述如式(II)所示的芳基锍盐与所述如式(III)所示的硼化物的摩尔比为1：(1-3)；And/or, the molar ratio of the aryl sulfonium salt represented by the formula (II) to the boride represented by the formula (III) is 1: (1-3); 和/或，所述偶联反应的温度为25℃-150℃；And/or, the temperature of the coupling reaction is 25°C-150°C; 和/或，所述偶联反应的时间可为1-48小时；And/or, the time of described coupling reaction can be 1-48 hours; 和/或，所述如式(I)所示的对位取代芳基化合物的制备方法还包括以下后处理步骤：猝灭反应后过滤，去除溶剂后进行色谱分离，即可。And/or, the preparation method of the para-substituted aryl compound represented by the formula (I) further includes the following post-processing steps: filtering after quenching reaction, and performing chromatographic separation after removing solvent. 3.如权利要求1所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，所述钯催化剂为Pd(tBu3P)2、Pd(PPh3)4、Pd(OAc)2、和Pd2(dba)3中的一种或多种；较佳地，当所述钯催化剂为Pd(OAc)2或Pd2(dba)3时，反应体系中还加入配体，所述配体为PPh3、BrettPhos和P(Cy)3中的一种或多种；3. the preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 1, is characterized in that, described palladium catalyst is Pd( t Bu 3 P) 2 , Pd(PPh 3 ) 4. One or more of Pd(OAc) 2 and Pd 2 (dba) 3 ; preferably, when the palladium catalyst is Pd(OAc) 2 or Pd 2 (dba) 3 , in the reaction system Also adding a ligand, the ligand is one or more of PPh 3 , BrettPhos and P(Cy) 3 ; 和/或，所述溶剂为酰胺类溶剂、酮类溶剂、醇类溶剂和卤代烷烃类溶剂中的一种或多种；And/or, the solvent is one or more of amide solvents, ketone solvents, alcohol solvents and halogenated alkane solvents; 和/或，所述碱为碱金属醋酸盐、碱金属碳酸盐、碱金属碳酸氢盐和碱金属磷酸盐中的一种或多种；较佳地所述碱为碳酸氢钠；And/or, the alkali is one or more of alkali metal acetate, alkali metal carbonate, alkali metal bicarbonate and alkali metal phosphate; preferably, the alkali is sodium bicarbonate; 和/或，所述偶联反应的温度为25-35℃。And/or, the temperature of the coupling reaction is 25-35°C. 4.如权利要求1所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，R中，所述卤素为F、Cl、Br或I，例如F或Cl；4. the preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 1, is characterized in that, in R, described halogen is F, Cl, Br or I, for example F or Cl ; 和/或，R中，所述“含1个或2个杂原子，杂原子为O、S和N中的一种或多种的3-7元杂环烷基”为“含1个或2个杂原子，杂原子为O和/或N的3-6元杂环烷基”，例如环氧乙烷基、四氢呋喃基、四氢吡喃基或吗啉基；And/or, in R, the "3-7 membered heterocycloalkyl containing 1 or 2 heteroatoms, and the heteroatoms are one or more of O, S and N" is "containing 1 or 2 heteroatoms, the heteroatoms are O and/or N 3-6 membered heterocycloalkyl", such as oxiranyl, tetrahydrofuranyl, tetrahydropyranyl or morpholinyl; 和/或，R中，所述4-6元环烷基为5-6元环烷基，例如环戊烷基或环己烷基；And/or, in R, the 4-6 membered cycloalkyl group is a 5-6 membered cycloalkyl group, such as cyclopentyl or cyclohexyl; 和/或，R4中，所述C1-C3烷基为甲基、乙基、正丙基或异丙基；And/or, in R 4 , the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl; 和/或，R5中，所述C6-C10芳基和所述R5A取代的C6-C10芳基中的C6-C10芳基独立地为苯基或萘基；And/or, in R 5 , the C6-C10 aryl group in the C6-C10 aryl group and the C6-C10 aryl group substituted by the R 5A are independently phenyl or naphthyl; 和/或，R5A中，所述卤素为F、Cl、Br或I；And/or, in R 5A , the halogen is F, Cl, Br or I; 和/或，R5A中，所述C1-C3烷基为甲基、乙基、正丙基或异丙基；And/or, in R 5A , the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl; 和/或，R5A中，所述C1-C3烷氧基为甲氧基、乙氧基、正丙氧基或异丙氧基；And/or, in R 5A , the C1-C3 alkoxy group is methoxy, ethoxy, n-propoxy or isopropoxy; 和/或，所述R5A取代的C6-C10芳基中所述R5A的取代个数为1～3个，各R5A相同或不同；And/or, the number of substitutions of the R 5A in the C6-C10 aryl group substituted by the R 5A is 1 to 3, and each R 5A is the same or different; 和/或，R中，所述C1-C10烷基和所述RA取代的C1-C10烷基中的C1-C10烷基独立地为C1-C6烷基，例如C1-C3烷基，再例如甲基、乙基、正丙基或异丙基；And/or, in R, the C1-C10 alkyl group in the C1-C10 alkyl group and the C1-C10 alkyl group substituted by R A is independently a C1-C6 alkyl group, such as a C1-C3 alkyl group, and then For example methyl, ethyl, n-propyl or isopropyl; 和/或，RA中，所述卤素为F、Cl、Br或I；And/or, in R A , the halogen is F, Cl, Br or I; 和/或，RA中，所述C1-C3烷氧基为甲氧基、乙氧基、正丙氧基或异丙氧基；And/or, in R A , the C1-C3 alkoxy group is methoxy, ethoxy, n-propoxy or isopropoxy; 和/或，R6中，所述C1-C3烷基为甲基、乙基、正丙基或异丙基；And/or, in R 6 , the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl; 和/或，RA中，所述“含1个或2个杂原子，杂原子为O、S和N中的一种或多种的3-7元杂环烷基”为“含1个或2个杂原子，杂原子为O和/或N的3-6元杂环烷基”，例如环氧乙烷基、四氢呋喃基、四氢吡喃基或吗啉基；And/or, in R A , the "3-7 membered heterocycloalkyl group containing 1 or 2 heteroatoms, and the heteroatoms are one or more of O, S and N" is "containing 1 Or 2 heteroatoms, the heteroatoms are O and/or N 3-6 membered heterocycloalkyl", such