CN119948008A

CN119948008A - A method for preparing condensed ring aromatic amines using isonitrile and cyclopropene as raw materials

Info

Publication number: CN119948008A
Application number: CN202280098051.5A
Authority: CN
Inventors: 何振宇; 黄建强
Original assignee: Southern University of Science and Technology
Current assignee: Southern University of Science and Technology
Priority date: 2022-07-15
Filing date: 2022-07-15
Publication date: 2025-05-06
Also published as: WO2024011559A1

Abstract

The application discloses a method for preparing condensed ring aromatic amine from isonitrile and cyclopropene, which has the following reaction formula:

Description

Method for preparing condensed ring aromatic amine by taking isonitrile and cyclopropene as raw materials

Technical Field

The application relates to the technical field of organic synthesis, in particular to a method for preparing condensed ring arylamine by taking isonitrile and cyclopropene as raw materials.

Background

The synthesis of condensed aromatic amines is one of the most important research matters in organic synthetic chemistry, and they are the core structures of many important functional materials and bioactive molecules. The condensed ring arylamine compounds can be used as starting materials for the preparation of various materials by subsequent transformations, such as electrophilic and nucleophilic aryl substitution, aryl hydrocarbon activation and dearomatization reactions.

The high cost and complex preparation methods of arylamine compounds have hindered the full exploitation of the potential of such compounds. Most of the condensed aromatic amines are obtained from natural resources such as coal tar or petroleum at present, and the structural diversity is very limited.

At present, the synthesis of condensed ring aromatic amine is based on intramolecular reaction (such as cycloisomerism), which seriously influences the development of related fields such as pharmaceutical chemistry, combinatorial chemistry and the like and the optimization of functional materials. Therefore, there is a need to develop intermolecular methods for efficient synthesis of polyfunctional condensed ring aromatic amines, preferably starting from readily available starting materials.

Disclosure of Invention

In view of the deficiencies of the prior art, it is an object of the present invention to provide a process for preparing a compound of formula (III) from a compound of formula (I) and a compound of formula (II) in the presence of a carbene and a transition metal catalyst or precursor thereof,

It is characterized in that the method comprises the steps of,

Ar ¹ is optionally one of aryl, heteroaryl and alkenyl,

R ¹、R² and R ³ may independently optionally be hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or one of the metalloids.

The substituents on the compounds of formula (I) are optionally alkylene chain linked.

R ⁴ is optionally one of alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid and is attached to a substituent on the compound of formula (I).

Ar ² is optionally aryl, heteroaryl (substituted aryl and heteroaryl from Ar ¹), or optionally aliphatic (substituted alkenyl from Ar ¹).

The transition metal catalyst is optionally of groups 3-12.

The carbene optionally contains any member of the divalent carbon atoms.

Detailed Description

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present description. One skilled in the relevant art will recognize, however, that the invention can be practiced with other methods, components, materials, and so forth, without one or more of the specific details.

Throughout the specification and the appended claims, unless the context requires otherwise, the word "comprise" and variations such as "comprises" and "comprising" will be construed in an open, inclusive sense, i.e. "including but not limited to.

Reference throughout this specification to "one embodiment," or "in another embodiment," or "some embodiments," or "in some embodiments," means that a particular reference feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases "in one embodiment," "in an embodiment," "in another embodiment," or "in some embodiments" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

It should be noted that, in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. In the present application, the use of "or" means "and/or" unless otherwise indicated.

Some of the chemical groups described herein are preceded by shorthand notation that indicates the total number of carbon atoms found in the chemical group indicated. For example, C ₇-C₁₂ alkyl refers to an alkyl group as defined below having a total of 7 to 12 carbon atoms, and C ₄-C₁₂ cycloalkyl refers to a cycloalkyl group as defined below having a total of 4 to 12 carbon atoms. The total number of carbons in the shorthand notation does not include carbons that may be present in a substituent of the group.