as oxiranyl, tetrahydrofuranyl, tetrahydropyranyl or morpholinyl; 和/或，R中，所述C1-C10烷氧基和所述RB取代的C1-C10烷氧基中的C1-C10烷氧基独立地为C1-C6烷氧基，例如C1-C3烷氧基，再例如甲氧基、乙氧基、正丙氧基或异丙氧基；And/or, in R, the C1-C10 alkoxy in the C1-C10 alkoxy group and the C1-C10 alkoxy group substituted by R B is independently a C1-C6 alkoxy group, such as C1-C3 Alkoxy, such as methoxy, ethoxy, n-propoxy or isopropoxy; 和/或，RB中，所述卤素为F、Cl、Br或I；And/or, in R B , the halogen is F, Cl, Br or I; 和/或，RB中，所述C6-C10芳基为苯基或萘基，例如苯基；And/or, in R B , the C6-C10 aryl group is phenyl or naphthyl, such as phenyl; 和/或，RB中，所述“含1个或2个杂原子，杂原子为O、S和N中的一种或多种的3-7元杂环烷基”为“含1个或2个杂原子，杂原子为O和/或N的3-6元杂环烷基”，例如环氧乙烷基、四氢呋喃基、四氢吡喃基或吗啉基；And/or, in R B , the "3-7 membered heterocycloalkyl containing 1 or 2 heteroatoms, and the heteroatoms are one or more of O, S and N" is "containing 1 Or 2 heteroatoms, the heteroatoms are O and/or N 3-6 membered heterocycloalkyl", such as oxiranyl, tetrahydrofuranyl, tetrahydropyranyl or morpholinyl; 和/或，R中，所述C6-C10芳基和所述RC取代的C6-C10芳基中的C6-C10芳基独立地为苯基或萘基；And/or, in R, the C6-C10 aryl group in the C6-C10 aryl group and the C6-C10 aryl group substituted by the R C is independently phenyl or naphthyl; 和/或，R中，所述RC取代的C6-C10芳基中所述RC的取代个数为1～3个，各RC相同或不同；And/or, in R , the number of RC substitutions in the C6 -C10 aryl group substituted by RC is 1 to 3, and each RC is the same or different; 和/或，R中，所述RD取代的苄基中所述RD的取代个数可为1～3个，各RD相同或不同；And/or, in R, the number of R D substitutions in the benzyl group substituted by R D may be 1 to 3, and each R D is the same or different; 和/或，RC或RD中，所述卤素为F、Cl、Br或I；And/or, in R C or R D , the halogen is F, Cl, Br or I; 和/或，RC或RD中，所述羧基取代的C1-C3烷基和所述C1-C3烷基中的C1-C3烷基独立地为甲基、乙基、正丙基或异丙基；And/or, in R C or R D , the C1-C3 alkyl group substituted by the carboxyl group and the C1-C3 alkyl group in the C1-C3 alkyl group are independently methyl, ethyl, n-propyl or isopropyl propyl; 和/或，RC或RD中，所述羧基取代的C1-C3烷基中羧基的取代个数为1～2个；And/or, in R C or R D , the number of carboxyl group substitutions in the C1-C3 alkyl group substituted by the carboxyl group is 1 to 2; 和/或，RC或RD中，所述C1-C3烷氧基为甲氧基、乙氧基、正丙氧基或异丙氧基；And/or, in R C or R D , the C1-C3 alkoxy is methoxy, ethoxy, n-propoxy or isopropoxy; 和/或，R1或R2中，所述C1-C10烷基为C1-C6烷基，例如C1-C3烷基，再例如甲基、乙基、正丙基或异丙基；And/or, in R 1 or R 2 , the C1-C10 alkyl group is a C1-C6 alkyl group, such as a C1-C3 alkyl group, and another example is methyl, ethyl, n-propyl or isopropyl; 和/或，当OR1和OR2与它们共同连接的硼原子一起形成5～6元杂环烷基或C1-C3烷基取代的5～6元杂环烷基时，所述5～6元杂环烷基和所述5～6元杂环烷基中的5～6元杂环烷基为
Figure FDA0002375181160000051
And/or, when OR 1 and OR 2 together with the boron atom to which they are connected together form a 5-6 membered heterocycloalkyl or a C1-C3 alkyl substituted 5-6 membered heterocycloalkyl, the 5-6 membered heterocycloalkyl The membered heterocycloalkyl and the 5-6 membered heterocycloalkyl in the 5-6 membered heterocycloalkyl are:
Figure FDA0002375181160000051
 和/或，所述C1-C3烷基取代的5～6元杂环烷基中C1-C3烷基的取代个数为2～6个；And/or, the number of C1-C3 alkyl substitutions in the C1-C3 alkyl-substituted 5- to 6-membered heterocycloalkyl group is 2-6; 和/或，所述C1-C3烷基取代的5～6元杂环烷基中的C1-C3烷基为甲基、乙基、正丙基或异丙基，例如甲基；And/or, the C1-C3 alkyl group in the 5-6 membered heterocycloalkyl substituted by the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl, such as methyl; 和/或，R3中，所述C6-C10芳基和所述RF取代的C6-C10芳基中的C6-C10芳基为苯基或萘基；And/or, in R 3 , the C6-C10 aryl group in the C6-C10 aryl group and the C6-C10 aryl group substituted by the R F is phenyl or naphthyl; 和/或，R3中，所述RF取代的C6-C10芳基中所述RF的取代个数为1～5个，各RF相同或不同；And/or, in R 3 , the number of R F substitutions in the C6-C10 aryl group substituted by R F is 1 to 5, and each R F is the same or different; 和/或，R3中，所述“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”和所述RG取代的“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”中的“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”独立地为“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5-10元杂芳基”，例如呋喃基、吡啶基、噻吩基、苯并噻吩基、苯并呋喃基或喹啉基；And/or, in R 3 , the "5-12-membered heteroaryl group containing 1 to 4 heteroatoms, the heteroatoms being one or more of O, S and N" and the R G substituted "Containing 1-4 heteroatoms, the heteroatoms are one or more of O, S, and N. The heteroaryl group of 5-12 members""contains 1-4 heteroatoms, and the heteroatoms are O, S 5-12-membered heteroaryl group with one or more of N" is independently "containing 1-2 heteroatoms, and the heteroatom is a 5-10-membered heteroatom of one or more of O, S and N. Heteroaryl" such as furyl, pyridyl, thienyl, benzothienyl, benzofuryl or quinolyl; 和/或，R3中，所述RG取代的“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”中所述RG的取代个数为1～3个，各RG相同或不同；And/or, in R 3 , the R G substituted "5-12-membered heteroaryl group containing 1-4 heteroatoms, and the heteroatom is one or more of O, S and N" described in The number of substitutions of R G is 1 to 3, and each R G is the same or different; 和/或，RF或RG中，所述卤素、所述卤素取代的C1-C6烷基和所述卤素取代的C1-C6烷氧基中的卤素独立地为F、Cl、Br或I；And/or, in R F or R G , the halogen in the halogen, the halogen-substituted C1-C6 alkyl group and the halogen-substituted C1-C6 alkoxy group is independently F, Cl, Br or I ; 和/或，RF或RG中，所述C1-C6烷基和所述卤素取代的C1-C6烷基中的C1-C6烷基独立地为C1-C3烷基，例如甲基、乙基、正丙基或异丙基；And/or, in R F or R G , the C1-C6 alkyl group in the C1-C6 alkyl group and the halogen-substituted C1-C6 alkyl group is independently a C1-C3 alkyl group, such as methyl, ethyl radical, n-propyl or isopropyl; 和/或，RF或RG中，所述卤素取代的C1-C6烷基中卤素的取代个数为1～6个；And/or, in R F or R G , the number of halogen substitutions in the halogen-substituted C1-C6 alkyl group is 1 to 6; 和/或，RF或RG中，所述C1-C6烷氧基和所述卤素取代的C1-C6烷氧基中的C1-C6烷氧基独立地为C1-C3烷氧基，例如甲氧基、乙氧基、正丙氧基或异丙氧基；And/or, in R F or R G , the C1-C6 alkoxy in the C1-C6 alkoxy and the halogen-substituted C1-C6 alkoxy is independently a C1-C3 alkoxy, for example Methoxy, ethoxy, n-propoxy or isopropoxy; 和/或，RF或RG中，所述卤素取代的C1-C6烷氧基中卤素的取代个数为1～6个；And/or, in R F or R G , the number of halogen substitutions in the halogen-substituted C1-C6 alkoxy group is 1 to 6; 和/或，RF或RG中，所述C6-C10芳基为苯基或萘基；And/or, in R F or R G , the C6-C10 aryl group is phenyl or naphthyl; 和/或，R10或R11中，所述C1-C3烷基为甲基、乙基、正丙基或异丙基；And/or, in R 10 or R 11 , the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl; 和/或，R7、R8或R9中，所述卤素取代的C1-C6烷基中的卤素为F、Cl、Br或I；And/or, in R 7 , R 8 or R 9 , the halogen in the halogen-substituted C1-C6 alkyl group is F, Cl, Br or I; 和/或，R7、R8或R9中，所述C1-C10烷基和所述卤素取代的C1-C10烷基中的C1-C10烷基独立地为C1-C6烷基，例如C1-C3烷基，再例如甲基、乙基、正丙基或异丙基；And/or, in R 7 , R 8 or R 9 , the C1-C10 alkyl group in the C1-C10 alkyl group and the halogen-substituted C1-C10 alkyl group is independently a C1-C6 alkyl group, such as C1 -C3 alkyl, for example methyl, ethyl, n-propyl or isopropyl; 和/或，R7、R8或R9中，所述卤素取代的C1-C10烷基中卤素的取代个数为1～6个；And/or, in R 7 , R 8 or R 9 , the number of halogen substitutions in the halogen-substituted C1-C10 alkyl group is 1-6; 和/或，R7、R8或R9中，所述C1-C10烷氧基为C1-C6烷氧基，例如C1-C3烷氧基，再例如甲氧基、乙氧基、正丙氧基或异丙氧基；And/or, in R 7 , R 8 or R 9 , the C1-C10 alkoxy group is a C1-C6 alkoxy group, such as a C1-C3 alkoxy group, and another example is methoxy, ethoxy, n-propyl oxy or isopropoxy; 和/或，R7、R8或R9中，所述C6-C10芳基和所述RE取代的C6-C10芳基中的C6-C10芳基为苯基或萘基；And/or, in R 7 , R 8 or R 9 , the C6-C10 aryl group in the C6-C10 aryl group and the C6-C10 aryl group substituted by the R E is phenyl or naphthyl; 和/或，R7、R8或R9中，所述“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”为“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5-10元杂芳基”，例如呋喃基、吡啶基或噻吩基；And/or, in R 7 , R 8 or R 9 , the "5-12-membered heteroaryl group containing 1-4 heteroatoms, the heteroatoms being one or more of O, S and N" is "5-10-membered heteroaryl containing 1-2 heteroatoms, the heteroatoms being one or more of O, S and N", such as furanyl, pyridyl or thienyl; 和/或，RE中，所述卤素、所述卤素取代的C1-C3烷基和所述卤素取代的C1-C3烷氧基中的卤素独立地为F、Cl、Br或I；And/or, in R E , the halogen in the halogen, the halogen-substituted C1-C3 alkyl group and the halogen-substituted C1-C3 alkoxy group is independently F, Cl, Br or I; 和/或，RE中，所述C1-C3烷基和所述卤素取代的C1-C3烷基中的C1-C3烷基独立地为甲基、乙基、正丙基或异丙基；And/or, in R E , the C1-C3 alkyl group in the C1-C3 alkyl group and the halogen-substituted C1-C3 alkyl group is independently methyl, ethyl, n-propyl or isopropyl; 和/或，RE中，所述卤素取代的C1-C3烷基中卤素的取代个数为1～6个；And/or, in R E , the number of halogen substitutions in the halogen-substituted C1-C3 alkyl group is 1-6; 和/或，RE中，所述C1-C3烷氧基和所述卤素取代的C1-C3烷氧基中的C1-C3烷氧基独立地为甲氧基、乙氧基、正丙氧基或异丙氧基；And/or, in R E , the C1-C3 alkoxy in the C1-C3 alkoxy and the halogen-substituted C1-C3 alkoxy is independently methoxy, ethoxy, n-propoxy radical or isopropoxy; 和/或，RE中，所述卤素取代的C1-C3烷氧基中卤素的取代个数为1～6个；And/or, in R E , the number of halogen substitutions in the halogen-substituted C1-C3 alkoxy group