As used herein, "C _m to C _n" or "C _{m To the point of n}", wherein "m" and "n" are integers, refer to the number of carbon atoms in an alkyl, alkenyl or alkynyl group or the number of carbon atoms in a cycloalkyl or cycloalkenyl ring. That is, the ring of an alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl group may contain carbon atoms from "m" to "n" (including "m" and "n"). Thus, for example, a "C ₁ to C ₄ alkyl" group refers to all alkyl groups having 1 to 4 carbons, i.e., CH₃-、CH₃CH₂-、CH₃CH₂CH₂-、(CH₃)₂CH-、CH₃CH₂CH₂CH₂-、CH₃CH₂CH(CH₃)- and (CH ₃)₃ c— if "m" and "n" are not specified for alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl, then the broadest scope described in these definitions is assumed.

The following terms, therefore, are used in the specification and the appended claims, unless indicated to the contrary, all have the meanings indicated below:

The term "alkyl" as used herein alone or as part of a group refers to any unbranched or branched, substituted or unsubstituted saturated hydrocarbon group. The alkyl moiety may be branched or straight chain. Alkyl groups may have from 1 to 20 carbon atoms (whenever present herein, a numerical range such as "1 to 20" refers to each integer within a given range; e.g., "1 to 20 carbon atoms" refers to an alkyl group that may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although the present definition also covers the occurrence of the term "alkyl", where no numerical range is specified). The alkyl group may also be a medium size alkyl group having 1 to 10 carbon atoms. The alkyl group may also be a lower alkyl group having 1 to 5 carbon atoms. Alkyl may be referred to as "C ₁-C₄ alkyl" or similar names. By way of example only, a "C ₁-C₄ alkyl" means having 1 to 4 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

Alkyl groups may be substituted or unsubstituted. When substituted, the substituents are one or more groups independently selected from the group consisting of substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaryloxy, heterocyclyl, heterocyclyloxy, heteroalicyclic, hydroxy, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, acyl, thiol, substituted or unsubstituted thioalkoxy, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, acylalkyl, acylamino, acyloxy, aminoacyl, aminoacyloxy, oxyamido, keto, thioketo, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, N-acylamino, S-sulfinylamino, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, and monosubstituted SO-35, including substituted SO-35-substituted SO 35-substituted aryl.

Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, and the like. When a substituent is described as "optional," the substituent may be substituted with one or more of the substituents described above.

The term "alkenyl" as used herein alone or as part of a group refers to a straight or branched hydrocarbon chain group consisting of only carbon and hydrogen atoms, containing at least one double bond, having 2 to 12 carbon atoms, preferably 2 to 8 carbon atoms, and being attached to the remainder of the molecule by a single bond, such as ethenyl, propenyl, butenyl, pentenyl, penta-1, 4-dienyl, cyclohexenyl, and the like.

The term "alkynyl", as used herein alone or as part of a group, refers to a straight or branched hydrocarbon chain group consisting of only carbon and hydrogen atoms, containing at least one triple bond, having 2 to 12 carbon atoms, preferably 2 to 8 carbon atoms, and being attached to the remainder of the molecule by single bonds, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

The term "aryl" as used herein alone or as part of a group refers to a carbocyclic aromatic ring or ring system. Aryl groups may be unsubstituted or substituted. Furthermore, the term "aryl" includes fused ring systems wherein at least two aryl rings, or at least one aryl and at least one C _3-8 -cycloalkyl group, share at least one chemical bond. Some examples of "aryl" rings include optionally substituted phenyl, naphthyl, phenanthryl, anthracyl, tetrahydronaphthyl, fluorenyl, indenyl, and indanyl.

The term "aryl" refers to aromatic groups, including, for example, benzene-type groups, attached through one ring-forming carbon atom, and optionally bearing one or more substituents selected from the group consisting of heterocyclyl, heteroaryl, halogen, hydroxy, amino, cyano, nitro, alkylamido, acyl, C _1-6 -alkoxy, C _1-6 -alkyl, C _1-6 -hydroxyalkyl, C _1-6 -aminoalkyl, C _1-6 -alkylamino, alkylsulfinyl, alkylsulfonyl, sulfamoyl, or trifluoromethyl. Aryl groups may be optionally substituted in para, ortho and/or meta positions.

The term "heteroaryl" as used herein alone or as part of a group refers to a heterocyclic aromatic group in which one or more carbon atoms of the aromatic ring are replaced with one or more heteroatoms such as nitrogen, sulfur, and oxygen.

Furthermore, herein, the term "heteroaryl" includes fused ring systems in which at least one aromatic ring and at least one heteroaromatic ring, at least two heteroaromatic rings, at least one heteroaromatic ring and at least one heterocyclyl ring, or at least one heteroaromatic ring and at least one cycloalkyl ring share at least one bond.