is 1-6; 和/或，R12或R13中，所述C1-C3烷基为甲基、乙基、正丙基或异丙基，例如甲基或乙基；And/or, in R 12 or R 13 , the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl, such as methyl or ethyl; 和/或，当R7、R8和R9的定义为如(ii)所述时，所述4-6元环烷基为5-6元环烷基，例如环戊烷或环己烷；and/or, when R 7 , R 8 and R 9 are defined as described in (ii), the 4-6 membered cycloalkyl group is a 5-6 membered cycloalkyl group such as cyclopentane or cyclohexane ; 和/或，当R7、R8和R9的定义为如(iii)所述时，所述“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5～7元杂环烯基”和所述R7A取代的“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5～7元杂环烯基”中的“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5～7元杂环烯基”为“含1～2个杂原子，杂原子为O和/或N的5～6元杂环烯基”，例如
Figure FDA0002375181160000071
And/or, when R 7 , R 8 and R 9 are defined as described in (iii), the "containing 1 to 2 heteroatoms, the heteroatoms are one or more of O, S and N" 5-7-membered heterocycloalkenyl" and the R 7A substituted "containing 1-2 heteroatoms, the heteroatoms are one or more of O, S and N. The 5-7-membered heterocycloalkenyl "Contains 1-2 heteroatoms, the heteroatoms are one or more of O, S and N. The 5- to 7-membered heterocycloalkenyl" is "contains 1-2 heteroatoms, and the heteroatoms are 5-6 membered heterocycloalkenyl of O and/or N", for example
Figure FDA0002375181160000071
 和/或，所述R7A取代的“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5～7元杂环烯基”中所述R7A的取代个数为1～3个，各R7A相同或不同；And/or, in the R 7A substituted "5- to 7 -membered heterocycloalkenyl group containing 1-2 heteroatoms, the heteroatom is one or more of O, S and N" The number of substitutions is 1 to 3, and each R 7A is the same or different; 和/或，所述R7A中，所述C1-C3烷基为甲基、乙基、正丙基或异丙基，例如甲基或乙基；And/or, in the R 7A , the C1-C3 alkyl group is methyl, ethyl, n-propyl or isopropyl, such as methyl or ethyl; 和/或，所述R7A取代的“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5～7元杂环烯基”为
Figure FDA0002375181160000072
And/or, the "5- to 7-membered heterocycloalkenyl group containing 1-2 heteroatoms, the heteroatoms being one or more of O, S and N" substituted by R 7A is:
Figure FDA0002375181160000072
 和/或，当R7、R8和R9的定义为如(iii)所述时，所述5～7元环烯基为5～6元环烯基，例如
Figure FDA0002375181160000073
And/or, when R 7 , R 8 and R 9 are defined as described in (iii), the 5-7 membered cycloalkenyl is a 5-6 membered cycloalkenyl, for example
Figure FDA0002375181160000073
 5.如权利要求1所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，R5A为卤素、硝基、-NHMs或
Figure FDA0002375181160000074
5. the preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 1 is characterized in that, R 5A is halogen, nitro, -NHMs or
Figure FDA0002375181160000074
 和/或，RA为卤素、乙酰氧基、C1-C3烷氧基、-NPhth或-COOR6；and/or, R A is halogen, acetoxy, C1-C3 alkoxy, -NPhth or -COOR 6 ; 和/或，RB为卤素或“含1个或2个杂原子，杂原子为O和/或N的3-6元杂环烷基”；and/or, R B is halogen or "3-6 membered heterocycloalkyl containing 1 or 2 heteroatoms, where the heteroatoms are O and/or N"; 和/或，所述C1-C3烷基取代的5～6元杂环烷基为
Figure FDA0002375181160000075
And/or, the C1-C3 alkyl substituted 5-6 membered heterocycloalkyl is
Figure FDA0002375181160000075
 和/或，RF或RG中，所述卤素取代的C1-C6烷基为-CF3；And/or, in R F or R G , the C1-C6 alkyl group substituted by the halogen is -CF 3 ; 和/或，RF或RG中，所述卤素取代的C1-C6烷氧基为-OCF3；And/or, in R F or R G , the halogen-substituted C1-C6 alkoxy group is -OCF 3 ; 和/或，R7、R8或R9中，所述卤素取代的C1-C10烷基为-CF3；And/or, in R 7 , R 8 or R 9 , the halogen-substituted C1-C10 alkyl group is -CF 3 ; 和/或，RE中，所述卤素取代的C1-C3烷基为-CF3；And/or, in R E , the C1-C3 alkyl group substituted by the halogen is -CF 3 ; 和/或，RE中，所述卤素取代的C1-C3烷氧基为-OCF3；And/or, in R E , the C1-C3 alkoxy group substituted by the halogen is -OCF 3 ; 和/或，R7、R8或R9中，所述RE取代的C6-C10芳基为卤素取代的C6-C10芳基，例如卤素取代的苯基。And/or, in R 7 , R 8 or R 9 , the R E -substituted C6-C10 aryl group is a halogen-substituted C6-C10 aryl group, such as a halogen-substituted phenyl group. 6.如权利要求1所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，X为S；6. the preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 1, is characterized in that, X is S; 和/或，R为卤素、C1-C10烷基、RA取代的C1-C10烷基、C1-C10烷氧基、RB取代的C1-C10烷氧基、“含1个或2个杂原子，杂原子为O和/或N的3-6元杂环烷基”、5-6元环烷基、-COOR4、-OR5、C6-C10芳基、RC取代的C6-C10芳基、苄基、
Figure FDA0002375181160000081
Figure FDA0002375181160000082
And/or, R is halogen, C1-C10 alkyl, R A substituted C1-C10 alkyl, C1-C10 alkoxy, R B substituted C1-C10 alkoxy, "containing 1 or 2 hetero Atom, 3-6-membered heterocycloalkyl "where the heteroatom is O and/or N", 5-6-membered cycloalkyl, -COOR 4 , -OR 5 , C6-C10 aryl, R C substituted C6-C10 Aryl, benzyl,