The term "heteroaryl" is understood to refer to aromatic C _3-8 ring groups containing one oxygen or sulfur atom or up to four nitrogen atoms, or a combination of one oxygen or sulfur atom and up to two nitrogen atoms, as well as substituted and benzo-and pyrido-fused derivatives thereof, e.g., attached through a ring-forming carbon atom. Heteroaryl groups may bear one or more substituents selected from halogen, hydroxy, amino, cyano, nitro, alkylamido, acyl, C _1-6 -alkoxy, C _1-6 -alkyl, C _1-6 -hydroxyalkyl, C _1-6 -aminoalkyl, C _1-6 -alkylamino, alkylsulfinyl, alkylsulfonyl or trifluoromethyl. In some embodiments, heteroaryl groups may be five-and six-membered aromatic heterocyclic ring systems bearing 0,1, or 2 substituents, which may be the same or different from each other, selected from the list above.

Representative examples of heteroaryl groups include, but are not limited to, furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole, oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, benzothiazole, isothiazole, imidazole, benzimidazole, pyrazole, indazole, tetrazole, carbostyril, isoquinoline, pyridazine, pyrimidine, purine and pyrazine, furazan, 1,2, 3-oxadiazole, 1,2, 3-thiadiazole, 1,2, 4-thiadiazole, borozine, triazole, benzotriazole, pteridine, benzoxazole, oxadiazole, benzopyrazole, quinolizine, cinnoline, phthalazine, quinazoline and quinoxaline unsubstituted and mono-or di-substituted derivatives. In some embodiments, substituents are halogen, hydroxy, cyano, O-C _1-6 -alkyl, C _1-6 -alkyl, hydroxy-C _1-6 -alkyl, and amino-C _1-6 -alkyl.

The terms "optional," "optional," or "optionally" as used herein mean that the subsequently described event may or may not occur, and that the description includes both instances where the event or circumstance occurs and instances where it does not.

Unless otherwise indicated, when a substituent is considered "optional" it means that the substituent is a group that may be substituted with one or more groups selected independently and independently from morpholinoate, cycloalkyl, aryl, heteroaryl, heterocyclyl, heteroalicyclic, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-carbamoyl S-sulfonylamino, N-sulfonylamino, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethylsulfonyl, and amino, including mono-and di-substituted amino, and protected derivatives thereof.

For example, "optionally aryl" means that the aryl group may be substituted or unsubstituted, and that the description includes both substituted aryl groups and unsubstituted aryl groups.

The term "transition metal" as used herein refers to any element in the d-region of the periodic table of elements. This corresponds to groups 3 (IIIB) to 12 (IIB) of the periodic Table of the elements.

The term "ligand" in chemistry generally refers to an atom, ion, or molecule that is bound to a central metal, generally involving formally providing one or more electrons.

The term "carbene" as used herein refers to an organic molecule containing a carbon atom with six valence electrons and having the general formula RRC.

The term "alkylene" or "alkylene chain" as used herein alone or as part of a group refers to a straight or branched divalent hydrocarbon chain such as methylene, ethylene, propylene, n-butylene, etc., that connects the remainder of the molecule to a group consisting solely of carbon and hydrogen, free of unsaturated bonds, and having from 1 to 12 carbon atoms. The alkylene chain is linked to the rest of the molecule by a single bond and to the group by a single bond. The point of attachment of the alkylene chain to the remainder of the molecule and to the group may be through one carbon or any two carbons within the chain.

The term "alkenylene" or "alkenylene chain" as used herein alone or as part of a group refers to a straight or branched divalent hydrocarbon chain such as vinylidene, propenylene, n-butenyl, etc., linking the remainder of the molecule to a group consisting solely of carbon and hydrogen, containing at least one double bond and having from 2 to 12 carbon atoms. Alkenylene chains are attached to the remainder of the molecule by a single bond and to a group by a double bond or a single bond. The point of attachment of the alkenylene chain to the remainder of the molecule and to the group may be through one carbon or any two carbons within the chain.

The term "alkynylene" or "alkynylene chain" as used herein alone or as part of a group refers to a straight or branched divalent hydrocarbon chain, such as propynylene, n-butynylene, and the like, that connects the remainder of the molecule to a group consisting solely of carbon and hydrogen, containing at least one triple bond, and having from 2 to 12 carbon atoms. The alkynylene chain is attached to the remainder of the molecule by a single bond and to the group by a double bond or a single bond. The point of attachment of the alkynylene chain to the remainder of the molecule and to the group may be through one carbon or any two carbons within the chain.

The term "amine" as used herein refers to a compound comprising an amino group. The term "amino" as used herein alone or as part of a group refers to a substituted N-group.

Metalloids, or semi-metals, are terms used in chemistry to classify chemical elements. Almost every element in the periodic table can be referred to as a metal or a nonmetal, according to their general physical and chemical properties. However, a few elements are called metalloids. The term is not strictly defined, but is generally considered to be characteristic of metalloids in that (1) the metalloid often forms amphoteric oxides, and (2) the metalloid generally behaves as a semiconductor (B, si, ge).

The following elements are generally considered metalloids boron (B), silicon (Si), germanium (Ge), arsenic (As), antimony (Sb), tellurium (Te) and polonium (Po).

In one aspect, the present application relates to a process for preparing a compound of formula (III) from a compound of formula (I) and a compound of formula (II) in the presence of an N-heterocyclic carbene and a transition metal catalyst or precursor thereof,

It is characterized in that the method comprises the steps of,

Ar ¹ is optionally one of aryl, heteroaryl and alkenyl,

R ¹、R² and R ³ are independently optionally hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or one of the metalloids,

R ⁴ is optionally one of alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid and is optionally attached to a substituent on the compound of formula (I).

The transition metal catalyst is optionally of groups 3-12.

The carbenes are optionally substituted with one or more heteroatoms. When a cyclic carbene is used, the ring size is optionally a 4-12 membered ring.

In some embodiments of the application, ar ¹ is optionally substituted phenyl, naphthyl, phenanthryl, anthracyl, tetrahydronaphthyl, fluorenyl, alkenyl, indenyl, or indanyl.

In some embodiments of the application, the compounds of formula (I) are optionally cyclopropene and substituted derivatives thereof.

In some embodiments of the application, R ¹、R² and R ³ are independently optionally hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl, or metalloid.

In some embodiments of the application, the substituents on the compounds of formula (I) are optionally alkylene chain linked.

In some embodiments of the application, R ⁴ is optionally substituted alkyl, aryl, heteroaryl, alkenyl, alkynyl, or metalloid.

In some embodiments of the application, the compound of formula (II) is selected from isocyanides such as phenyl isocyanide, furanyl isocyanide, t-butyl isocyanide, and substituted derivatives thereof.

The transition metal catalyst of the present application may comprise any catalytic transition metal and/or catalyst precursor which, when introduced into the reaction vessel, and if desired, may be converted in situ into the active form, as well as into the active form of the catalyst involved in the reaction. In some embodiments of the application, the transition metal is optionally group 3-12.

Exemplary transition metals that may be used in the present application include, but are not limited to, scandium (SC), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), yttrium (Y), zirconium (Zr), niobium (Nb) molybdenum (Mo), technetium (TC), ruthenium (Ru), rhodium (Rh), palladium (PD), silver (Ag), cadmium (CD), hafnium (HF), tantalum (Ta), tungsten (W), rhenium (Re), osmium (OS), iridium (IR), platinum (Pt), gold (Au), mercury (Hg), du (Db), scale (SG), boron (BH), potassium (Hs), metal (Mt), dammstein (DS), renqin (Rg), and Uunbium (Uub).

In some embodiments of the application, the transition metal is selected from group 10.

In some embodiments of the application, the transition metal is selected from nickel (Ni), palladium (Pd), and platinum (Pt). In some embodiments of the application, the transition metal is nickel (Ni).

In some embodiments of the application, the ligand on the transition metal catalyst is selected from the group consisting of carbenes, heterocyclic carbenes (NHCs), dicarboxins, bis-heterocyclic carbenes, phosphines, amines, imines, arsines, and hybrids, compositions, and derivatives thereof.

In some embodiments of the application, the ligand or metal band has weak or non-nucleophilic stable ions, including but not limited to halogens, borates, sulfonates, and phosphonates.