Figure FDA0002375181160000081
Figure FDA0002375181160000082
 和/或，R1和R2为H，或者OR1和OR2与它们共同连接的硼原子一起形成C1-C3烷基取代的5～6元杂环烷基，例如形成
Figure FDA0002375181160000083
And/or, R 1 and R 2 are H, or OR 1 and OR 2 together with the boron atom to which they are attached together form a C1-C3 alkyl-substituted 5-6 membered heterocycloalkyl, for example, forming
Figure FDA0002375181160000083
 和/或，RF为卤素、硝基、TMS、乙酰基、-SR10、-COOR11、C1-C6烷基、卤素取代的C1-C6烷基、C1-C6烷氧基、卤素取代的C1-C6烷氧基或C6-C10芳基；and/or, R F is halogen, nitro, TMS, acetyl, -SR 10 , -COOR 11 , C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C1-C6 alkoxy, halogen-substituted C1-C6 alkoxy or C6-C10 aryl; 和/或，RG为卤素；and/or, R G is halogen; 和/或，当R7、R8和R9的定义为如(i)所述时，R7、R8和R9独立地为H、C1-C10烷基、C6-C10芳基、RE取代的C6-C10芳基、“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5-10元杂芳基”或-COOR12，且R7、R8和R9不同时为H；较佳地，当R7、R8和R9的定义为如(i)所述时，R7为H，R8和R9独立地为H、C6-C10芳基、卤素取代的C6-C10芳基、“含1～2个杂原子，杂原子为O、S和N中的一种或多种的5-10元杂芳基”或-COOR12，且R8和R9不同时为H。and/or, when R 7 , R 8 and R 9 are defined as described in (i), R 7 , R 8 and R 9 are independently H, C1-C10 alkyl, C6-C10 aryl, R E -substituted C6-C10 aryl, "5-10-membered heteroaryl containing 1-2 heteroatoms, the heteroatoms being one or more of O, S and N" or -COOR 12 , and R 7 , R 8 and R 9 are not H at the same time; preferably, when R 7 , R 8 and R 9 are defined as described in (i), R 7 is H, R 8 and R 9 are independently H, C6-C10 aryl, halogen-substituted C6-C10 aryl, "5-10-membered heteroaryl containing 1-2 heteroatoms, the heteroatoms being one or more of O, S and N" or - COOR 12 , and R 8 and R 9 are not H at the same time. 7.如权利要求1所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，X为S；R为卤素、C1-C10烷基、RA取代的C1-C10烷基、C1-C10烷氧基、RB取代的C1-C10烷氧基、“含1个或2个杂原子，杂原子为O和/或N的3-6元杂环烷基”、5-6元环烷基、-COOR4、-OR5、C6-C10芳基、RC取代的C6-C10芳基、苄基、
Figure FDA0002375181160000091
Figure FDA0002375181160000092
7. the preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 1, it is characterised in that X is S; R is halogen, C1-C10 alkyl, RA substituted C1 -C10 alkyl, C1-C10 alkoxy, R B substituted C1-C10 alkoxy, "3-6 membered heterocycloalkyl containing 1 or 2 heteroatoms, the heteroatoms are O and/or N ", 5-6 membered cycloalkyl, -COOR 4 , -OR 5 , C6-C10 aryl, R C substituted C6-C10 aryl, benzyl,
Figure FDA0002375181160000091
Figure FDA0002375181160000092
 或者，R1和R2为H，R3为C6-C10芳基、RF取代的C6-C10芳基、“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”或RG取代的“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”；Or, R 1 and R 2 are H, R 3 is C6-C10 aryl, R F substituted C6-C10 aryl, "containing 1 to 4 heteroatoms, and the heteroatom is one of O, S and N. or more 5-12-membered heteroaryl groups" or R G substituted "5-12-membered heteroaryl groups containing 1 to 4 heteroatoms, the heteroatoms being one or more of O, S and N"; 或者，OR1和OR2与它们共同连接的硼原子一起形成C1-C3烷基取代的5～6元杂环烷基(例如
Figure FDA0002375181160000093
)；R3为C6-C10芳基、RF取代的C6-C10芳基、“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”或RG取代的“含1～4个杂原子，杂原子为O、S和N中的一种或多种的5-12元杂芳基”；Alternatively, OR 1 and OR 2 together with the boron atom to which they are commonly attached form a C1-C3 alkyl substituted 5-6 membered heterocycloalkyl (eg
Figure FDA0002375181160000093
); R 3 is a C6-C10 aryl group, a C6-C10 aryl group substituted by R F , a 5-12-membered group containing 1 to 4 heteroatoms, and the heteroatoms are one or more of O, S and N "Heteroaryl" or R G -substituted "5-12-membered heteroaryl containing 1 to 4 heteroatoms, and the heteroatoms are one or more of O, S and N"; 或者，OR1和OR2与它们共同连接的硼原子一起形成C1-C3烷基取代的5～6元杂环烷基(例如
Figure FDA0002375181160000094
)；R3为
Figure FDA0002375181160000095
Alternatively, OR 1 and OR 2 together with the boron atom to which they are commonly attached form a C1-C3 alkyl substituted 5-6 membered heterocycloalkyl (eg
Figure FDA0002375181160000094
); R 3 is
Figure FDA0002375181160000095
 8.如权利要求1所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，所述如式(II)所示的芳基锍盐选自如下任一结构：8. the preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 1, is characterized in that, described aryl sulfonium salt shown in formula (II) is selected from following any structure:
Figure FDA0002375181160000096
Figure FDA0002375181160000096
Figure FDA0002375181160000101