The ligand may be added to the reaction mixture in the form of a metal complex or as a separate reagent. The ligands, if chiral, may be added as a racemic mixture or as optically pure stereoisomers.

In some embodiments of the application, the carbene is IPr (IPr =1, 3-bis (2, 6-diisopropylphenyl) imidazol-2-subunit; CAS: 244187-81-3).

In some embodiments of the application, the transition metal catalyst is NiCl ₂ DME, or dimers, trimers or higher oligomers thereof, optionally used with NaBArF, wherein NaBArF is used in stoichiometric or catalytic amounts.

In some embodiments of the application, the transition metal catalyst and carbene are used in the form of an isolated complex [ (carbene) NiX ₂ ] L, optionally together with NaBArF, wherein L is a solvent molecule or an isocyanide of formula (II), carbene is IPr (IPr =1, 3-bis (2, 6-di-isopropylphenyl) imidazol-2-ylidene; CAS: 244187-81-3), and X is halogen or other similar group.

In some embodiments of the application, the transition metal catalyst is provided in catalytic amounts in the reaction. In particular embodiments, the catalytic amount is less than 10 mole% relative to an equivalent reagent, which may be a compound of formula (I) or a compound of formula (II), depending on which reagent is in stoichiometric excess.

In some embodiments of the application, the reaction may be carried out with an optional solvent. The solvent is selected from aromatic hydrocarbon, aliphatic hydrocarbon, alicyclic hydrocarbon, halogenated hydrocarbon, alcohol, ether, ester, ketone, nitrile and glycol derivative.

Exemplary aromatic hydrocarbons useful in the present application include, but are not limited to, benzene, toluene, xylenes, and the like. Exemplary aliphatic hydrocarbons useful in the present application include, but are not limited to, pentane, hexane, heptane, octane, and the like. Exemplary alicyclic hydrocarbons useful in the present application include, but are not limited to, cyclohexane, cyclohexanone, methylcyclohexanone, and the like. Exemplary alcohols useful in the present application include, but are not limited to, methanol, ethanol, isopropanol, and the like. Exemplary ethers useful in the present application include, but are not limited to, diethyl ether, methylethyl ether, propyl ether, propylene oxide, and the like. Exemplary esters useful in the present application include, but are not limited to, methyl formate, ethyl formate, butyl formate, pentyl formate, methyl acetate, ethyl acetate, propyl acetate, benzyl benzoate, and the like. Exemplary ketones useful in the present application include, but are not limited to, acetone, methyl butanone, methyl isobutyl ketone, and the like. Exemplary nitriles useful in the present application include, but are not limited to, acetonitrile, propionitrile, acrylonitrile, and the like. Exemplary glycol derivatives useful in the present application include, but are not limited to, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, and the like.

In some embodiments of the application, the solvent is an aromatic hydrocarbon. In some embodiments of the application, the solvent is selected from benzene, toluene, and xylene.

Alternatively, the reaction may be carried out in the absence of a solvent. Ionic liquids such as imidazolium salts can also be used as reaction medium.

In some embodiments of the application, the process may be carried out in an optional buffer to minimize problems associated with isomerization, oligomerization, and polymerization. Examples of buffers useful in the present application include, but are not limited to, ammonium salts, phosphorus buffers, carbonates.

Detailed Description

The reaction is sensitive to oxygen and moisture and the substrate should be dried and degassed (typically overnight on CaH ₂ or CaCl ₂ powder) prior to use. Unless otherwise indicated, all reactions were carried out under an oxygen-free atmosphere of nitrogen or argon, strictly excluding moisture in reagents and glassware. NiBr ₂ DME was purchased from Acros or IL and stored under nitrogen atmosphere and used without further purification. IPr and NaBArF are purchased from Aldrich or Strem. The isonitrile was filtered through a short column of silica gel and dried to remove possible stabilizers before use. The substituted cyclopropenes are prepared according to conventional methods. Toluene was distilled over sodium prior to use.