Figure FDA0002375181160000101
Figure FDA0002375181160000111
Figure FDA0002375181160000111
 或者，所述如式(III)所示的硼化物选自如下任一结构：Alternatively, the boride shown in formula (III) is selected from any of the following structures:
Figure FDA0002375181160000112
Figure FDA0002375181160000112
Figure FDA0002375181160000121
Figure FDA0002375181160000121
 9.如权利要求1～8任一项所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，所述如式(I)所示的对位取代芳基化合物的制备方法还包括以下步骤：9. The preparation method of the para-substituted aryl compound represented by formula (I) according to any one of claims 1 to 8, wherein the para-substituted aryl compound represented by formula (I) The preparation method of base compound also comprises the following steps: 溶剂中，如式(IV)所示的芳烃类化合物、如式(V)所示的锍盐化试剂和“三氟甲磺酸酐、三氟乙酸酐和HBF4·OEt2中的一种或多种”进行锍盐化反应，得如式(II)所示的芳基锍盐，即可；In the solvent, the aromatic hydrocarbon compound shown in formula (IV), the sulfonium salting reagent shown in formula (V) and one of "trifluoromethanesulfonic anhydride, trifluoroacetic anhydride and HBF 4 ·OEt 2 or A variety of "carries out the sulfonium salting reaction to obtain the aryl sulfonium salt shown in formula (II), and get final product;
Figure FDA0002375181160000122
Figure FDA0002375181160000122
 其中，R、X和Y的定义如权利要求1～8任一项所述。Wherein, the definitions of R, X and Y are as described in any one of claims 1-8. 10.如权利要求9所述的如式(I)所示的对位取代芳基化合物的制备方法，其特征在于，所述如式(II)所示的芳基锍盐的制备方法中，所述溶剂为卤代烷烃类溶剂和/或腈类溶剂，例如二氯甲烷或乙腈；10. The preparation method of the para-substituted aryl compound shown in formula (I) as claimed in claim 9, wherein, in the preparation method of the aryl sulfonium salt shown in formula (II), The solvent is a halogenated alkane-based solvent and/or a nitrile-based solvent, such as dichloromethane or acetonitrile; 和/或，所述如式(II)所示的芳基锍盐的制备方法中，所述如式(IV)所示的芳烃类化合物与所述溶剂的摩尔体积比为0.01-5.0mol/L，例如0.2mol/L；And/or, in the preparation method of the arylsulfonium salt shown in the formula (II), the molar volume ratio of the aromatic hydrocarbon compound shown in the formula (IV) to the solvent is 0.01-5.0mol/ L, such as 0.2mol/L; 和/或，所述如式(II)所示的芳基锍盐的制备方法中，所述如式(IV)所示的芳烃类化合物与所述“三氟甲磺酸酐、三氟乙酸酐和HBF4·OEt2中的一种或多种”的摩尔比为1：(1-3)，例如1:1.2；And/or, in the preparation method of the arylsulfonium salt shown in the formula (II), the aromatic hydrocarbon compound shown in the formula (IV) and the "trifluoromethanesulfonic anhydride, trifluoroacetic anhydride" and one or more of HBF 4 ·OEt 2 " in a molar ratio of 1:(1-3), such as 1:1.2; 和/或，所述如式(II)所示的芳基锍盐的制备方法中，所述如式(IV)所示的芳烃类化合物与如式(V)所示的锍盐化试剂的摩尔比为1：(1-3)，例如1:1.2；And/or, in the preparation method of the aryl sulfonium salt shown in the formula (II), the aromatic hydrocarbon compound shown in the formula (IV) and the sulfonium salt reagent shown in the formula (V) are mixed. The molar ratio is 1:(1-3), such as 1:1.2; 和/或，所述如式(II)所示的芳基锍盐的制备方法中，所述如式(II)所示的芳基锍盐的制备方法在惰性气氛下进行，所述惰性气氛可为氮气或氩气；And/or, in the preparation method of the arylsulfonium salt shown in the formula (II), the preparation method of the arylsulfonium salt shown in the formula (II) is carried out under an inert atmosphere, and the inert atmosphere Can be nitrogen or argon; 和/或，所述如式(II)所示的芳基锍盐的制备方法中，所述锍盐化反应的温度为-40℃-35℃；例如在-40℃中反应10-40min后升温至25-35℃反应50-70min；And/or, in the preparation method of the aryl sulfonium salt represented by the formula (II), the temperature of the sulfonium salt reaction is -40°C-35°C; for example, after the reaction at -40°C for 10-40min Warm up to 25-35°C for 50-70min; 和/或，所述如式(II)所示的芳基锍盐的制备方法中，所述锍盐化反应的时间为1-3小时，例如1.5小时；And/or, in the preparation method of the aryl sulfonium salt shown in the formula (II), the time of the sulfonium salt reaction is 1-3 hours, such as 1.5 hours; 和/或，所述如式(II)所示的芳基锍盐的制备方法中，所述锍盐化反应无需进行后处理，直接进行所述偶联反应。And/or, in the preparation method of the aryl sulfonium salt represented by the formula (II), the sulfonium salt formation reaction does not require post-treatment, and the coupling reaction is directly performed.
CN202010063307.1A 2020-01-20 2020-01-20 Preparation method of para-substituted aryl compound Active CN111187130B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010063307.1A CN111187130B (en) 2020-01-20 2020-01-20 Preparation method of para-substituted aryl compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010063307.1A CN111187130B (en) 2020-01-20 2020-01-20 Preparation method of para-substituted aryl compound