Analytical Thin Layer Chromatography (TLC) was performed using EM SCIENCE silica gel 60F254 plates. The developed chromatograms were analyzed with ultraviolet lamps (254 nm), phosphomolybdic acid (PMA) or potassium permanganate (KMnO ₄). Liquid chromatography was performed using forced flow (flash chromatography) of the indicated solvent system on silica gel (230-400 mesh). ¹ H and ¹³ C NMR spectra were recorded in CDCl ₃ on a Bruker 400MHz or 300MHz spectrometer. ¹ Chemical shifts in the H NMR spectrum are expressed in ppm on the delta scale as internal standard for residual chloroform (7.27 ppm). The data are reported as chemical shifts, multiplexing (s=singlet, d=double, t=triplet, q=four-wire, m=multi-wire, br=broad), coupling constants in hertz (Hz), and integration. ¹³ Chemical shifts of the C NMR spectrum were reported in ppm on the delta scale from the central peak of CDCl ₃ (77.16 ppm).

In this case, the catalyst of the formula [ (NHC) NiX ₂](NaBArF)_n,[(IPr)NiBr₂]/(NaBArF)₂ as an example can be produced according to, but not limited to, IPr, niBr ₂ DME, and NaBArF in a ratio of 1:1:2 in toluene at 80℃for 3-5 minutes.

The [ (NHC) NiBr ₂]/(NaBArF)₂ catalyst can also be produced by other methods including, but not limited to, mixing a Ni source with 1) an imidazolium salt or ionic liquid, typically with or without a base, or 2) an alkyl, aryl, benzyl, vinyl, alkenyl or alkynyl X, or 3) a typical hydride or hydrogen source, optionally with activators and buffers, including, but not limited to Lewis acid additives, protonic acids and or nucleophiles, or 4) other typical organometallic transformation and manipulation techniques such as hydride addition or elimination steps and substitutions, and the like.

Experimental results indicate that the result of the coupling reaction is very sensitive to the structure of the carbene catalyst, the anti-ion used and the possible preparation method.

General procedure for catalyst formation NHC (0.05 mmol,10 mol%), niBr ₂ DME (0.05 mmol,10 mol%) and NaBArF (0.10 mmol,20 mol%) were added to a baked tube with a stirring bar in a glove box. The catalyst mixture was dissolved in degassed toluene (1 ml) under nitrogen and stirred at 80 ℃ for 3-5 minutes.

General procedure for the synthesis of fused aromatic amines 1 ml of toluene solution of compounds (I) and (II) (0.5 mmol,100mol% and 1mmol,200mol%, respectively) was added to the [ NHC-NiBr ₂](NaBArF)₂ mixture at 80℃and the mixture was stirred overnight (12 hours) and then the mixture was cooled, diluted with n-hexane/ethyl acetate (6 mL, 10:1) and stirred for 30 minutes at room temperature in the open air. The mixture was then filtered through a short column of silica gel and rinsed with 20% ethyl acetate/hexane (50 ml). The solvent was removed under reduced pressure and purified by silica gel chromatography to give the product.

Following the general procedure described above, the following compounds were synthesized from the corresponding starting materials and provided with characterization data.

Example 1

Yield 89%, purification with 5% EA/Hex ¹H NMR(400MHz,CDCl₃)δ:8.17-8.10(m,1H),8.05-7.98(m,1H),7.63-7.52(m,2H),7.35-7.28(m,1H),7.24-7.21(m,2H),7.03(dd,J＝0.8,6.8Hz,1H),6.10(d,J＝7.6Hz,1H),5.61(br,1H),3.14(hept,J＝6.8Hz,2H),2.58(s,3H),1.18(d,J＝6.8Hz,6H),1.09(d,J＝6.8Hz,6H);¹³C NMR(100MHz,CDCl₃)δ:146.9,142.0,136.1,133.4,127.2,126.9,125.8,125.2,124.8,124.1,124.0,120.8,107.2,28.3,24.9,23.3,19.1.

HRMS (EI-MS) calculated C ₂₃H₂₈ N318.2216 (M+H), found 318.2216

Example 2

Yield 81%, purification with 10% EA/Hex

¹H NMR(400MHz,CDCl₃)δ:7.95(d,J＝8.0Hz,1H),7.63(d,J＝8.0Hz,1H),7.44(dt,J＝1.2,8.0Hz,1H),7.37(dt,J＝1.2,7.2Hz,1H),7.35-7.30(m,1H),7.29-7.22(m,2H),6.97(d,J＝8.0Hz,1H),6.04(dd,J＝1.2,8.0Hz,1H),5.70-5.60(br,1H),3.23(hept,J＝6.8Hz,2H),2.48(s,3H),1.20(d,J＝6.8Hz,6H),1.13(d,J＝6.8Hz,6H);¹³C NMR(100MHz,CDCl₃)δ:156.0,155.6,147.0,142.5,135.3,129.1,127.4,125.6,124.7,124.1,122.7,120.5,111.6,111.3,110.3,106.1,28.5,24.8,23.3,14.7.

HRMS (EI-MS) calculated C ₂₅H₂₈ NO:358.2165 (M+H), found 358.2158.

Example 3

95% Yield, purification with 5% EA/Hex

¹H NMR(400MHz,CDCl₃)δ:8.14(dd,J＝1.2,8.4Hz,1H),8.00(dd,J＝1.2,8.4Hz,1H),7.59-7.53(m,1H),7.50-7.40(m,5H),7.38-7.31(m,2H),7.30-7.24(m,2H),7.16-7.12(m,1H),6.24(d,J＝7.6Hz,1H),5.77(br,1H),3.19(hept,J＝6.8Hz,2H),1.21(d,J＝6.8Hz,6H),1.13(d,J＝6.8Hz,6H);¹³C NMR(100MHz,CDCl₃)δ:147.1,143.0,141.5,135.6,132.5,130.6,130.5,128.3,127.9,127.3,127.1,126.7,126.1,125.0,124.2,123.4,120.4,106.9,28.4,25.0,23.4.

HRMS (EI-MS) calculated C ₂₈H₃₀ N380.2373 (M+H), found 380.2376.

Example 4

Yield 60%, purification with 5% EA/Hex

¹H NMR(400MHz,CDCl₃)δ:8.05(dd,J＝1.6,8.4Hz,1H),7.97(dd,J＝1.2,8.0Hz,1H),7.54-7.41(m,7H),7.41-7.35(m,1H),7.27(d,J＝8.0Hz,1H),7.22-7.12(m,2H),7.08-7.02(m,1H)7.00(d,J＝7.6Hz,1H),6.06(br,1H),1.52(s,9H);¹³C NMR(100MHz,CDCl₃)δ:142.2,141.7,141.2,140.9,133.0,132.7,130.4,128.4,127.6,127.2,127.1,127.0,126.9,126.3,126.2,125.5,124.7,123.2,121.3,112.1,35.0,30.8.

HRMS (EI-MS) calculated C ₂₆H₂₆ N352.2060 (M+H), found 352.2058.

Example 5

Yield 28%, purification with 5% EA/Hex

¹H NMR(500MHz,CDCl₃)δ:7.93-7.85(m,2H),7.50-7.40(m,5H),7.41-7.35(m,2H),7.30-7.25(m,1H),7.02-6.95(m,1H),1.51(s,9H);¹³C NMR(125MHz,CDCl₃)δ:141.5,141.2,132.7,130.5,130.1,128.3,127.4,126.9,126.6,125.7,125.4,124.7,120.7,109.4,51.9,30.1;

HRMS (EI-MS) calculated C ₂₀H₂₂ N276.1747 (M+H), found 276.1740.

Example 6

Yield 81%, purification with 5% EA/Hex

¹H NMR(500MHz,CDCl₃)δ:8.20-8.10(m,2H),7.67-7.52(m,2H),7.42-7.36(m,1H),7.35-7.30(m,2H),6.15-6.08(m,1H),5.98-5.82(m,1H),5.72-5.66(m,1H),5.02-4.94(m,1H),4.94-4.84(m,1H),3.45-3.40(m,2H),3.29-3.18(m,2H),2.60-2.55(m,3H),1.25(d,J＝6.8Hz,6H),1.16(d,J＝6.8Hz,6H);¹³C NMR(125MHz,CDCl₃)δ:146.9,141.5,136.9,135.9,135.5,134.0,126.9、126.0、125.0、124.2、124.0、122.9、121.4、120.5、115.1、110.1、39.0,28.3,24.9;23.4,13.9.

HRMS (EI-MS) calculated C ₂₆H₃₂ N358.2529 (M+H), found 358.2521.

Example 7

Yield 62%, purification with 5% EA/Hex

¹H NMR(500MHz,CdCl₃)δ:7.93(dd,J＝1.0,8.5Hz,1H),7.44(dd,J＝7.0,8.5Hz,1H)7.35-7.27(m,2H)7.27-7.23(m,2H),6.94(d,J＝8.0Hz,1H),6.12(d,J＝7.5Hz,1H),5.57(br,1H),3.20-3.08(m,4H),3.00(t,J＝6.5Hz,2H),2.05(hept,J＝6.8Hz,2H),1.18(d,J＝6.8Hz,6H),1.09(d,J＝6Hz,6H).¹³C NMR(125MHz,CDCl₃)δ:130.8,126.9,126.2,124.7,124.4,124.3,123.7,118.2,107.2,31.9,31.0,28.3,24.9,23.5,23.3.

HRMS (EI-MS) calculated C ₂₅H₃₀ N344.2373 (M+H), found 344.2368.

Example 8

Yield 65% purification with 5% EA/Hex

¹H NMR(400MHz,CDCl₃)δ:7.30-7.16(m,3H),6.73(d,J＝8.0Hz,1H),5.92(d,J＝8.4Hz,1H),4.81(br,1H),3.07(hept,J＝6.8Hz,2H),2.65(t,J＝6.4Hz,4H),2.13(s,3H),1.98-1.80(m,4H),1.14(t,J＝6.8Hz,6H),1.13(t,J＝6.8Hz,6H);¹³C NMR(100MHz,CDCl₃)δ:147.1,143.8,136.4,136.0,127.2,126.8,125.5,123.8,121.2,108.7,28.3,27.6,25.0,24.8,23.1,22

HRMS (EI-MS) calculated C ₂₃H₃₂ N322.2529 (M+H), found 322.2520.

All of the above U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications, and non-patent publications mentioned in this specification and/or listed in the application data sheet are incorporated herein by reference, in their entirety.

From the foregoing, it will be appreciated that, although specific embodiments of the application have been described herein, various modifications may be made without departing from the spirit and scope of the application. The application, therefore, is not to be restricted except in the spirit of the appended claims.

Claims

1. A process for reacting a cyclopropene of formula (I) with an isonitrile of formula (II) in the presence of a transition metal catalyst to produce a condensed ring aromatic amine of formula (III), wherein the reaction formula is as follows:

It is characterized in that

Ar ¹ is any one of aryl, heteroaryl and alkenyl,

R ¹ , R ² and R ³ are selected from one of hydrogen, halogen, alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid.

The substituents on the compounds of formula (I) are optionally linked via an alkylene chain.

R ⁴ is optionally one of alkyl, aryl, heteroaryl, alkenyl, alkynyl or metalloid, and is optionally linked to a substituent on the compound of formula (I).

Ar ² is optionally an aryl group, a heteroaryl group (derived from the substituted aryl and heteroaryl groups of Ar ¹ ), or an optionally substituted aliphatic structure (derived from the substituted alkenyl group of Ar ¹ ).

The transition metal catalyst is optionally from Groups 3-12.

The carbene optionally contains any member of a divalent carbon atom.

2. The method according to claim 1, wherein the compound of formula (I) is an optionally substituted cyclopropene, such as 3-methyl-3-phenylcyclopropene, and substituted derivatives thereof.

3. The process according to claim 1, wherein the compound of formula (II) is optionally isonitrile, such as tert-butyl isonitrile, and substituted derivatives thereof.

4. The method according to claim 1, wherein the ligand on the transition metal catalyst is selected from one of carbene, heterocyclic carbene, dicarbene, diheterocyclic carbene, phosphine, amine, imine, arsine and derivatives thereof.

5. The method of claim 1, wherein the catalyst carries a weak or non-nucleophilic stabilizing ion.

6. The method according to claim 1, wherein the transition metal catalyst is generated from [(NHC) _NiBr2 ]L/(NaBArF) ₂ , etc., wherein L is a solvent molecule such as toluene, THF, DME or an isocyanate having formula (II).

7. The method according to claim 1, wherein the method is carried out in a solvent, and the solvent is optionally aromatic hydrocarbons, aliphatic hydrocarbons, alicyclic hydrocarbons, halogenated hydrocarbons, alcohols, ethers, esters, ketones, nitriles and diol derivatives, and ionic liquids such as imidazolium salts.

8. The method of claim 1, wherein the method is performed in a buffer.