Publications (2)

Publication Number Publication Date
CN111187130A true CN111187130A (en) 2020-05-22
CN111187130B CN111187130B (en) 2021-12-14

Family

ID=70706491

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010063307.1A Active CN111187130B (en) 2020-01-20 2020-01-20 Preparation method of para-substituted aryl compound

Country Status (1)

Country Link
CN (1) CN111187130B (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113372186A (en) * 2021-06-17 2021-09-10 湖南大学 Method for synthesizing biaryl compound
JP2022021311A (en) * 2020-07-21 2022-02-02 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP2022021313A (en) * 2020-07-21 2022-02-02 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025021A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025022A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP2022025026A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025024A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP2022025023A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025025A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP2022028616A (en) * 2020-08-03 2022-02-16 住友化学株式会社 Carboxylate, carboxylic acid generator, resin, resist composition and method for producing resist pattern
JP2022028615A (en) * 2020-08-03 2022-02-16 住友化学株式会社 Salt, acid generator, resin, resist composition and method for producing resist pattern
JP2022059112A (en) * 2020-10-01 2022-04-13 信越化学工業株式会社 Sulfonium salt, chemically amplified resist composition and pattern forming method
CN114634481A (en) * 2022-03-24 2022-06-17 中国科学院上海有机化学研究所 Method for synthesizing aryl and alkenyl sulfonium salt
CN117209342A (en) * 2023-07-26 2023-12-12 浙江大学 Synthesis method of para-substituted biphenyl compounds
CN118852020A (en) * 2024-09-23 2024-10-29 南京桦冠生物技术有限公司 A method for preparing high-purity medicinal bifonazole

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8546607B2 (en) * 2009-09-25 2013-10-01 The Regents Of The University Of California Cross-coupling of phenolic derivatives
WO2017081133A1 (en) * 2015-11-10 2017-05-18 Ppp Chemistry B.V. Process for preparing 2,6-substituted phenols

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8546607B2 (en) * 2009-09-25 2013-10-01 The Regents Of The University Of California Cross-coupling of phenolic derivatives
WO2017081133A1 (en) * 2015-11-10 2017-05-18 Ppp Chemistry B.V. Process for preparing 2,6-substituted phenols

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7696243B2 (en) 2020-07-21 2025-06-20 住友化学株式会社 Carboxylic acid salt, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022021311A (en) * 2020-07-21 2022-02-02 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP2022021313A (en) * 2020-07-21 2022-02-02 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP7728113B2 (en) 2020-07-21 2025-08-22 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP7686481B2 (en) 2020-07-28 2025-06-02 住友化学株式会社 Carboxylic acid salt, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025026A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025024A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP2022025023A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025025A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP7686480B2 (en) 2020-07-28 2025-06-02 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP7686479B2 (en) 2020-07-28 2025-06-02 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP7686478B2 (en) 2020-07-28 2025-06-02 住友化学株式会社 Carboxylic acid salt, carboxylic acid generator, resist composition and method for producing resist pattern
JP2022025021A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Carboxylate, carboxylic acid generator, resist composition and method for producing resist pattern
JP7691871B2 (en) 2020-07-28 2025-06-12 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP2022025022A (en) * 2020-07-28 2022-02-09 住友化学株式会社 Salt, acid generator, resist composition and method for producing resist pattern
JP7691872B2 (en) 2020-07-28 2025-06-12 住友化学株式会社 Carboxylic acid salt, carboxylic acid generator, resist composition and method for producing resist pattern
JP7691875B2 (en) 2020-08-03 2025-06-12 住友化学株式会社 Carboxylic acid salt, carboxylic acid generator, resin, resist composition and method for producing resist pattern
JP7699985B2 (en) 2020-08-03 2025-06-30 住友化学株式会社 Salt, acid generator, resin, resist composition and method for producing resist pattern
JP2022028615A (en) * 2020-08-03 2022-02-16 住友化学株式会社 Salt, acid generator, resin, resist composition and method for producing resist pattern
JP2022028616A (en) * 2020-08-03 2022-02-16 住友化学株式会社 Carboxylate, carboxylic acid generator, resin, resist composition and method for producing resist pattern
JP2022059112A (en) * 2020-10-01 2022-04-13 信越化学工業株式会社 Sulfonium salt, chemically amplified resist composition and pattern forming method
US12216401B2 (en) 2020-10-01 2025-02-04 Shin-Etsu Chemical Co., Ltd. Sulfonium salt, chemically amplified resist composition, and patterning process
JP7491173B2 (en) 2020-10-01 2024-05-28 信越化学工業株式会社 Sulfonium salt, chemically amplified resist composition and pattern forming method
CN113372186A (en) * 2021-06-17 2021-09-10 湖南大学 Method for synthesizing biaryl compound
CN113372186B (en) * 2021-06-17 2023-10-20 湖南大学 Method for synthesizing biaryl compound
CN114634481B (en) * 2022-03-24 2023-10-27 中国科学院上海有机化学研究所 A method for synthesizing aryl and alkenyl sulfonium salts
CN114634481A (en) * 2022-03-24 2022-06-17 中国科学院上海有机化学研究所 Method for synthesizing aryl and alkenyl sulfonium salt
CN117209342A (en) * 2023-07-26 2023-12-12 浙江大学 Synthesis method of para-substituted biphenyl compounds
CN117209342B (en) * 2023-07-26 2025-07-11 浙江大学 Synthesis method of para-substituted biphenyl compounds
CN118852020B (en) * 2024-09-23 2025-01-28 南京桦冠生物技术有限公司 A method for preparing high-purity medicinal bifonazole
CN118852020A (en) * 2024-09-23 2024-10-29 南京桦冠生物技术有限公司 A method for preparing high-purity medicinal bifonazole

Also Published As

Publication number Publication date
CN111187130B (en) 2021-12-14

Similar Documents

Publication Publication Date Title
CN111187130A (en) Process for producing para-substituted aryl compound
Yuen et al. Deprotection of pinacolyl boronate esters via hydrolysis of intermediate potassium trifluoroborates
Kondo et al. Specific complexation of disaccharides with diphenyl-3, 3′-diboronic acid that can be detected by circular dichroism
Zhang et al. Redox-neutral cyanoalkylation/cyclization of olefinic 1, 3-dicarbonyls with cycloketone oxime esters: access to cyanoalkylated dihydrofurans
CN113582915B (en) Synthesis method of 4-substituted pyridine compound
Li et al. Diastereodivergent synthesis of cyclopropanes via on-water [2+ 1] annulations of diazo compounds with electron-deficient alkenes
CN115010600B (en) A method for synthesizing polyfluoroaryl carboxylic acid compounds based on the carboxylation reaction of aryl carbon-fluorine bonds
Wu et al. One-carbon homologation of arylboronic acids: a convenient approach to the synthesis of pinacol benzylboronates
Bigi et al. Homogeneous versus heterogeneous approach to the catalytic desymmetrisation of meso-anhydrides promoted by cinchona alkaloids
CN107488089A (en) Have axial chirality and the high optical activity allenic compound and its construction method of central chirality and application concurrently
CN106946648B (en) Fluorene compound and method for producing fluorene compound
CN109293700A (en) Chiral bisphosphine ligand, its preparation method, intermediate and application
CN108164493B (en) A kind of aromatic polyketone compound and preparation method thereof
CN117247370A (en) Method for synthesizing thioflavonoids based on alkyne thiocarboxyl
CN112125843B (en) A kind of preparation method of 3-hydroxymethyl-4-phenyl-3,4-dihydroquinolinone compound
CN102311381A (en) Method for synthesizing alpha ethyl ester derivative
Ohtsuki et al. H‐* BEA Zeolite‐Catalyzed Nucleophilic Substitution in Allyl Alcohols Using Sulfonamides, Amides, and Anilines
Sośnicki Efficient synthesis of 5-functionalised 2-methoxypyridines and their transformation to bicyclic δ-lactams, both accessed using magnesium ‘ate’complexes as key reagents
Chumnanvej et al. Convenient synthesis of α-nitrooximes mediated by OXONE®
Wienhold et al. Synthesis of functionalized benzoboroxoles for the construction of boronolectins
CN115160348B (en) A method for direct borylation of aromatic C-H bonds under light without metal catalysis
Lin et al. CuO‐Catalyzed 1, 3‐Addition of Diaryliodonium Triflates to Diazo Esters for the Stereoselective Synthesis of Triflate‐Substituted β‐Aryloxyl Acrylates
CN112479898A (en) Divalent manganese catalyzed arylamine ortho-olefination reaction method
CN116715622B (en) Synthesis method of 2- (2-arylbutyl) pyridine compound
Salomone et al. Synthesis of Conjugated tri (hetero) aryl derivatives based on one-pot double suzuki-miyaura couplings using bifunctional dipotassium phenylene-1, 4-bis (trifluoroborate)

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant