WO2011061439A1 - Catalytic phosphination method - Google Patents

Abstract

The invention relates to a double or triple catalytic phosphination method, essentially performed in a single step of injecting phosphine groups on a di-, tri- or tetra-halobiaryl compound.

Description

 CATALYTIC PHOSPHINATION PROCESS

The present invention relates to the field of organic chemistry and more particularly to the field of biaryl compounds, in particular biphenyl and binaphthyl compounds. It relates even more particularly to a process of phosphination catalyzed by a compound based on palladium. The compounds obtained by the new process according to the invention are useful in the chemical industry, especially in the field of the manufacture of catalysts for industrially important reactions such as, for example, asymmetric hydrogenation or the formation of interatomic bonds. in the form of coupling reactions, in particular carbon-carbon, carbon-nitrogen, carbon-oxygen or carbon-phosphorus coupling (for example reactions of Suzuki, Heck, Sonogashira, etc.).

 C-P coupling reactions were less systematically studied than C-C, C-N or C-O coupling reactions. Some catalytic systems have been developed to date, but most of them only allow monophosphination of phenyl derivatives.

 The double (and a fortiori triple) phosphination is rarely described and only concerns the synthesis of diphosphine ligands derived from biphenyl and binaphthyl groups starting from bis-triflate substrates (BINAP). However, the substrates derived from biphenyl and binaphthyl groups show completely different reaction profiles. In general, synthesis methods described in the literature based on bis-triflate compounds require at least 3 days of reaction heating to obtain good yields starting from phenolic compounds.

 Thus, EP 135392 discloses a process for the preparation of 2,2'-bis (diphenylphosphino) -1'-binaphthyl (BINAP) comprising in particular the reaction of binaphthol with triphneylphosphine dibromide at a temperature of 320 ° C. These very harsh conditions as well as the implementation of a toxic product greatly limit the use of this process.

US Patent No. 5,399,771 discloses a process for preparing BINAP from 2,2'-di (trifluoromethanesulfonyl) -1,1-baphthyl in only two steps and with good yield but lasts about three days. US Patents 5902904 and EPI 047669 describe processes which make it possible to obtain in two stages large amounts of BINAP with yields that are, however, lower than those of the process described in US Pat. No. 5,399,771.

 Biphenyl ligands such as 2,2'-dimethyl-6,6'-bis (diphenylphosphino) diphenyl (BIPHEMP) and its analogs were the first examples of optically active bis (triarylphosphines) containing an atropisomeric axis. Subsequently many ligands of this category have been synthesized and patented.

 In 1991, Schmid developed a process involving a step of ortho-lithiation / iodination of 3- (methoxyphenyl) diphenylphosphine oxide followed by Ullman coupling between two identical phenyl moieties leading to bis (diphenylphosphino) biphenyl oxides. racemic (Schmid R. et al Helv Chim Acta 1991, 74, 370). Another approach is based on the synthesis of ortho, ortho'-dibromobiphenyl which after a double bromine / lithium exchange is trapped with two equivalents of chlorodiphenylphosphine which allows the synthesis of the diphosphine. (BIPHEMP: Schmid R. et al Helv Chim Acta 1988, 71, 897). However, this approach is not applicable to congested biphenyls because of the formation of phosphafluorenes (1H-benzo [b] phosphindole).

 In the application WO 2006/002730, the inventors describe a method for preparing substituted biaryldiphosphine ligands from 2,2 ', 6,6'-tetrabromobiphenyl comprising several steps of metal-substitution exchange reactions, the subtituents being essentially alkyl derivatives or arylphosphines.

 Murata M. et al. (Tetrahedron (2004), 60, 7397-7403) describe a process for the formation of CP bonds between halogenated aryls and secondary phosphines which employs a catalyst system based on palladium and an additional ligand (diPPF diisopropylphosphinoferrocene). essential for catalytic activity. Despite the presence of this catalytic system, it takes about twenty hours to obtain industrially acceptable yields.

Thus, there is a real need for efficient double or triple phosphination processes for dihalobiaryl compounds, namely which make it possible to obtain biarylphosphine ligands in good yields, without the additional use of generally expensive ligands, with little or no formation of phosphafluorene and with durations compatible with industrial use.

 The present invention aims to overcome at least some of the aforementioned drawbacks.

 Indeed, the inventors have developed a process for double or triple catalytic phosphination of dihalobiaryls to obtain large amounts of diarylphosphines desired in less than 5 hours, thus giving access to a wide variety of families of ligands.

 Thus, the subject of the present invention is a process for double or triple catalytic phosphination, essentially carried out in a single step of introducing phosphine groups onto a di, tri or tetrahalobiaryl compound, characterized in that it essentially consists of :

 contacting said di, tri or tetrahalobiaryl compound with at least one molar equivalent of phosphine group per halogen atom to be substituted in said halogenated compound, preferably with a molar excess of at least 10%,

 in the presence of an effective amount of a Pd-based catalyst and a base and in the absence of any additional ligand,

 - all in a solvent at a temperature of at least 100 ° C,

 said di, tri or tetrahalobiaryl compound used being chosen from the group formed by the di, tri or tetrahalobiphenyls of the respective formulas I, II or III and the dihalobinaphthyls of the formula IV below:

dans laquelle

in which

R ¹ represents Br or I,

R ² represents Br or I, and R ³ is H, F, Cl, Br, I, Z, OZ, NR'R ", an aryl group or a substituted aryl group or polysubstituted, Z represents a saturated linear or branched alkyl group in Ci to C _6, optionally substituted , an optionally substituted C ₃ to C ₁₀ saturated cycloalkyl group, a saturated C ₁ to C ₆ perfluoroalkyl group,

R 'and R "being independently selected from the group consisting of a hydrogen atom, a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, a saturated cycloalkyl group, C ₃ -C, optionally substituted,

R ⁴ representing H, Cl or Br,

wherein R ¹ , R ² and R ⁴ have the meanings given for formula I, and wherein the substituent R ³ is selected from the group consisting of saturated chains:

(CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

wherein R ¹ and R ² have the meanings given for formula I, and wherein the substituents R ³ and R ⁴ are independently selected from the group consisting of saturated chains: (CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

in which R ¹ , R ² and R ³ have the meanings given for formula I and R ⁵ , identical or different from R ³ , has the same definitions as R ³ .

 For the purposes of the present invention, the term "additional ligand" means ligands such as, for example, DPPF (1,2-bis-diphenylphosphinoferrocene), DPEphos (bis (2-diphenylphosphinophenyl) ether), DiPPF (1,4-bis (diisopropylphosphino) ) ferrocene)., Biphenyl (S-phos, Brettphos, Ruphos, Dave phos and other Buchwald), all ferrocenes (Togni, careterro ..), Nolan carbene, dienes, phosphine free (BOX).

Within the meaning of the present invention, linear saturated alkyl means or branched Ci to C _6, especially a group selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n- pentyl, isopentyl and n-hexyl.

For the purposes of the present invention, the term "saturated C ₃ -C ₁₀ cycloalkyl group" is intended especially to mean a group chosen from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl.

For the purposes of the present invention, the term "saturated Ci-C ₆ perfluoroalkyl group" means a group in which all the hydrogen atoms are replaced by a fluorine atom, in particular a CF ₃ or C ₂ F _{5 group} .

 For the purposes of the present invention, the term "aryl group" means a group comprising at least one aromatic ring and comprising 6 to 20 carbon atoms, preferably 6 to 10 carbon atoms. By way of example, mention may be made of phenyl and naphthyl groups.

Preferably, the process according to the invention is characterized in that said di, tri or tetrahalobiaryl compound used is chosen from the group formed by: a) di, tri or tetrahalobiphenyl compounds of formula I wherein: R ¹ represents Br or I,

R ² represents Br or I, and

R ³ represents H, F, Cl, Br, I, CH ₃ , OCH ₃ , N (CH ₃ ) ₂ , OCF ₃ , or Ph,

R ⁴ representing H,

 or

R ⁴ representing Cl when R ³ = C1, R ^{1 =} Br and R ² = I or,

R ⁴ represents Br when R ³ = H ₃ CO and R ^{1 =} R ² = I, b) the di, tri or tetrahalobiphenyl compounds of formula II in which: R ¹ , R ² and R ⁴ have the meanings given for the formula I, and

R ³ is selected from the group consisting of saturated chains O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O, c) di, tri or tetrahalobiphenyl compounds of formula III in which :

R ¹ and R ² have the meanings given for formula I, and

R ³ and R ⁴ are independently selected from the group consisting of saturated O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O chains.

According to another advantageous characteristic, an optionally substituted di, tri or tetrahalobiaryl compound is used, which contains a single iodine atom per molecule.

Advantageously, at least one of R ¹ , R ² and R ³ is an iodine atom. This is called mono, di, tri or tetraiodoaryl compounds depending on the number of iodine atoms present.

More preferably, the process according to the invention is characterized in that a di, tri or tetrahalobiaryl compound of formula I, II, III or IV is used in which R ^{1 =} R ² '

Even more preferably, said formula I, II, III or IV of the di, tri or tetrahalobiaryl compound satisfies R ^{1 =} R ² = I.

The di or tetrahalobiaryl compound used in the process according to the invention may be a symmetrical compound, that is to say of formula I, III or IV in which R ^{1 =} R ² and which also satisfies R ³ = R ⁴ or R ³ = R ⁴ when these pairs of groups are present, according to the formula in question or an asymmetric compound. According to another advantageous characteristic, provides the necessary phosphine groups by means of a compound of formula HP (R '") ₂ wherein R"' is a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, saturated C ₅ to C ₁₀ saturated cycloalkyl group, optionally substituted, an aryl group, optionally substituted by one or more substituents selected from the group consisting of a halogen, a nitro, amino, saturated linear or branched C1 to C ₆ alkyl, alkoxy group; saturated linear or branched Ci -C ₆ dialkylamino or saturated linear or branched Ci to C ₆ R '"is preferably Ph or cyclohexyl.

As regards the catalyst used in the process according to the invention, the base may be any base known to those skilled in the art; it can be chosen in particular from the group comprising potassium acetate (KOAc), potassium phosphate (K ₃ PO ₄ ), cesium flurour (CsF) and potassium carbonate (K ₂ CO ₃ ). The palladium catalyst may be any catalyst known to those skilled in the art; it may especially be chosen from the group comprising palladium (O) complexes, such as tris (dibenzylideneacetone) dipalladium (0) (Pd ₂ (dba) ₃ ) or palladium II [(Pd (II)], such as acetate of palladium (Pd (OAc) ₂ ).

Advantageously, the catalyst consists of a mixture of Pd (OAc) ₂ and KOAc; more preferably the catalyst content is at least 2 mol% relative to the reaction mixture and a KOAc content of at least 2 molar equivalents.

The solvent used may be any solvent known to those skilled in the art. Advantageously, it is chosen from the group comprising dimethylformamide (DMF), toluene, N, N-dimethylacetamide (DMA) and mixtures comprising at least two of these different solvents; advantageously the solvent essentially comprises at least one compound having at least one dimethylamide group (CH ₃ ) ₂ NC (O) -.

 According to another important characteristic, the solvent used consists essentially of DMA (N, N-dimethylacetamide), that is to say at least 99% by mass of pure DMA.

Advantageously, the process according to the invention is further characterized in that the reaction temperature is chosen to be between 120 ° C and 150 ° C measured at atmospheric pressure. When the solvent is DMA, the temperature is advantageously 130 ° C. Furthermore, the process according to the invention is also characterized in that the reaction time is chosen to be between 30 minutes and 3 hours, preferably equal to 2 hours.

 The process according to the invention makes it possible for the first time to efficiently obtain the desired di or triphosphine products within a few hours instead of a few days. It also allows direct, rapid and economical access to new compounds by avoiding or generally reducing the formation of unwanted by-products, such as in particular phosphafluorenes (1-phenyl-1H-dibenzo [b] phosphindoles) or mono-coupling.

 The present invention also provides for the use of new halogenated compounds as synthesis intermediates.

 The present invention therefore also relates to di, tri or tetrahalobiaryl compounds for the implementation of the method according to the invention, that is to say the use of said compounds, said compounds being characterized in that they are chosen from the group formed by the di, tri or tetrahalobiphenyls of the respective formulas I, II or III and the dihalobinaphthyls of the formula IV below:

dans laquelle

in which

R ¹ represents Br or I,

R ² represents Br or I, and

R ³ represents Η, F, Cl, Br, I, Z, OZ, NR'R ", Ph or substituted Ph group or polysubstituted, Z represents a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, an optionally substituted C ₃ to C ₁₀ saturated cycloalkyl group, a saturated C 1 to C ₆ perfluoroalkyl group,

R 'and R "being independently selected from the group consisting of a linear saturated alkyl or branched C l -C _6, optionally substituted cycloalkyl saturated C ₃ to Cio, optionally substituted, R ⁴ representing H, Cl or Br,

wherein R ¹ , R ² and R ⁴ have the meanings given for formula I, and wherein the substituent R ³ is selected from the group consisting of saturated chains:

(CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

wherein R ¹ and R ² have the meanings given for formula I, and wherein the substituents R ³ and R ⁴ are independently selected from the group consisting of saturated chains:

(CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

dans laquelle R¹ , R² et R³ ont les significations données pour la formule I et R⁵ identique ou différent de R³ a les mêmes définitions que R³.

in which R ¹ , R ² and R ³ have the meanings given for formula I and R ⁵ identical to or different from R ³ has the same definitions as R ³ .

 Advantageously, the di, tri or tetrahalobiaryl intermediate compound according to the invention is characterized in that it is chosen from the group formed by: a) compounds of formula I in which:

R ¹ represents Br or I,

R ² represents Br or I, and

R ³ represents H, F, Cl, Br, I, CH ₃ , OCH ₃ , N (CH ₃ ) ₂ , OCF ₃ , or Ph,

R ⁴ representing H,

 or

R ⁴ representing Cl when R ³ = C1, R ^{1 =} Br and R ² = I or,

R ⁴ representing Br when R ³ = H ₃ CO and R ^{1 =} R ² = I, b) compounds of formula II in which:

R ¹ , R ² and R ⁴ have the meanings given for formula I, and

R ³ is selected from the group consisting of saturated chains O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O, c) compounds of formula III in which:

R ¹ and R ² have the meanings given for formula I, and

R ³ and R ⁴ are independently selected from the group consisting of saturated O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O chains. Preferably, the di, tri or tetrahalobiaryl compound according to the invention is characterized in that it contains only one iodine atom per molecule.

Furthermore, the di, tri or tetrahalobiaryl compound according to the invention is further characterized in that its formula I, II, III or IV satisfies R ^{1 =} R ² , preferably R ^{1 =} R ² = I.

Preferably, the di or tetrahalobiaryl compound according to the invention is characterized in that its formula I or III further satisfies R ³ = R ⁴ or R ^{3 '} = R ^4' .

The subject of the present invention is also the di or triphosphine biaryl compounds which can be obtained by carrying out the process according to the invention, of formula I, II, III or IV, except for the compounds of formula I in which:

R ¹ = R ² = PPh ₂ and R ³ = H, CH ₃ or OCH ₃ and R ⁴ = H;

 * of formula II in which:

R ¹ = R ² = PPh ₂ and R ^{3 '} = (CH ₂ ) ₄ and R ⁴ = H,

 * of formula III in which:

R ¹ = R ² = PPh ₂ and R ^{3 '} = R ^4' = O-CH ₂ -O or O- (CH ₂ ) ₂ -O or O-CF ₂ -O,

of formula IV in which R ^{1 =} R ² = PPh ₂ ,

Advantageously, the bi or triphosphine compounds according to the invention are characterized in that their formula I or III satisfies R ^{1 =} R ² and simultaneously R ³ = R ⁴ or R ^{3 '} = R ^4' .

More preferably, the compounds according to the invention are further characterized in that all the phosphine groups present are -PPh ₂ groups.

 The compounds of the present invention are particularly interesting for the industry in the context of the creation of kits or kits of ligands for research, for their use in catalysis processes (manufacture of pharmaceutical products, agrochemicals, in the field of perfumery ...)

The subject of the present invention is therefore also the use of a di or triphosphine compound according to the invention as a ligand for the formation, with one or more metals having a catalytic activity, of a catalytic complex, in particular for asymmetric hydrogenation. and forming interatomic bonds, in particular CC, CN, C-O and CP couplings, said compounds being in particular chosen from the group comprising:

 (6- (fluoro) biphenyl-2,2'-diyl) bis (diphenylphosphine)

 - (6-chlorobiphenyl-2,2'-diyl) bis (diphenylphosphine)

 (6-Methyl-biphenyl-2,2'-diyl) bis (diphenylphosphine)

 2 ', 6'-bis (diphenylphosphino) -N, N-dimethylbiphenyl-2-amine

 (6- (trifluoromethoxy) biphenyl-2,2'-diyl) bisdiphénylphosphine

2,2'-bisdiphenylphosphino-6-phénylbiphényle

 2- (5- (diphenylphosphino) benzo [(1) [1,3] dioxol-4-yl) phenyl)

 diphenylphosphine

(2- (5- (Diphenylphosphino) -2,2-difluorobenzo [d] [1,3] dioxol-4-yl) phenyl) diphenyl phosphine (2- (6- (diphenylphosphino) -2,2,3,3-tetrafluoro-2,3-dihydrobenzo

 [δ] [1,4] dioxin-5-yl) phenyl) diphenylphosphine

 6'-methoxybiphenyl-2,2 ', 6-triyl) tris (diphenylphosphine)

The invention will be better understood, thanks to the following description, which relates to preferred embodiments, given by way of non-limiting examples.

 The present invention therefore relates to a double or triple catalytic phosphination process, essentially carried out in a single step of introducing phosphine groups onto a di or trihalobiaryl compound, characterized in that it consists essentially of:

 contacting said di or trihalobiaryl compound with at least one molar equivalent of phosphine groups per halogen atom to be substituted on said halogenated compound, preferably with a molar excess of at least 10%,

 in the presence of an effective amount of a Pd-based catalyst and a base and in the absence of any additional ligand,

 - all in a solvent at a temperature of at least 100 ° C,

 said di or trihalobiaryl compound used being chosen from the group formed by the di or trihalobiphenyls of the respective formulas I or II and the dihalobinaphthyls of the formula III or IV mentioned above.

 The terms "substituted" and "polysubstituted" used above in said formulas mean that the base group in question may in turn be grafted with one or more other chemical groups (substitution), the number of carbon atoms. indicated being that of each basic group (eg alkyl) and therefore does not include the number of carbon atoms due to the additional substituent (s). Preferred substituents for the acyclic chains are independently selected from the following groups: alkyl, alkoxy, alkylthio, aryl, monoalkylamino or dialkylamino where

 - Alkyl in turn means a saturated hydrocarbon chain, linear or branched containing 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, more preferably 1 to 8 carbon atoms. By way of example, mention may be made of the groups mentioned above, in particular the methyl group.

alkoxy, alkylthio, monoalkylamino or dialkylamino denote an alkyl-oxy, alkyl-thio, alkyl-amino or dialkylamino group whose saturated linear or branched alkyl chains each contain from 1 to 8 carbon atoms, and

 aryl denotes a group comprising at least one aromatic nucleus and comprising 6 to 20 carbon atoms, preferably 6 to 10 carbon atoms. By way of example, mention may be made of phenyl and naphthyl groups.

 For the purposes of the present invention, the term "perfluoroalkyl" denotes a linear or branched saturated hydrocarbon alkyl chain containing 1 to 6 carbon atoms and in which all the hydrogen atoms have been replaced by fluorine.

According to a first aspect, the process according to the invention is characterized in that the required phosphine groups are provided by means of a compound of formula HP (R "') ₂ in which R"' is a linear saturated alkyl group or branched Ci to C _6, optionally substituted cycloalkyl saturated C ₅ -C, optionally substituted aryl, optionally substituted by one or more substituents selected from the group consisting of halogen, nitro, amino, linear saturated alkyl or branched -C ₆ alkoxy linear or branched saturated C l -C _6, or dialkylamino saturated linear or branched Ci to C ₆ R '"is preferably Ph or a cyclohexane group. the way the more preferred, therefore uses HPPh ₂ commercially available.

The catalysts which are suitable for carrying out the process according to the invention are based on Pd (O) or Pd (II). Preferably, a catalyst consisting of a mixture of Pd (OAc) ₂ and KOAc, with a catalyst content of at least 2 mol% relative to the reaction mixture and a KOAc content of at least 2 molar equivalents.

 Advantageously, a liquid reaction solvent consisting mainly (at least predominantly by weight) of a compound having at least one dimethylamide group, preferably a liquid solvent essentially consisting of DMA (N, N-dimethylacetamide), is used. that is at least 99% by mass of pure DMA.

 Optimally, to ensure a good yield under economically profitable conditions, the reaction temperature is chosen to be between 120 ° C and 150 ° C measured at atmospheric pressure.

Advantageously, compared with analogous methods of the state of the art, the reaction time is chosen to be between 30 minutes and 3 hours, preferably equal to 2 hours, which is a significant reduction compared to known methods. The di, tri, or tetrahalobiaryl compounds used by the process according to the invention are either commercially available or can be synthesized by those skilled in the art by known techniques or described in the literature starting from commercially available molecules.

 In particular, the di, tri or tetrahalobiaryl compounds for carrying out the process according to the invention are chosen from the group formed by di, tri or tetrahalobiphenyl of the respective formulas I, II or III and the dihalobinaphthyls of the formula IV below:

dans laquelle R¹ représente Br ou I,

in which R ¹ represents Br or I,

R ² represents Br or I, and

R ³ is H, F, Cl, Br, I, Z, OZ, NR'R ", Ph or substituted Ph group or polysubstituted, Z represents a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, an optionally substituted C ₃ to C ₁₀ saturated cycloalkyl group, a saturated C 1 to C ₆ perfluoroalkyl group,

R 'and R "being independently selected from the group consisting of a linear saturated alkyl or branched C l -C _6, optionally substituted cycloalkyl saturated C ₃ to Cio, optionally substituted,

R ⁴ representing H, Cl or Br,

dans laquelle R¹, R² et R⁴ ont les significations données pour la formule I, et dans laquelle le substituant R³ est choisi dans le groupe formé par les chaînes saturées:

wherein R ¹ , R ² and R ⁴ have the meanings given for formula I, and wherein the substituent R ³ is selected from the group consisting of saturated chains:

(CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

wherein R ¹ and R ² have the meanings given for formula I, and wherein the substituents R ³ and R ⁴ are independently selected from the group consisting of saturated chains:

(CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

dans laquelle R¹, R² et R³ ont les significations données pour la formule I et R⁵, identique ou différent de R³, a les mêmes définitions que R³.

in which R ¹ , R ² and R ³ have the meanings given for formula I and R ⁵ , identical or different from R ³ , has the same definitions as R ³ .

dans laquelle R³ représente H, F, Cl, Br, I, Z, OZ, NR'R", phényle (Ph), ou un groupement Ph substitué ou polysubstitué, Z représentant un groupement alkyle saturé linéaire ou ramifié en Ci à C₆, éventuellement substitué, un groupement cycloalkyle saturé en C₃ à Cio, éventuellement substitué, un groupement perfluoroalkyle saturé en Ci à C₆, The biaryl diphosphine compounds having the formula (la)

in which R ³ represents H, F, Cl, Br, I, Z, OZ, NR'R ", phenyl (Ph), or a substituted or polysubstituted Ph group, Z representing a linear or branched C1 to C saturated alkyl group; ₆ , optionally substituted, an optionally substituted C ₃ to C ₁₀ saturated cycloalkyl group, a saturated C ₁ to C ₆ perfluoroalkyl group,

R 'and R "being independently selected from the group consisting of a hydrogen atom, a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, a saturated cycloalkyl group, C ₃ -C, optionally substituted,

R ⁴ representing H, Cl or Br,

provided that R ³ and R ⁴ are not simultaneously H, that if R ³ is H then R ⁴ is not Cl, that if R ³ is Z or OZ then R ⁴ is not H,

are new and part of the invention:

 Compounds of formula (IIa)

a)

at)

wherein R ⁴ has the meanings given for formula Ia and R ³ is selected from the group consisting of saturated chains:

(CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive), provided that if R ⁴ is H then R ³ is not - (CH ₂ ) ₄ - are new and are part of of the invention:

The compounds of formula (IIIa)

dans laquelle R³ et R⁴ sont choisis dans le groupe formé par les chaînes saturées:

wherein R ³ and R ⁴ are selected from the group consisting of saturated chains:

(CH ₂ ) _n , n being an integer from 3 to 6 (inclusive),

0- (CH ₂ ) _m -0, m being an integer between 1 and 4 (inclusive),

0- (CF ₂ ) _p -0, p being an integer between 1 and 4 (inclusive), are new and form part of the invention.

 The compounds of formula (IVa)

dans laquelle R³ et R⁵, identiques ou différents représentent chacun H, F, Cl, Br, I, Z, OZ, NR'R", phényle (Ph), ou un groupement Ph substitué ou polysubstitué, Z représentant un groupement alkyle saturé linéaire ou ramifié en Ci à C₆, éventuellement substitué, un groupement cycloalkyle saturé en C₃ à C₁₀, éventuellement substitué, un groupement perfluoroalkyle saturé en Ci à C₆,

in which R ³ and R ⁵ , which are identical or different, each represent H, F, Cl, Br, I, Z, OZ, NR'R ", phenyl (Ph), or a substituted or polysubstituted Ph group, Z representing an alkyl group saturated linear or branched C l -C _6, optionally substituted cycloalkyl saturated C ₃ -C _10, optionally substituted, saturated perfluoroalkyl group to C _6,

R 'and R "being independently selected from the group consisting of a hydrogen atom, a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, a saturated cycloalkyl group, C ₃ -C _10, optionally substituted,

provided that R ³ and R ⁵ are not simultaneously H or OCH ₃

are new and part of the invention.

 FIG. 1 illustrates the weak formation of phosphafluorene during the synthesis of biphosphine compounds according to the process of the invention.

Figure 2 illustrates the synthesis of triphosphine compounds according to the process of the invention from mono and diiodinated compounds. Figure 3 illustrates the synthesis of biphosphine compounds according to the method of the invention.

 Examples of syntheses of compounds having a general formula of type I:

As an indication, non-limiting examples of syntheses of starting compounds used in the process of the invention will be given below.

General method of synthesis of dibromobiaryls or bromoiodobiaryls:

Conditions a:

 At -78 ° C, butyllithium (2 eq) in hexane was added dropwise to a substrate solution (1 eq) in THF (20.0 ml per 20 mmol of substrate). After 1 h, 1,2-dibromobenzene or 1-bromo-2-iodobenzene (1 eq) was added dropwise and the reaction mixture was allowed to reach 25 ° C. After 15 h, distilled water was added followed by extraction with ethylacetate. The combined organic phases were dried, filtered and evaporated. Conditions b:

 At -100 ° C, tert-butyllithium (2 eq) in pentane was added dropwise for 3 h to a solution of the substrate (1 eq) in THF (210 ml for 50 mmol of substrate). After 1 h at -78 ° C, 1, 2-dibromobenzene or 1-bromo-2-iodobenzene (1 eq) was added dropwise and the reaction mixture was allowed to reach 25 ° C in the air. 12 hours. Distilled water was added followed by ethyl acetate extraction. The combined organic phases were dried, filtered and evaporated.

Conditions c:

At -78 ° C the substrate (1 eq) was added to a solution of sec-butyllithium (1 eq.) In cyclohexane and THF (35 mL per 25 mmol of substrate). After 45 min, 1, 2-dibromobenzene (1 eq) was added and the mixture was allowed to reach room temperature within 12 h. Water was added followed by ethyl acetate extraction. The combined organic phases were dried, filtered and evaporated. Conditions of:

 At -78 ° C, tert-butyllithium (2 eq) in pentane was added dropwise to a substrate solution (1 eq) in THF. (20.0 ml per 20 mmol of substrate) for 2 h. After 1 h, 1,2-dibromobenzene (1 eq) was added dropwise and the reaction mixture was allowed to reach 25 ° C. Distilled water was added followed by ethyl acetate extraction. The layered organic phases were dried, filtered and evaporated.

Example 1 Synthesis of 2,2'-dibromo-6-fluorobiphenyl

Synthesized under the above conditions a) starting from 1-bromo-3-fluoro-2-iodobenzene. Chromatography on silica gel with 19: 1 ethylacetate / cyclohexane gave 2,2'-dibromo-6-fluorobiphenyl (52%) as a colorless powder with a melting point of 61-63 ° C. .

1 H NMR (CDCl ₃ , 400 MHz): δ = 7.70 (dd, J = 8.0, 1, 2 Hz, 1H), 7.48 (td, J = 7.9, 1.0 Hz, 1H), 7.40 (dt, J = 7.8, 1.3 Hz, 1H), 7.30 (m, 3H), 7.13 (dt, J = 8.6, 1.1). Hz, 1H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 159.9 (d, J = 255.3 Hz), 136, 1, 132,7, 131, 4, 130.5, 130.3, 130, 1 , 128.3 (d, J = 3.5 Hz), 127.3, 124.7 (d, J)

= 3.2 Hz), 124.0, 1 14.7 (d, J = 22.6).

¹⁹ F NMR (CDCl ₃ , 376 MHz): δ = -109, 1 (dd, J = 8.9, 6.5 Hz). MS (Cl): m / z (%) = 330 (87) [M ⁺ ], 312 (26), 251 (100), 170 (99). Ci ₂ H ₇ Br ₂ F (329.99):% calculated C 43.68, H 2, 14; found C 44.00, H 2, 10,

Example 2 Synthesis of 2-bromo-6-fluoro-2'-iodobiphenyl

Synthesized under the conditions a) above from 1-bromo-3-fluoro-2-iodobenzene. Crystallization from methanol gave 2-bromo-6-fluoro-2'-iodobiphenyl (80%) as a colorless powder with a melting point of 86-88 ° C.

1 H NMR (300 MHz, CDCl ₃ ): δ = 7.89 (dd, J = 7.9, 1.1 Hz, 1H), 7.42 (dt, J = 8.0, 0.9 Hz, 1H), 7.36 (dd, J = 7.5, 1.2 Hz, 1H), 7.20 (dd, J = 8.3, 2.4 Hz, 1H), 7.15 (dd, J = 7.8, 1.8 Hz, 1H), 7.06 (m, 2H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 159.9 (d, J = 249.7 Hz), 140.5, 139.0, 130.5, 130.4, 130.0, 128.3 , 128.3, 128.2, 124.8 (d, J = 3.2 Hz), 114.8 (d, J = 22.5 Hz), 99.7,

Ci ₂ H ₇ BrIF (376.99):% calculated C 38.23, H 1.87; found C 38.22,

H, 2.06,

MS (EI): m / z (%) = 378 (41) [M ⁺ ], 297 (52) [M ⁺ -Br], 249 (26) [M ⁺ -I], 170 (100) [M ^+] - Br - I].

Example 3 Synthesis of 2,2 ', 6-Tribromobiphenyl

Synthesized under conditions b) starting from 1,3-dibromo-2-iodobenzene. Purification by flash chromatography gave 2,2 ', 6-tribromobiphenyl (97%) as a colorless powder with a melting point of 95-97 ° C.

1 H NMR (400 MHz, CDCl ₃ ): δ = 7.69 (d, J = 8.1 Hz, 1H), 7.64 (dd, J = 8.1, 0.7 Hz, 2H), 7.42 (tt, J = 7.5, 0.9 Hz, 1H), 7.29 (ddt, J = 7.8, 1.8, 0.7 Hz, 1H), 7.18 ( dd, J = 7.6, 1.6 Hz, 1H), 7.12 (dd, J = 8.1, 0.7 Hz,

1H).

¹³ C NMR (101 MHz, CDC1 _3): δ = 142.2, 141.9, 132.6, 131.4, 130.6, 130.3, 129.8, 127.4, 124.4, 123 , 3

Ci ₂ H ₇ Br ₃ (390.7):% calculated C 36.87, H 1.81; found C 36.82, H 1.66,

Example 4 Synthesis of 2,6-dibromo-2'-iodobiphenyl

Synthesized under the conditions b) above from 1,3-dibromo-2-iodobenzene. Purification by flash chromatography gave 2,6-dibromo-2'-iodobiphenyl (71%) as a colorless powder with a melting point of 100-102 ° C.

1 H NMR (400 MHz, CDCl ₃ ): δ = 7.89 (dd, J 7.9, 1.0 Hz, 1H), 7.57 (d, J 8 Hz, 2H), 7.39 ( td, J 7.6, 1, 2 Hz, 1H), 7.00 (m, 3H). ¹³ C NMR (101 MHz, CDC1 _3): δ = 146.0, 144.9, 139.0 (2 C), 131.8 (2 C), 130.5, 129.8, 129.7, 128 , 4, 124.7, 99.2,

Example 5 Synthesis of 2,2'-dibromo-6-chlorobiphenyl

Synthesized under conditions b) starting from 1-bromo-3-chloro-2-iodobenzene. The dark brown oil was purified by silica gel filtration with cyclohexane as eluent to give 2,2'-dibromo-6-chorobiphenyl (91%) as a white solid with a melting point of 55.degree. - 57 ° C.

1 H NMR (CDCl ₃ , 300 MHz): δ = 7.63 (dd, J = 8.0, 1.1 Hz, 1H), 7.53 (dd, J = 8.1, 1.1 Hz, 1H), 7.4-7.3 (m, 2H), 7.23 (td, J = 7.9, 1.8Hz, 1H), 7.2-7.1 (m, 2H); H).

1 ³ C NMR (75 MHz, CDC1 _3): δ = 140.6, 140.1, 134.9, 132.7, 131.1,

130.8, 130.0, 129.9, 128.5, 127.5, 124.9, 123.6,

Example 6 Synthesis of 2,2'-dibromo-6-trifluoromethoxybiphenyl Synthesized under the conditions d) above where 1-bromo-2-iodo-3-trifluoromethoxyanisole was added to a solution of tert-butyllithium in pentane and THF. After 5 min, the temperature was raised to -78 ° C for 15 min. After usual treatment, chromatography on silica gel using cyclohexane as eluent followed by crystallization in ethanol gave 2,2'-dibromo-6-trifluoromethoxybiphenyl (58%) as colorless needles having one point. m.p. 68-70 ° C.

1 H NMR (300 MHz, CDCl ₃ ): δ = 7.65 (dd, J = 8.0, 1.1 Hz, 1H), 7.59 (dd, J = 9.1, 1.6 Hz, 1H), 7.35 (td, J = 7.5, 1.3 Hz, 1H), 7.3-7.1 (m, 4H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 147.5 (d, J = 1, 5 Hz), 137.1, 135.7, 132.7, 131.1, 131.0, 130.3 , 130.1, 127.4, 125.6, 123.9, 120.4 (q, J = 258.9 Hz), 119.4 (d, J = 1.7 Hz).

MS (EI): m / z (%) = 395.9 (75) [M ⁺ ], 315.0 (70) [M ⁺ -Br], 248.0 (66) [M ⁺ -Br-CF ₃ ], 236.1 (45) [M ⁺ - 2 Br]. Example 7 Synthesis of 2,2'-dibromo-6-methylbiphenyl

At -78 ° C, butyllithium (16.3 mmol, 1 eq) in hexane (10.6 ml) was added dropwise to a solution of 2,2 ', 6-tribromobiphenyl (6.36 g). g, 16.3 mmol, 1 eq.) in THF (33.0 ml). The aryllithium intermediate compound was trapped with iodomethane. After usual treatment, silica gel chromatography gave 2,2'-dibromo-6-methylbiphenyl (96%). M.p. 54-56 ° C.

1 H NMR (CDCl ₃ , 300 MHz): δ = 7.80 (dd, J = 8.0 Hz, 1.1 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H) , 7.53 (td, J = 7.5, 1.2 Hz, 1H), 7.22-7.42 (m, 4H), 2.19 (s, 3H).

¹³ C NMR (CDCl3, 75 MHz): δ = 132.7, 130.7, 123.0, 129.3, 129.2, 128.8, 127.6, 21.0,

CisHio Br ₂ (326.03):% calculated C 47.89, H 3.09; Found% C 48.01, H 3.14,

Example 8: Synthesis of 2,2'-dibromo-6-iodobiphenyl A-78 ° C, butyllithium (16.3 mmol, 1 eq) in hexane (10.6 ml) was added dropwise to a solution of 2,2 ', 6-tribromobiphenyl (6.36 g, 16.3 mmol, 1 eq) in THF (33.0 mL). The aryllithium intermediate was trapped with iodine in THF. After usual treatment, silica gel chromatography gave 2,2'-dibromo-6-iodobiphenyl (36.1 g, 83.2 mmol, 83%). Melting point 100-103 ° C.

1H NMR (CDCl3, 300MHz): δ = 7.83 (td, J = 8.2, 1.1 Hz, 1H), 7.61 (td, J = 7.5, 1.2 Hz, 2H), 7.19-7.35 (m, 2H), 7.08 (dd, J = 7.51, 1.66 Hz, 1H), 6.86 (t, J = 8.0 Hz, 1H),

¹³ C NMR (CDCl3, 75 MHz): δ = 145.7, 145.2, 138.1, 132.8, 132.6, 130.7, 130.6, 129.9, 127.6, 123, 4, 123.1, 100.1,

Ci ₂ H ₇ Br ₂ I (437.90):% calculated C 32.91, H 1.61; found C 33.03,

H, 1.72, Example 9 Synthesis of 2,2'-dibromo-6-methoxybiphenyl

1) At -78 ° C, butyllithium (45.5 mmol, 1 eq) in hexane (30.0 ml) was added to a solution of 2,2 ', 6-tribromobiphenyl (17.8 g). 45.5 mmol, 1 eq.) In THF (95.0 mL). Immediately after the completion of the addition, fluorodimethoxyborane diethyl ether (10.0 mL, 52.0 mmol, 1.2 eq.) Was added and the reaction mixture was then brought to 0 ° C. After 30 min, an aqueous solution of 3.00 M sodium hydroxide (18.0 mL) and 30% hydrogen peroxide (5.00 mL) was added dropwise. The reaction mixture was allowed to reach 25 ° C overnight. After the addition of water (100 mL), the organic phase was separated and the organic phase (layer) was extracted with dichloromethane (3 x 50.0 mL). The organic layers were dried over sodium sulfate before being evaporated. Purification on a chromatography column gave (9.6 g, 29.1 mmol, 64%) a slightly yellow oil.

1 H NMR (CDCl ₃ , 400 MHz): δ = 7.77 (dd, J = 8.3, 1.3 Hz, 1H), 7.47 (dt, J = 7.7, 1.4 Hz, 1 H), 7.36 (dt, J = 8.0, 1.7 Hz, 1H), 7.29 (dd, J = 7.5, 1.7 Hz, 1H), 7.28 ( dd, J = 7.7, 1.3 Hz, 1H), 7.19 (t, J = 8.3 Hz, 1H), 6.97 (dd, J = 8.3, 1.1 Hz). , 1H), 4.59 (s, 1H).

1 ³ C NMR (CDCl3, 101 MHz): δ = 156.4, 142.0, 136.1, 131.2,

130.8, 129.9, 129.5, 127.0, 122.7, 117.5, 116.8,

Ci ₂ H ₈ Br ₂ O (328.00):% calculated C 43.94, H 2.46; found C 44.19, H 2.57, 2) The phenol was then dissolved in acetone (100 mL). Potassium carbonate (6.00 g, 45.0 mmol, 1 eq) and iodomethane (7.76 g, 3.40 mL, 1.2 eq) were added successively. The mixture was heated at 60 ° C overnight. After cooling to 25 ° C, water (50.0 mL) was added and the organic layer was extracted with dichloromethane (4 x 100 mL). The combined organic layers were dried, filtered and evaporated. The crude product was purified by chromatography to give 2 ', 6-dibromo-2-methoxy-1,1'-biphenyl (11.6 g, 34.0 mmol, 95%) as a light solid. yellow. Melting point 93-95 ° C. 1H NMR (CDCl3, 300 MHz): δ = 7.60 (dd, J = 7.9, 1.0Hz, 1H), 7.38 (td, J = 7.4, 1.2Hz, 1H NMR (CDCl3):? H), 7.2 (m, 4H), 6.86 (dd, J = 7.9, 1.3 Hz, 1H), 3.66 (s, 3H).

¹³ C NMR (CDCl3, 75 MHz): δ = 158.0, 138.9, 132.5, 131.5, 131.3, 130.0, 129.2, 127.2, 124.7, 124, 6, 124.4, 109.9, 56.2,

Ci ₃ HioBr ₂ O (342.03):% calculated C 45.32, H 2.95; found C 45.32, H 2.85,

Example 10 Synthesis of (2 ', 6-dibromo-1,1'-biphenyl-2-yl) dimethylamine

1) At -78 ° C, butyllithium (16.3 mmol, 1 eq) in hexane (10.6 ml) was added dropwise to a solution of 2,2 ', 6-tribromobiphenyl (6 36 g, 16.3 mmol, 1 eq.) In THF (33.0 mL). Benzenesulfonyl azide (2.98 g, 16.3 mmol, 1 eq) was added dropwise and after one hour the reaction mixture was allowed to reach 25 ° C. It was treated with distilled water (40 mL) and the aqueous phase was extracted with ethyl acetate (3 x 40 mL). The combined organic layers were dried, filtered and evaporated. 6-Azido-2,2'-dibromobiphenyl was obtained as a brown viscous oil which was used for reduction of the azide without further purification.

1 H NMR (300 MHz, CDCl ₃ ): δ = 7.72 (d, J = 1.3 Hz, 1H), 7.64 (d, J = 2.6 Hz, 1H), 7.40 ( td, J = 7.5, 1.2 Hz, 2H), 7.29 (d, J = 1.5 Hz, 2H), 7.26 (d, J = 0.9 Hz, 1H) .

1 ³ C NMR (CDCl ₃ , 75 MHz): δ = 117.4, 124.4, 124.8, 125.1,

128.8, 130.7, 130.8, 131.7, 131.8, 139, 139.9, 142.0,

v (film): 2102.91 cm ^-1 (N ₃ ).

2) A solution of 6-azido-2,2'-dibromobiphenyl (5.75 g, 16.3 mmol, 1 eq) in diethyl ether (150 mL) was added slowly via a cannula to a stirred solution of Lithium aluminum hydride (0.64 g, 16.8 mmol, 1.05 eq) in diethyl ether (150 mL). After the addition was complete, the reaction mixture was heated at 50 ° C for 4.5 h. It was cooled to room temperature and mixed with diethyl ether (100 mL) and water (200 mL). The solution was filtered through a sintered glass. The aqueous phase was extracted with diethyl ether (2 x 80.0 mL) and the combined organic layers were dried and evaporated. 6,2'-Dibromobiphenyl-2-ylamine was obtained as an orange crystalline solid which was directly used for the methylation of the amine without further purification. Melting point: 63-66 ° C.

1 H NMR (300 MHz, CDCl ₃ ): δ = 7.74 (dd, J = 7.8, 0.9 Hz, 1H), 7.46 (td, J = 7.5, 1.2 Hz, 1 H), 7.33 (dd, J = 7.5, 1.8 Hz, 1H), 7.28 (dd, J = 6.9, 1.8 Hz, 1H), m, 2H), 6.70 (dd, J = 6.9, 2.1, 1H), 3.5 (s, 2H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 114.1, 122.1, 124.5, 124.6, 127.3, 128.2, 129.9, 130.0, 131.8, 133 , 2, 138.8, 145.0,

Ci ₄ H ₃ Br ₂ N (355.07):% calculated C 47.36, H 3.69, N 3.95; found C 48.00, H 3.84, N 3.62,

3) Sodium cyanoborohydride (2.04 g, 48.0 mmol, 3 eq) was added in small amounts to a stirred solution of 2 ', 6-dibromobiphenyl-2-ylamine (5.68 g, 16, 0 mmol, 1 eq.) And a 37% aqueous solution of formaldehyde (13.0 mL, 160 mmol, 10 eq.) In acetonitrile (64.0 mL) placed in a cold bath. Glacial acetic acid (1.76 mL, 18.0 mmol, 1.7 eq.) Was added very slowly and the reaction mixture was stirred at room temperature for 2 hours. An additional portion of glacial acetic acid (1.76 mL, 18.0 mmol, 1.7 eq.) Was added and stirring was continued for an additional 2 hours. The reaction mixture was poured into diethyl ether (200 mL) and then washed with 1N potassium hydroxide (3 x 60.0 mL) and brine (1 x 60.0 mL). The organic phase was dried and evaporated under vacuum. The crude product was subjected to silica gel chromatography using a 9: 1 mixture of ethyl acetate and cyclohexane. (2 ', 6-Dibromobiphenyl-2-yl) dimethylamine (4, 56 g, 12.8 mmol, overall yield: 79%) as yellow crystals. Melting point: 67-69 ° C.

1H NMR (300 MHz, CDC1 _3): δ = 7.65 -7.72 (m, 1 H), 7.30 -7.44 (m, 2H), 7.15 -7.29 (m, 3H), 7.06 (d, J = 8.1 Hz, 1H), 2.54 (s, 6H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 153.8, 141.4, 135.4, 132.7, 132.2, 129.6, 128.8, 127.2, 125.9, 125 , 5, 125.2, 117.9, 43.6 (2 C).

Ci ₄ Hi ₃ Br ₂ N (355.07):% calculated (%): C 47.36, H 3.69, N 3.95; found C 48.12, H 3.91, N 3.79, Example 11 Synthesis of 2,2'-dibromo-6-phenylbiphenyl

To a solution of 2,2'-dibromo-6-iodobiphenyl (3.88 g, 8.86 mmol, 1 eq), sodium carbonate (5.63 g, 53.2 mmol, 6 eq.), of phenylboronic acid (2.16 g, 17.7 mmol, 2 eq) in acetonitrile (130 mL) and water (130 mL) was added Pd (PPh ₃ ) ₄ (0.51). 0.44 mmol, 5 mol%). The mixture was heated at 90 ° C for 3 h and brought to 25 ° C. Water (100 mL) was added followed by ethyl acetate (4 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The dark brown oil was purified by silica gel filtration with cyclohexane as eluent to provide a colorless oil (3.33 g, 8.58 mmol, 95%).

1 H NMR (CDCl ₃ , 300 MHz): δ = 7.61 (dd, J = 7.5, 1.7 Hz, 1H), 7.44 (dd, J = 7.7, 1.1 Hz, 1H), 7.3-7.2 (m, 2H), 7.1-7.0 (m, 6H), 7.0-6.9 (m, 2H).

¹³ C NMR (CDCl ₃ , 75 MHz): δ = 143.6, 141.2, 140.5, 140.3, 132.3, 131.9, 131.6, 129.6, 129.3, 129 , 1, 129.0, 127.6, 127.4, 127.0, 126.9, 124.8, 124.7,

MS (EI): m / z (%) = 388 (7) [M ⁺ ], 308 [M ⁺ -Br], 228 [M ⁺ - 2 Br].

General procedure for the synthesis of diiodobiaryls for catalytic phosphination: Conditions e:

 At -78 ° C, butyllithium (2 eq) in hexane was added dropwise to a solution of dibromobiaryl (1 eq) in THF (40.0 mL per 10.0 mmol). After 1 h, a solution of iodine (2 eq) in THF was added to the solution and the solution was brought to room temperature. After the addition of a saturated aqueous solution of sodium thiosulfate, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 x 30.0 mL). The combined organic layers were dried over sodium sulfate and evaporated.

Conditions f: At -78 ° C, tert-butyllithium (4 eq) in pentane was added dropwise to a solution of dibromobiaryl (1 eq) in THF (20.0 mL for 5.00 mmol). After 1 h, a solution of iodine (2 eq) in THF was added and the reaction mixture was allowed to reach 25 ° C. After the addition of water, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated.

Example 12 Synthesis of 2,2'-Diiodobiphenyl

Prepared under the conditions e) above and starting from 2,2'-dibromobiphenyl (according to TK Daugherty et al., J. Org Chem 1983, 48, 5273), 2,2'-diiodobiphenyl (88%) under the form of a white solid (melting point: 92 - 94 ° C)

¹ H NMR (CDCl ₃ , 300 MHz): δ = 7.87 (d, J = 7.91 Hz, 2H), 7.34 (td, J = 7.50, 0.94 Hz, 2H) , 7, 12 (dd, J = 7.59, 1.60 Hz, 2H), 7.01 (td, J = 7.57, 1.59 Hz, 2H).

¹³ C NMR (75 MHz, CDCI ₃ ): δ = 148.95 (2 C), 138.90 (2 C), 129.91 (2 C), 129.27 (2 C), 127.95 (2 C), 99.62 (2 C).

HRMS for Ci ₂ H ₈ I _2: calculated 405.8715; found 405.8781

Example 13 Synthesis of 2,2'-diiodo-6-fluorobiphenyl

Prepared under the conditions f) above starting from 2,2'-dibromo-6-fluorobiphenyl. The crude product was subjected to flash chromatography on silica gel using cyclohexane. 2,2'-Diiodo-6-fluorobiphenyl (80%) was obtained as a colorless solid (mp 104-106 ° C).

¹ H NMR (CDCl3, 300 MHz): δ = 7.91 (dd, J = 7.9, 1, 1 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.41 (td, J = 7.6, 1.1 Hz, 1H), 7.05-7.15 (m, 2H), 6.81 (d, J = 8.4 Hz, 2H). ).

¹³ C NMR (75 MHz, CDC1 _3): δ = 158.9 (d, J = 250.5 Hz), 143.5, 139, 1, 136.9 (d, J = 18.7 Hz), 134 , 6 (d, J = 3.6 Hz), 131.0 (d, J = 8.5 Hz), 130.5, 130.2, 128.3, 1 15.7 (d, J = 22.6 Hz), 100.8 (d, J = 1.5 Hz), 99.8 (d, J = 0.9 Hz). HRMS for Ci ₂ H ₇ FI _2: calculated 423.8616; found 423,8635

Example 14 Synthesis of 2,2'-diiodo-6-chlorobiphenyl Prepared under the conditions e) above and starting from 2,2'-dibromo-6-chlorobiphenyl. The crude product was flash chromatographed on silica gel using cyclohexane and 2,2'-diiodo-6-chlorobiphenyl (93%) was obtained as a colorless solid (mp. melting: 63-65 ° C). 1 H NMR (CDC1 _3, 300 MHz): δ = 7.97 (dd, J = 7.92, 0.96 Hz, 1

H), 7.87 (dd, J = 7.95, 1.03 Hz, 1H), 7.47 (td, J = 8, 18, 1, 16Hz, 2H), 7, 1-7. , 2 (m, 2H), 7.04 (t, J = 7.99, Hz, 1H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 147.4, 146.7, 139, 1, 137.5, 133.5, 130.5, 129.9, 129.8, 129.5, 128 , 5, 100.8, 99.4,

HRMS for Ci ₂ H ₇ CLI _2: calculated 438.8329; found 438.8377

Example 15 Synthesis of 2,2'-diiodo-6-bromobiphenyl

Prepared under conditions e) and starting from 2,2 ', 6-tribromobiphenyl. The crude product was subjected to flash chromatography on silica gel using cyclohexane and 2,2'-diiodo-6-bromobiphenyl (93%) was obtained as a colorless solid (m.p. melting: 63-65 ° C).

¹ H NMR (CDCl3, 300 MHz): δ = 7.89 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 8.9 Hz, 1H), 7.60 ( d, J = 8.0 Hz, 1H), 7.37-7.42

(m, 1H), 7.0-7.1 (m, 2H), 6.87 (t, J = 8.0, 1H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 149, 1, 148,2, 139, 1, 138.2, 132.6, 130.6, 129.9 (2 C), 128.5, 123 , 2, 100.4, 99.3, Example 16: Synthesis of 2,2'-diiodo-6-methylbiphenyl

Prepared under the conditions f) above starting from 2,2'-dibromo-6-methylbiphenyl. The crude product was flash chromatographed on silica gel using cyclohexane and 2,2'-diiodo-6-methylbiphenyl (86%) was obtained as a white solid (mp. melting: 78-81 ° C). ¹ H NMR (CDCl ₃ , 300 MHz): δ = 7.88 (d, J = 7.94 Hz, 1H), 7.71 (d, J = 7.90 Hz, 1H), 7.38 (td, J = 7.55, 1.10 Hz, 1H), 7.18 (t, J = 3.15 Hz, 1H), 7.01-7.06 (m, 2H), 6, 92 (t, J = 7.77Hz, 1H), 2.06 (s, 3H).

¹³ C NMR (75 MHz, CDCI ₃ ): δ = 148.7, 148.0, 139.2, 137.8, 136.5, 129.9, 129.8, 129.6, 129.3, 128 , 6, 100.7, 100.0, 21.9,

HRMS for Ci ₃ Hi ₀ I _2: calculated 419.8866; found 419.8876

Example 17: Synthesis of 2,2'-diiodo-6-methoxybiphenyl Prepared under the conditions f) above from 2,2'-dibromo-6-methoxybiphenyl. Trituration of the crude product in methanol gives 2,2'-diiodo-6-methoxybiphenyl (71%) as a white solid (mp 125-127 ° C). 1 H NMR (CDCl ₃ , 300 MHz): δ = 7.87 (d, J = 7.9 Hz, 1H), 7.49

(d, J = 7.9 Hz, 1H), 7.36 (td, J = 7.5, 1.1 Hz, 1H), 7.07 (dd, J = 7.6, 1.6), Hz, 1H), 7.0-6.9 (m, 2H), 6.88 (d, J = 8.3 Hz, 1H), 3.66 (s, 3H).

¹³ C NMR (CDCl ₃ , 75 MHz): δ = 157.2, 146.3, 138.9, 137.9, 131.0, 130.6 (2C), 129.3, 128.3, 111, 0, 101.4, 100.8, 56.2,

Example 18 Synthesis of 2,2'-diiodo-6-dimethylaminobiphenyl

Prepared under the conditions f) above starting from 2,2'-dibromo-6-dimethylaminobiphenyl. Trituration of the crude product with methanol gave (6,2'-diiodobiphenyl-2-yl) dimethylamine (65%) as a colorless powder (m.p .: 80-81 ° C).

1 H NMR (CDCl ₃ , 300 MHz): δ = 7.87 (d, J = 7.9 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.36 ( t, J = 7.5 Hz, 1H), 7.2-7.1 (m, 1H), 7.0-6.9 (m, 3H), 2.44 (s, 6H) .

¹³ C NMR (CDCl ₃ , 75 MHz): δ = 153.1, 148.4, 142.5, 139.2, 132.9, 131.7, 130.1, 128.8, 128.0, 119 , 4, 102.7, 102.1, 43.7 (2 C). Example 19 Synthesis of 2,2'-diiodo-6-trifluoromethoxybiphenyl

Prepared under the conditions f) above starting from 2,2'-dibromo-6-trifluoromethoxybiphenyl. The crude product was purified by chromato graphy to give 2,2'-diiodo-6-trifluoromethoxybiphenyl (81%) as a colorless oil.

1H NMR (CDCl3, 300 MHz): δ = 7.89 (dd, J = 7.9, 0.9 Hz, 1H), 7.83 (dd, J = 7.9, 1.0 Hz, 1 H), 7.38 (td, J = 7.5, 1.1 Hz, 1H), 7.3-7.2 (m, 2H), 7.1-7.0 (m, 2H); ).

¹³ C NMR (CDCl3, 75 MHz): δ = 146.4 (d, J = 1.5 Hz), 144.3,

141.7, 139.0, 137.2, 130.7, 130.3, 129.9, 128.2, 120.3 (q, J = 258.9 Hz), 120.1 (d, J = 1, 7 Hz), 101.7, 99.5, Example 20: Synthesis of 2,2'-Diiodo-6-phenylbiphenyl

Prepared under the conditions f) above starting from 2,2'-dibromo-6-phenylbiphenyl. Crystallization with methanol gave 2,2'-diiodo-6-phenylbiphenyl (44%) as colorless crystals (m.p .: 109-111 ° C).

1H NMR (CDCl3, 300 MHz): δ = 7.89 (dd, J = 7.9, 1.0 Hz, 1H), 7.69 (dd, J = 7.9, 0.8 Hz, 1H NMR (CDCl3, 300 MHz):? H), 7.31 (dd, J = 7.7, 1.0 Hz, 1H), 7.18 (td, J = 7.0, 1.0 Hz, 1H), 7.1-7. , 0 (m, 6H), 6.99 (dd, J = 7.6, 1.6 Hz, 1H), 6.83 (td, J = 7.7, 1.7 Hz, 1H) .

¹³ C NMR (CDCl3, 75 MHz): δ = 148.1, 146.7, 142.8, 140.7,

138.8, 138.2, 131.4, 130.2, 129.6, 129.4 (2 C), 128.9, 127.7, 127.5 (2 C), 127.0, 101.8, 101.5,

Representative Examples of Syntheses of Compounds Having a General Formula Type II:

General procedure for synthesis of dibromobiaryls or bromoiodobiaryls used as starting materials: Conditions g:

 At -78 ° C, tert-butyllithium (2 eq) in pentane was added dropwise to a solution of substrate (1 eq) in THF over a period of 2 h. After 1 h, 1,2-dibromobenzene (1 eq) was added dropwise and the reaction mixture was allowed to reach 25 ° C. Water was added followed by extraction with ethylacetate. The combined organic layers were dried, filtered and evaporated. Example 21 Synthesis of 6-Bromo-2,2,3,3-tetrafluoro-5- (2-iodophenyl) -2,3-dihydro-benzo [1,4] dioxin

Synthesized under conditions a) and starting from 6-bromo-2,2,3,3-tetrafluoro-5-iodo-2,3-dihydrobenzo [1,4] dioxin. The residue was purified by silica gel chromatography to give 6-bromo-2,2,3,3-tetrafluoro-5- (2-iodophenyl) -2,3-dihydro-benzo [1,4] dioxin (40%) as a colorless oil.

1 H NMR (CDCl ₃ , 300 MHz): δ = 7.90 (dd, J = 8.0, 1.0 Hz, 1H), 7.43 (d, J = 8.9 Hz, 1H), 7.40 (td, J = 7.6, 1.0 Hz, 1H), 7.10 (td, J = 7.3,

1.7 Hz, 2H), 7.03 (d, J = 8.5 Hz, 1H).

¹³ C NMR (CDCl3, 100 MHz): δ = 139.7, 139.3, 137.0, 134.8, 130.4, 130.3, 129.0, 128.5, 120.0 (2 C) ), 118.3, 112.1 (tt, J = 269.8, 40.0 Hz), 99.1,

MS (EI): m / z (%) = 489.9 (54) [M ⁺ ], 408.9 (100) [M ⁺ -Br], 360.9

(24) [M ⁺ - 1], 216.0 (36) [M ⁺ - 1 - Br - OCF ₂ ].

Example 22 Synthesis of 5-bromo-2,2-difluoro-4- (2-iodophenyl) benzo [1,3] dioxole

Synthesized under conditions b) starting from 5-bromo-2,2-difluoro-4-iodobenzo [1,3] dioxole. The residue was purified by silica gel chromatography to give 5-bromo-2,2-difluoro-4- (2-iodophenyl) benzo [1,3] dioxole (66%) as a yellow oil. 1H NMR (CDCl3, 300 MHz): δ = 7.90 (d, J = 7.9 Hz, 1H), 7.40 (td, J = 7.5, 1.0 Hz, 1H), 7 , (D, J = 8.5 Hz, 1H), 7.2-7.1 (m, 1H), 7.11 (td, J = 7.7, 1.7 Hz, 1H) , 6.93 (d, J = 8.5 Hz, 1H).

¹³ C NMR (CDCl3, 75 MHz): δ = 142.9 (2 C), 139.4, 138.9 (2 C), 135.1 (t, J = 250 Hz), 130.6, 130, 6, 128.4, 127.3, 117.8, 110.3, 99.1,

MS (EI): m / z (%) = 437.99 (42) [M ⁺ ], 358.9 (100) [M ⁺ -O ₂ CF ₂ ].

Example 23 Synthesis of 5-bromo-4- (2-bromophenyl) benzo [1,3] dioxole

Synthesized under conditions g) and starting from 5-bromo-4-iodobenzo [1,3] dioxole. The residue was purified by flash chromatography to give 5-bromo-4- (2-bromophenyl) -benzo [1,3] dioxole (90%) as a white solid (mp 75-77). ° C).

1H NMR (CDCl3, 300 MHz): δ = 7.62 (dd, J = 8.9, 1.7 Hz, 1H), 7.33 (td, J = 7.2, 1.1 Hz, 1H NMR (CDCl3, 300 MHz):? H), 7.3-6.9 (m, 2H), 7.08 (d, J = 8.3 Hz, 1H), 6.68 (d, J = 8.3 Hz, 1H) , 5.99 (dd, J = 5.3, 1.3 Hz, 2H).

¹³ C NMR (CDCl3, 75 MHz): 146.9, 146.4, 136.3, 132.8, 131.6, 130.0, 127.4, 125.1, 124.1, 123.8, 114.9, 109.2, 101.9,

Procedures for the synthesis of diiodobiaryls for catalytic phosphination:

Example 24 Synthesis of 5-iodo-4- (2-iodophenyl) benzo [1,3] dioxole

Prepared under the conditions e) above and starting from 2-bromo-4- (2-bromophenyl) benzo [1,3] dioxole. Purification by chromatography on silica gel with cyclohexane gives 5-iodo-4- (2-iodophenyl) -benzo [1,3] dioxole (91%) as colorless crystals (m.p .: 124-128 °). VS).

1H NMR (CDCl3, 300 MHz): δ = 7.89 (dd, J = 8.0, 1.0 Hz, 1H), 7.4-7.3 (m, 2H), 7.14 ( dd, J = 7.6, 1.6 Hz, 1H), 7.05 (td, J = 7.9, 1.7 Hz, 1H), 6.58 (d, J = 8.2 Hz). , 1H), 5.89 (dd, J = 7.1, 1.3 Hz, 2H). ^li C NMR (CDCl3, 75 MHz): δ = 148.1, 145.6, 143.3, 139.2, 131.6, 130.7, 130.2, 130.1, 128.4, 110, 2, 101.8, 100.1, 89.1,

Example 25 Synthesis of 5-iodo-2,2'-difluoro-4- (2-iodophenyl) benzo [1,3] dioxole

Prepared under conditions f) starting from 5-bromo-2,2-difluoro-4- (2-iodophenyl) benzo [1,3] dioxole. The crude product was subjected to flash chromatography on silica gel using cyclohexane and 5-iodo-2,2'-difluoro-4- (2-iodophenyl) benzo [1,3] dioxole (69%). ) was obtained as a yellow oil.

¹ H NMR (CDCl3, 300 MHz): δ = 7.91 (dd, J = 7.88, 1.06 Hz, 1 H), 7.61 (dd, J = 8.41 Hz, 1H), 7.41 (td, J = 7.57, 1.07 Hz, 1H), 7.05-7.15 (m, 2H), 6.82 (d, J = 8.4 Hz, 1H). ).

HRMS for Ci ₃ H ₆ F ₂ I ₂ 0 _2: calculated 485.8420; found 485,8404

Compounds having a general formula of type III and IV may be obtained by conventional methods. For example by using dibromo compounds which will be subjected to a bromine / lithium exchange sequence and trapping with the diiod to obtain the necessary monoiodo precursor. The skilled person will easily adapt, including through his general knowledge, synthesis methods accordingly.

 More particularly, the di, tri or tetrahalobiaryl compounds according to the invention are characterized in that they are chosen from the group formed by: a) compounds of formula I in which:

R ¹ represents Br or I,

R ² represents Br or I, and

R ³ represents H, F, Cl, Br, I, CH ₃ , OCH ₃ , N (CH ₃ ) ₂ , OCF ₃ , or Ph,

R ⁴ representing H,

 or

R ⁴ representing Cl when R ³ = C1, R ^{1 =} Br and R ² = I or,

R ⁴ representing Br when R ³ = H ₃ CO and R ^{1 =} R ² = I, b) compounds of formula II in which R ¹ , R ² and R ⁴ have the meanings given for formula I, and

R ³ is selected from the group consisting of saturated chains O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O, c) compounds of formula III in which

R ¹ and R ² have the meanings given for formula I, and

R ³ and R ⁴ are independently selected from the group consisting of saturated O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O chains.

Thanks to the process according to the invention, new di or triphosphine biaryl compounds derived from compounds of formula I, II, III or IV are obtained. Not part of it, the compounds

 of formula I in which:

R ¹ = R ² = PPh ₂ and R ³ = H, CH ₃ , OH, or OCH ₃ and R ⁴ = H;

 * of formula II in which:

R ¹ = R ² = PPh ₂ and R ^{3 '} = (CH ₂ ) ₄ and R ⁴ = H,

 * of formula III in which:

R ¹ = R ² = PPh ₂ and R ^{3 '} = R ₄ = O-CH ₂ -O or O- (CH ₂ ) ₂ -O or O-CF ₂ -O,

of formula IV in which R ^{1 =} R ² = PPh ₂ ,

Some of these new biaryl compounds according to the invention are characterized in that its formula I or III satisfies R ^{1 =} R ² and simultaneously R ³ = R ⁴ or R ^{3 '} = R ^4' .

 Preferably, said compounds are further characterized in that all the phosphine groups present are -PPh2 groups.

 The following compounds are new and form part of the invention:

 (6- (fluoro) biphenyl-2,2'-diyl) bis (diphenylphosphine)

 - (6-chlorobiphenyl-2,2'-diyl) bis (diphenylphosphine)

 6-methylbiphenyl-2,2'-diyl) bis (diphenylphosphine):

 2 ', 6'-bis (diphenylphosphino) -N, N-dimethylbiphenyl-2-amine

(6- (trifluoromethoxy) biphenyl-2,2'-diyl) bisdiphénylphosphine 2,2'-bisdiphenylphosphino-6-phénylbiphényle

 2- (5 - (Diphenylphosphino) benzo [d] [1,3] dioxo-4-yl) phenyl) diphenyl phosphine

 (2- (5- (diphenylphosphino) -2,2-difluorobenzo [(i] [1,3] dioxol-4-yl) phenyl) diphenyl phosphine

 (2- (6- (diphenylphosphino) -2,2,3,3-tetrafluoro-2,3-dihydrobenzo

 [δ] [1,4] dioxin-5-yl) phenyl) diphenylphosphine

 6'-methoxybiphenyl-2,2 ', 6-triyl) tris (diphenylphosphine)

Examples of process according to the invention

General description of the phosphination process:

 Phosphofluorène

The vacuum was made in an oven-dried Schlenk tube before filling it with argon. Potassium acetate (2.20 mmol, 0.22 g, 2.2 eq), the diiodo-biaryl compound (1.00 mmol, 1 eq) and diphenylphosphine (2.20 mmol, 0, 41 g, 0.38 mL, 2.2 eq.) Were added to a solution of N, N-dimethylacetamide or DMA (9.00 mL) followed by a solution of N, N-dimethylacetamide (1.00 mL). ) containing palladium acetate (1.50 mg, 2 mol%). The solution turned red and immediately placed in an oil bath at 130 ° C. After completion of the reaction, after 0.5 or 1 or 1.5 or 2 or 3 hours, the reaction mixture was allowed to reach room temperature. Water (40 mL) was added and the aqueous phase was extracted with dichloromethane (3 x 50.0 mL). The combined organic layers have been dried over sodium sulfate. Evaporation of the solvent followed by chromatography on silica gel with cyclohexane / ethyl acetate (19: 1) yielded the corresponding bis (diphenylphosphino) biphenyl. Example with 2,2'-bis (diphenylphosphino) biphenyl:

Prepared from 2,2'-diiodobiphenyl. Purification by chromatography yielded 2,2'-bis (diphenylphosphino) biphenyl (0.62 mmol, 0.34 g, 62%) as a colorless powder (mp 211 ° -122 ° C.) .

1H NMR (300 MHz, CDC1 _3): δ = 7.2 (m, 22 H), 7.07 (td, J = 7.5, 1.5 Hz, 2H), 7.03 (d, J = 7.5 Hz, 2H), 6.79 (d, J = 7.5 Hz, 2H).

3 ¹ P NMR (161 MHz, CDCl ₃ ): δ = -14.01 (s, broad).

HRMS for C ₃₆ H ₂ 8P ₂ [M + H]: calculated value 523.1739; found 523.1707

Example with (6- (fluoro) biphenyl-2,2 '- (iiyl) bis ((iiplienylpliospliin)

Prepared from 2,2'-diiodo-6-fluorobiphenyl or 2-bromo-6-fluoro-2'-iodobiphenyl. Purification by chromatography gave (6- (fluoro) biphenyl-2,2'-diyl) bisdiphenylphosphine (0.73 mmol, 0.39 g, 73% and 70%, respectively) as a colorless powder. (mp: 184-185 ° C). 1H NMR (300 MHz, CDC1 _3): δ = 7,2- 7,4 (m, 23 H), 7,0- 7,1 (m,

2H), 6.91 (dd, J = 7.7, 3.1 Hz, 1H), 6.86 (dd, J = 7.5, 4.9 Hz, 1H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 160.0 (ddd, J = 246.6, 9.9, 1.4 Hz, 1 C), 147.4 (t, J = 18.8 Hz , 1 C), 140.8 (dd, J = 32.5, 7.1 Hz, 1 C), 140.4 (d, J = 13.1 Hz, 1 C), 137.9 (d, J = 13.8 Hz, 1 C), 137.6 (d, J = 10.7 Hz, 1 C), 137.3 (d, J = 12.5 Hz, 1 C), 137.2 (d, J) = 12.7 Hz, 1 C), 136.8 (d,

J = 13.6 Hz, 1 C), 134.4 (d, J = 1.7 Hz, 1 C), 134.4 (s, 1 C), 134.1 (s, 1 C), 134, 0 (s, 1 C), 133.9 (d, J = 2.5 Hz, 1 C), 133.7 (m, 2 C), 133.5 (d, J = 1.2 Hz, 1 C). ), 133.2 (d, J = 1.2 Hz, 1 C), 131.2 (dd, J = 5.8, 3.1 Hz, 1 C), 129.6 (dd, J = 3, 0, 1.5 Hz, 1 C), 129.3 (d, J = 8.0 Hz, 1 C), 128.81 (s, 1 C), 128.0-128.5 (m, 14 C). ) ³¹ P NMR (CDCl ₃ , 161 MHz): δ = -12.03 (dd, J = 25.5, 18.7 Hz), - 13.30 (dd, J = 25.6, 10.7 Hz) .

HRMS for C ₃₆ H ₂₇ FP ₂ [M + K]: calculated value 579.1204; found value 579.1621,

Example with (6-chlorobiphenyl-2,2'-diyl) bis (diphenylphosphine)

Prepared from 2,2'-diiodo-6-chlorobiphenyl, the crude product was purified by chromatography on silica gel using cyclohexane as eluent and yielded (6-chlorobiphenyl-2,2'-diyl) bis (diphenylphosphine) (0.95 mmol, 0.53 g, 95%) as a colorless solid (mp 158 ° -159 ° C.).

1 H NMR (300 MHz, CDCl ₃ ): δ = 7.4-7.0 (m, 23H), 6.84 (qd, J = 2.9, 1.1 Hz, 1H), 6.8 -6.7 (m, 2H), 6.57 (qd, J = 4.3, 0.9 Hz, 1H).

1 ³ C NMR (75 MHz, CDCI ₃ ): δ = 145.4-144.4 (m, 2 C), 140.8 (dd,

J = 14.3, 2.2 Hz, 4 C), 137.9 (d, J = 14.6 Hz), 137.5 (dd, J = 12.6, 1.1 Hz), 136.9. (d, J = 12.4 Hz), 136.9 (dd, J = 10.5, 1.5 Hz), 136.5 (dd, J = 13.2, 1.0 Hz), 134.9. (d, J = 2.6 Hz), 134.8 (d, J = 2.3 Hz), 134.4, 134.1, 134.1- 134.0 (m, 3 C), 133.8 -133.7 (m, 2 C), 133.3, 133.1, 132.2, 130.8 (dd, J = 6.3, 3.2 Hz), 129.7, 128.8, 127 , 7, 128.3-128.0 (12 C).

³¹ P NMR (161 MHz, CDCl3): δ = -11.3 (d, J = 22.4 Hz), -13.48 (d, J = 22.4 Hz).

MS (EI): m / z (%) = 555.3 (<1) [M ⁺ ], 521.1 [M ⁺ -Cl], 479.1 (1) [M ⁺ -ph], 443.1 (<1) [M ⁺ - Cl - Ph], 371.1 (100) [M ⁺ - PPh ₂ ], 336 (6) [M ⁺ - PPh ₂ - Cl], 257.1 [M ⁺ - PPh ₂ - Cl - Ph], 183 (34) [M ⁺ - PPh ₂ - Cl - 2 Ph].

Example with (6-methylbiphenyl-2,2'-diyl) bis (diphenylphosphine):

Prepared from 2,2'-diiodo-6-methylbiphenyl, the crude product was purified by silica gel chromatography using cyclohexane as eluant and yielded (6-methylbiphenyl-2,2'-diyl) bis (diphenylphosphine) (0.73 mmol, 0.39 g, 73%) as a colorless powder (mp 181-182 ° C). 1H NMR (300 MHz, CDC1 _3): δ = 7.3-7.0 (m, 22 H), 7.0 to 6.9 (m, 1H), 6.92 (td, J = 6, 9, 1.6 Hz, 2H), 6.9-6.8 (m, 1H), 6.54 (q, J = 7.4, 4.5 Hz, 1H), 1.61 ( s, 3H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 146.6 (dd, J = 6.5, 1.7 Hz), 146.2 (dd, J = 6.5, 3.7Hz), 138 , 8 (d, J = 14.1 Hz), 137.7 (d, J = 13.0 Hz),

137.5-137.4 (m, 2 C), 137.3, 137.1-136.9 (m, 2 C), 134.7, 134.5 (2 C), 134.4, 134, 2, 133.6 (d, J = 3.2 Hz), 133.4-133.3 (m, 2 C), 133.1 (d, J = 1.3 Hz), 131.3 (d, J = 1.0 Hz), 130.8 (dd, J = 3.0, 6.0 Hz), 130.5, 128.6, 128.4, 128.4-128.0 (10 C), 127.8, 127.7, 127.5, 20.6 (t, J = 2.6 Hz).

3 ¹ P NMR (161 MHz, CDCI ₃ ): δ = -12.1 (d, J = 27.0 Hz), -13.8 (d,

J = 27.0 Hz)

MS (EI): m / z (%) = 535.1 (<1) [M ⁺ ], 459.1 (1) [M ⁺ -ph], 351.1 (100) [M ⁺ -Ph ₂ ] , 337.1 (6) [M ⁺ - PPh ₂ - Me], 183.1 (42) [M ⁺ - PPh ₂ - Me - 2 Ph].

Example with (6- (methoxy) biphenyl-2,2'-diyl) bis (diphenyl phosphine)

Prepared from 2,2'-diiodo-6-methoxybiphenyl, the crude product was purified by silica gel chromatography using cyclohexane as eluant and yielded (6- (methoxy) -2,2-biphenyl pure di (diphenylphosphine) (0.98 mmol, 0.54 g, 98%) as a colorless powder (mp 181-182 ° C). 1 H NMR (CDCl ₃ , 400 MHz): δ = 7.3 (m, 18H), 7.15 (dt, J = 6.8,

2.6 Hz, 4H), 7.06 (dt, J = 7.3, 1.7 Hz, 2H), 6.82 (dd, J = 7.6, 4.2 Hz, 1H) , 6.77 (d, J = 8.2 Hz, 1H), 6.66 (dd, J = 7.9 Hz, 3.1, 1H), 3.22 (s, 3H).

¹³ C NMR (CDCl ₃ , 101 MHz): δ = 157.1 (d, J = 2 Hz), 144.1 (d, J = 8 Hz), 143.8 (d, J = 8 Hz), 138 , 3, 137.4, 136.3 (d, J = 8 Hz), 136.1 (d, J = 7 Hz), 134.5 (d, J = 2 Hz), 133.9 (dd, J) = 20, 14 Hz), 133.3 (d, J = 19

Hz), 131.2 (dd, J = 6.4 Hz), 128.8, 128.4, 128.2, 128.0, 127.9 (d, J = 2 Hz), 128.8, 127 , 6, 125.9 (d, J = 2 Hz), 110.6, 54.7,

³¹ P NMR (CDCl ₃ , 162 MHz): δ = -13.1 (d, J = 17.8 Hz), -13.6 (d, J = 17.8 Hz).

C ₃₇ H ₃₀ OP ₂ (552.59):% calculated: C 80.42, H 5.47; found: C

80.53, H 5.52, Example with 1,1'-bisidiphenylphosphinol-N-dimethylbiphenyl

2-amine Prepared from 6,2'-diiodobiphenyl-2-yl) dimethylamine, the crude product was purified by chromatography on silica gel using cyclohexane as eluent and yielded 2 ', 6' bis (diphenylphosphino) -N, N-dimethylbiphenyl-2-amine (0.43 mmol, 0.24 g, 43%) pure as a colorless powder (mp: 150-152 ° C).

1H NMR (300 MHz, CDC1 _3): δ = 7.3-7.1 (m, 20 H), 7.1 to 6.9 (m, 4H), 6.84 (td, J = 7, 0, 1.5 Hz, 2H), 6.71 (d, J = 5.8 Hz, 1H), 2.10 (s, 6H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 152.8 (dd, J = 6.2, 4.2 Hz), 139.7 (d, J = 14.2 Hz), 139.0 to 138 , 7 (m, 3 C), 138.3 (d, J = 14.3 Hz), 137.9-137.7 (m), 136.8 (d, J = 8.4 Hz), 136, 2 (d, J = 2.5 Hz), 134.2, 133.9,

133.5 (m, 2 C), 133.2 (m, 4 C), 132.9-132.7 (m, 2 C), 128.7-127.3 (m, 17 C), 119, 3, 42.2 (2 C).

³¹ P NMR (161 MHz, CDC1 _3): δ = -13.4 to 25 ° C

MS (EI): m / z (%) = 564.2 (<2) [M ⁺ ], 521.0 (<2) [M ⁺ -NMe ₂ ], 488.2 (3) [M ⁺ -Ph] ], 380.1 (100) [M ⁺ - PPh ₂ ], 364.1 (25) [M ⁺ - Me - PPh ₂ ],

336.1 (6) [M ⁺ - NMe ₂ - PPh ₂ ].

Example with (6- (trifluoromethoxy) biphenyl-2,2'-diyl) bisdiphenyl phosphine

Prepared from 2,2'-diiodo-6-trifluoromethoxybiphenyl, the crude product was purified by chromatography on silica gel using cyclohexane as eluant and yielded (6- (trifluoromethoxy) biphenyl-2,2 Bis (diethyl) bisdiphenylphosphine (0.52 mmol, 0.32 g, 53%) pure as a colorless powder (m.p. 179-180 ° C).

1H NMR (300 MHz, CDC1 _3): δ = 7,3- 7,0 (m, 23 H) 6,9 6,8 (m, 3H), 6.62 (d, J = 6, 7 Hz).

¹³ C NMR (75 MHz, CDC1 _3): δ = 147.1 147,3- (m, 1 C), 140.9 141,1- (m, 1 C), 140.7 (dt, 141.0 , 20.2), 137.8- 136.4 (m, 6 C), 134.6-133.1 (m, 8 C), 131.8, 131.3 (t, J = 4.7 Hz), 128.9, 128.8, 128.4- 128.1 (14 C), 120.2 (q , J = 258.0), 119.6 (d, J = 1.6 Hz).

³¹ P NMR (CDCl ₃ , 161 MHz): δ = -13.0 at 25 ° C.

MS (EI): m / z (%) = 606.1 (<2) [M ⁺ ], 529.2 (6) [M ⁺ -ph], 421.1 (100) [M ⁺ -Ph ₂ ] , 353.2 (3) [M ⁺ - PPh ₂ - 3 F], 336.2 (8) [M ⁺ - PPh ₂ -

OCF ₃ ], 260.3 (1 1) [M ⁺ - PPh ₂ - OCF ₃ - Ph], 183.1 (51) [M ⁺ - PPh ₂ - OCF ₃ - 2 Ph].

Example with 2,2'-bisdiphenylphosphino-6-phenylbiphenyl

Prepared from 2,2'-diiodo-6-phenylbiphenyl, purification by chromatography gave 2,2'-bisdiphenylphosphino-6-phenylbiphenyl as a white powder (m.p .: 85-86 ° C). ). 1H NMR (300 MHz, CDC1 _3): δ = 7.4 (m, 12H), 7,2- 6,9 (m, 14

H), 6.9 (ddd, J = 7.5, 3.6, 1.1 Hz, 1H), 6.9-6.8 (m, 1H), 6.55 (td, J = 6.9, 1.3 Hz, 2H), 6.48 (td, J = 6.5, 1.3 Hz, 2H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 146.6 (dd, J = 33.2, 7.8 Hz),

145.6 (dd, J = 32.4, 6.3 Hz), 142.1 (dd, J = 6.0, 2.5 Hz), 141.6 (t, J = 1.7 Hz), 139, 1 (d, J = 14.6 Hz), 138.6-138.3 (m, 2 C), 137.5 (d, J = 13.5 Hz),

136.7 (d, J = 13.8 Hz), 135.9 (d, J = 10.8 Hz), 135.4 (d, J = 2.5 Hz), 134.5- 134.1 (m, 4 C), 133.6, 133.2- 133.1 (2 C), 133.0- 132.9 (3 C), 131.0, 130.6 (2 C), 128.6, 128, 4- 128.2 (5C), 128.1-128.0 (5C), 127.7, 127.7, 127.6, 127.5 (3C), 126.2,

3 ¹ P NMR (CDCl3, 161 MHz): δ = -13.2 (d, J = 11.3 Hz), -14.4 (d,

J = 11.4 Hz).

MS (EI): m / z (%) = 598.2 (<1) [M ⁺ ], 413.2 (100) [M ⁺ -Ph ₂ ], 183.1 (22) [M ⁺ - PPh ₂ - 3 Ph]. Example with (2- (5- (diphenylphosphino) benzo [i]] [1,3] dioxol-4-yl) phenyl) diphenylphosphine

Prepared from 5-iodo-4- (2-iodophenyl) -benzo [1,3] dioxole, the crude product was purified by silica gel chromatography using cyclohexane as eluent to yield 5- (diphenylphosphino) benzo [d] [l, 3] dioxol 4-yl) phenyl) diphenylphosphine (0.80 mmol, 0.45 g, 80%) pure as a colorless powder (mp 160-161 ° C).

1H NMR (300 MHz, CDC1 _3): δ = 7.3-7.0 (m, 23 H), 6.82 (qd, J = 4.1, 1.2Hz, 1H), 6.65 (d, J = 8.0Hz, 1H), 6.51 (q, J = 8.0, 3.7Hz, 1H),

5.65 (d, J = 1.5 Hz, 1H), 5.07 (d, J = 1.5 Hz, 1H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 147.8, 146.2 (dd, J = 11.7, 1.9 Hz), 140.9 (dd, J = 31.5, 6.8 Hz), 138.3 (d, J = 12.4 Hz), 137.8-137.4 (m, 4 C), 137.0 (dd, J = 12.7, 0.8 Hz), 134 , 4, 134.1-134.0 (m, 3 C), 133.8, 133.7 (d, J = 1.5 Hz), 133.5 (d, J = 1.9 Hz), 133 , 4 (d, J = 1.6 Hz), 133.3 (d, J =

1.9 Hz), 130.9-130.7 (m, 1 C), 129.9 (dd, J = 9.2, 1.0 Hz), 128.5-127.9 (m, 16 C). ).

³¹ P NMR (161 MHz, CDCI ₃ ): δ = -11.7 (d, J = 27.5 Hz), -13.5 (d, J = 27.5 Hz).

MS (EI): m / z (%) = 565.1 (1) [M ⁺ ], 489.1 (5) [M ⁺ -ph], 381 (100)

[M ⁺ - PPh ₂ ], 353 (6) [M ⁺ - PPh ₂ - OCH ₂ ], 183.1 (25) [M ⁺ - PPh ₂ - 2 Ph - OCH ₂ 0].

Example with (2- (5- (diphenylphosphino) -2,2-difluorobenzo [i] [1,3] dioxol-4-yl) phenyl) diphenylphosphine

Prepared from 5-iodo-2,2'-difluoro-4- (2-iodophenyl) benzo [1,3] dioxole or 5-bromo-2,2-difluoro-4- (2-iodophenyl) benzo [ 1, 3] dioxole, the crude product was purified by chromatography on silica gel using cyclohexane as eluant to afford (2- (5- (diphenylphosphino) -2,2-difluorobenzo [(i]], 3] dioxol-4-yl) phenyl) diphenylphosphine (0.48 mmol, 0.29 g, 48% and 72%, respectively) Melting point: 153 - 154 ° C. 1H NMR (300 MHz, CDCl ₃ ) δ = 7.3-7.1 (m, 21H), 7.0-6.9 (m,

2H), 6.9-6.8 (m, 1H), 6.8- 6.7 (m, 2H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 143.8, 142.4 (d, J = 11.5 Hz), 139.2 (dd, J = 32.1, 6.6 Hz), 137 , 9 137.5 (m, 2 C), 137.1- 136.6 (m, 3 C), 134.5 (d, J = 1.8 Hz), 134.1, 133.9, 133 , 8-133.5 (4 C), 133.3 (d, J = 1.6 Hz), 131.3 (t, J = 255.4 Hz), 133.1 (d, J = 1.6). Hz), 130.8 (dd, J = 5.7, 3.1 Hz), 129.8 (d, J = 1.6 Hz), 129.0, 128.8, 128.6 (2 C), 128.5- 128.3 (12 C), 109.0,

³¹ P NMR (CDCl ₃ , 161 MHz): δ = -12.1 (dd, J = 28.6, 1.5 Hz), -13.5 (d, J = 28.7 Hz).

MS (EI): m / z (%) = 602.1 (<1) [M ⁺ ], 525.2 (8) [M ⁺ -ph], 417.1

(100) [M ⁺ - PPh ₂ ], 183.1 (51) [M ⁺ - 2 PPh ₂ - CF ₂ ].

HRMS for C ₃₇ H ₂₆ F ₂ O ₂ P ₂ [M + H]: Calculated: 603.1449; found value: 603.1378 Example with (2- (6- (diphenylphosphino) -2,2,3,3-tetrafluoro-2,3-dihydrobenzo [b] [1,4] dioxin-5-yl) phenyl) diphenylphosphine

Prepared from 5-bromo-2,2-difluoro-4- (2-iodophenyl) benzo [i] [1,3] dioxole, the crude product was purified by silica gel chromatography and (2-iodophenyl) benzo [1,3] dioxole. (6- (diphenylphosphino) -2,2,3,3-tetrafluoro-2,3-dihydrobenzo [b] [1,4] dioxin-5-yl) phenyl) diphenylphosphine (47%) was obtained in the form of a colorless solid (m.p .: 169-170 ° C).

1H NMR (300 MHz, CDC1 _3): δ = 7,3- 7,1 (21 H), 6.98 (d, J = 8.5 Hz, 1H), 6.8 6,9 (m , 2H), 6.79 (dd, J = 8.5, 2.6 Hz, 1H), 6.7-6.6 (m, 1H),

H).

¹³ C NMR (75 MHz, CDCI ₃ ): δ = 140.1 (dd, J = 32.9, 7.1 Hz), 137.7, 137.6, 137.4 (2 C), 137.3 , 136.7 (d, J = 11.0 Hz), 136.4-136.1 (2 C), 135.5 (d, J = 9.7 Hz), 135.0 (d, J = 2) , 1 Hz), 134.3, 134.0, 133.8, 133.8 (d, J = 2.9 Hz), 133.6, 133.5 (d, J = 3.0 Hz), 133 , 3 (d, J = 1.4 Hz), 133.1

(d, J = 1.4 Hz), 131.1 (dd, J = 6.1, 3.1, 1 Hz), 130.6, 129.0, 128.9, 128.6- 128.3 ( m, 11 C), 117.0, 112.1 (tt, J = 40.7, 267.4, 2 C).

³¹ P NMR (CDCl ₃ , 161 MHz): δ = -13.3 (ddd, J = 24.6, 4.7, 2.1 Hz), -14.0 (d, J = 24.7 Hz) .

MS (EI): m / z (%) = 652.6 (<1) [M ⁺ ], 575.1 (2) [M ⁺ - Ph], 467.1

(100) [M ⁺ - PPh ₂ ], 183.1 [M ⁺ - 2 PPh ₂ - C ₂ F ₄ ].

Example of ^{biphenyl-2,2,,} 6-triyltris (diphenylphosphine) The vacuum was done in a Schlenk tube oven dried before filling with argon. Potassium acetate (1.60 mmol, 0.16 g, 3.2 eq), 2,2'- diiodo-6-bromobiphenyl (0.5 mmol, 0.24 g, 1 eq.) or one of its positional isomers (eg 2,6-diiodo-2'-bromophenyl) and diphenylphosphine ( 1.60 mmol, 0.28 mL, 3.2 eq.) Was added to a solution of N, N-dimethylacetamide or DMA (4.50 mL) followed by a solution of N, N-dimethylacetamide (0, 50 mL) containing palladium acetate (0.75 mg, 2 mol%). The solution turned red and immediately placed in an oil bath at 130 ° C. After 3 hours, the reaction mixture was allowed to reach room temperature. Water (20 mL) was added and the aqueous phase was extracted with dichloromethane (3 x 20.0 mL). The combined organic layers were dried over sodium sulfate. Evaporation of the solvent followed by chromatography on silica gel with cyclohexane / ethyl acetate (19: 1) led to biphenyl-2,2 ', 6-triyltris (diphenylphosphine) (0.45 mmol, 0.32 g, 91%) as a white solid (mp 219-221 ° C). 1 H NMR (CDCl ₃ , 300 MHz): δ = 7.36 (m, 5H), 7.24 (8H), 7.08

-7.17 (m, 14H), 7.01 (td, J = 5.92, 0.93 Hz, 5H), 6.90 (d, J = 7.79 Hz, 2);

H), 6.73 (t, J = 6.36 Hz, 4H), 6.69-6.63 (m, 1H), 6.04-6.00 (m, 1H).

¹³ C NMR (75 MHz, CDCI ₃ ): δ = 152.0 (td, J = 61.8, 6.3 Hz, 1 C),

146.2 (dt, J = 31.8, 6.6 Hz, 1 C), 139-138 (m, 4 C), 137.8, 137.6, 137.5- 137.0 (m, 2). C), 136.3 (dt, J = 8.8, 1.5 Hz, 1 C), 135.1 (d, J = 2.4 Hz, 1 C),

134.6 (2 C), 134.5-134.0 (m, 8 C), 133.5-133.0 (m, 3 C), 132.0 (m, 1 C),

129-128 (m, 21 C), 127.5,

³¹ P NMR (161 MHz, CDCI ₃ ): δ = -12.5 (d, J = 23.09 Hz, 2 P), -

14.6 (td, J = 23.36 Hz, 1 P).

 HRMS for C48H37P3 [M + H]: calculated value: 707.7381; Found value: 707.2139,

Example with (6,6'-dichlorobiphenyl-2,2'-diyl) bis (diphenylphosphine)

The vacuum was made in an oven-dried Schlenk tube before filling it with argon. Potassium acetate (0.66 mmol, 0.07 g, 2.2 eq.), 2-bromo-2 ', 6-dichloro-6'-iodobiphenyl (0.30 mmol, 0.14 g. , 1 eq.) And diphenylphosphine (0.66 mmol, 0.11 mL, 2.2 eq.) Were added to a solution of A, N-dimethylacetamide or DMA (3.00 mL) followed by solution of N, N-dimethylacetamide (0.30 mL) containing palladium acetate (0.45 mg, 2 mol %). The solution turned red and immediately placed in an oil bath at 130 ° C. After 3 hours, the reaction mixture was allowed to reach room temperature. Water (12.0 mL) was added and the aqueous phase was extracted with dichloromethane (3 x 15.0 mL). The combined organic layers were dried over sodium sulfate. Evaporation of the solvent followed by chromatography on silica gel with cyclohexane / ethyl acetate (19: 1) led to (6,6'-dichlorobiphenyl-2,2'-diyl) bis (diphenylphosphine) (0.24 mmol, 0.14 g, 80%) as a white powder (mp 205 ° -207 ° C.). 1H NMR (300 MHz, CDC1 _3): δ = 7.33 (m, 1H), 7.32 (m, 4H),

7.30-7.20 (m, 17H), 7.18 (m, 1H), 7.15 (m, 1H), 7.13 (m, 1H), 6.89 (m, 1H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 142.8 (t, J = 19.3 Hz, 2 C), 140.7 (d, J = 4.5 Hz), 140.7 (d, J = 4.5 Hz), 137.5 (m, 2 C), 135.7 (t, J = 5.4 Hz, 2 C), 135.5 (t, J = 5.3 Hz, 2 C). ), 134.8 (t, J = 11.1 Hz, 4 C), 133.1

(t, J = 10.3 Hz, 4 C), 132.9 (2 C), 129.8 (2 C), 129.3 (2 C), 128.9 (2 C), 128.4- 128.1 (m, 10 C).

³¹ P NMR (CDCl ₃ , 161 MHz): -11.95 (s). Example with (6'-methoxybiphenyl-2,2 ', 6-triyl) tris (diphenylphosphine)

The vacuum was made in an oven-dried Schlenk tube before filling it with argon. Potassium acetate (0.96 mmol, 0.10 g, 3.2 eq.), 2-bromo-2 ', 6-diiodo-6'-methoxybiphenyl (0.30 mmol, 0.17 g. , 1 eq.) And diphenylphosphine (0.96 mmol, 0.16 mL, 3.2 eq.) Were added to a solution of A, N-dimethylacetamide or DMA (3.00 mL) followed by solution of N, N-dimethylacetamide (0.30 mL) containing palladium acetate (0.45 mg, 2 mol%). The solution turned red and immediately placed in an oil bath at 130 ° C. After 3 hours, the reaction mixture was allowed to reach room temperature. Water (12 mL) was added and the aqueous phase was extracted with dichloromethane (3 x 15.0 mL). The combined organic layers were dried over sodium sulfate. Evaporation of the solvent followed by chromatography on silica gel with cyclohexane / ethyl acetate (19: 1) gave (6'-methoxybiphenyl-2,2 ', 6-triyl) tris (diphenylphosphine) sought (0.20 mmol, 0.15 g, 67%) as a pale brown solid (decomposition temperature: 210 ° C).

1H NMR (300 MHz, CDCI ₃ ): δ = 7.41 (td, J = 7.7, 2.5 Hz, 4H), 7.72-7.19 (m, 8H), 7.17; - 7.04 (m, 18H), 6.75 (m, 5H), 6.31 (d, J = 8.0)

Hz, 1H), 2.35 (s, 3H).

¹³ C NMR (75 MHz, CDC1 _3): δ = 139.2 (d, J = 5.3 Hz), 139.1, 138.9 (m, 4C), 137.8 (d, J = 13 , 9 Hz, 3 C), 137.43-137.33 (m, 1 C), 137.1- 136.9 (m, 2 C), 135.2 (s, 2 C), 134.6, 134.5, 134.3, 134.1 (t, J = 1.7 Hz, 2 C), 133.9 (t, J = 2.0 Hz, 2 C), 133.0, 132.9, 132.8, 129.1, 128.2-

128.0 (m, 13 C), 127.7-127.6 (m, 5 C), 127.5 (2 C), 126.9 (d, J = 2.3 Hz, 1 C), 109 , 5, 52.8,

³¹ P NMR (CDCl ₃ , 161 MHz): -12.6 (d, J = 23.1 Hz, 2 P), -14.8 (t, J = 23.4 Hz, 1 P).

HRMS for C ₄₉ H ₃₉ OP ₃ [M + H]: calculated value: 736.2287; Found value: 736.2234

The results obtained are given in the tables of FIGS. 1 to 3.

The process according to the invention is an extremely efficient catalyst system, which allows direct and rapid access to bis (arylphosphino) biphenyls in a single step, with excellent yields. Moreover, this process almost completely avoids the formation of phosphafluoroenes. When R 3 = H, N (CH ₃ ) ₂ , OCH ₂ O or OCF ₃ , phosphafluoroenes are a minor product that can be easily separated from the desired compound. In addition, this reaction is perfectly reproducible and allows the preparation of several grams of ligands. Finally this compound does not require the implementation of additional ligand.

 This method can be used for symmetrical or non-symmetrical compounds and is not substrate-dependent.

The subject of the present invention is also the use of a di or triphosphine compound as ligand for the formation, with one or more metals exhibiting a catalytic activity, of a catalytic complex, in particular for asymmetric hydrogenation and the formation of bonds. interatomic, in particular coupling CC, CN, C-0 and CP, said compounds being in particular selected from the group comprising. Examples of uses of the compounds according to the invention in catalysis:

By way of nonlimiting examples, mention may be made of methods for synthesizing BINAP type ligands described in:

- Miyashita, A .; Yasuda, A .; Takaya, H .; Toriumi, K .; Ito, T .; Souchi, T .; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932; Cai, D .; Payack, j. F .; Bender, D. R .; Hughes, D. L .; Verhoeven, T. R .; Reider, P. j. J. Org. Chem. 1994, 59, 7180; Ager, D.J .; East, M. B .; Eisenstadt, A .; Laneman, S. A. Chem. Common. 1997, 2359; and especially the following patent documents: EP 0 135 392, US 252 306, US 5 399 771, US 5 902 904, WO 99/36397,

Methods for synthesizing biphenyl ligands are described, for example in:

- Schmid, R .; Cereghetti, M .; Heiser, B .; Schoenholzer, P .; Hansen, H. Helv. Chim. Acta 1988, 71, 897,

 - Svensson, G .; Albertsson, j .; Frejd, T .; Klingstedt Acta Crystallograph. 1986, C42, 1324,

 - Miyashita, A .; Karino, H .; Shimamura, J.-L; Chiba, T .; Nagano, K .; Nohira, H .; Takaya, H. Chem. Lett. 1989, 1849,

 - Chiba, T .; Miyashita, A .; Nohira, H .; Takaya, H. Tetrahedron Lett. 1991, 32, 4745,

 - Henschke, J. P .; Zanotti-Gerosa, A .; Moran, P .; Harrison, P .; Mullen

B .; Casy, G .; Lennon, I. C. Tetrahedron Lett. 2003, 44, 4379,

 - Yamamoto, N .; Murata, M .; Morimoto, T .; Achiwa, K. Chem. Pharm. Bull. 1991, 39, 1085,

 - Murata, M .; Yamamoto, N .; Yoshikawa, K .; Morimoto, T .; Achiwa, K. Chem. Pharm. Bull. 1991, 39, 2767

 - Murata, M .; Morimoto, T .; Achiwa, K. Synlett 1991, 827,

 - Zhang, X .; Mashima, K .; Koyano, K .; Sayo, N .; Kumobayashi, H .; Akutagawa, S .; Takaya, H. Tetrahedron Lett. 1991, 32, 7283,

- Zhang, X .; Mashima, K .; Koyano, K .; Sayo, N .; Kumobayashi, H .; Akutagawa, S .; Takaya, HJ Chem. Soc, Perkin Trans. 1994, 2309, - Henschke, JP; Burk, MJ; Malan, CG; Herzberg, D .; Peterson, JA; Wildsmith, AJ; Cobley, CJ; Casy, G. Adv. Synth. Catal. 2003, 345, 300,

- Shibata, T .; Tsuruta, H .; Danjo, H .; Imamoto, T. J. Mol. Cat. A: Chemical 2003, 196, 117,

 - Schmid, R .; Foricher, J .; Cereghetti, M .; Schoenholzer, P. Helv. Chim. Acta 1991, 74, 370,

 - Chapuis, C; Barthe, M .; Laumer, J.-Y. S. Helv. Chim. Acta 2001, 84,

230

 - Tang, W .; Chi, Y .; Zhang, X. Org. Lett. 2002, 4, 1695,

 - Wu, S .; He, M .; Zhang, X. Tetrahedron: Asymmetry. 2004, 15, 2177; and the following patent documents: EP 104 375, EP 025 663,

EP 850 945, WO 01/21625, JP 04 210 696, JP 67 679, EP 479 542, WO 01/94359, EPI 186609, WO 02/12253, WO2002 / 040491,

 Uses of ligands of this family are described in:

F. Leroux, H. Mettler, v. Synth. Catal. 2007, 349, 323;

 - Michaud, G .; Bulliard, M .; Ricard, L .; Genet, J.-P .; Marinetti, A. Chem. Eur. J. 2002, 8, 3327,

Finally, the use of ligands bearing a methylenedioxo group in catalysis is described in:

- CC. Pai et al. Tetrahedron Lett. 2002, 43, 2789;

 - Leroux, F .; Gorecka, J .; Schlosser, M. Synthesis 2004, 326;

 - Jeulin, S .; Duprat de Paule, S .; Ratovelomanana-Vidal, V .; Genet, J.-P .; Champion, N .; Dellis, P. Angew. Chem. Int. Ed. 2004, 43, 320;

 - Jeulin, S .; De Paule, S. D .; Ratovelomanana-Vidal, V .; Genet, J.-P .; Champion, N .; Dellis, P. PNAS 2004, 101, 5799; and in particular in the following patent documents: WO 2005/049545, EP 926 152, EP 945 457 and EP 955 303.

Of course, the invention is not limited to the embodiment described and shown in the appended examples. Modifications remain possible, particularly from the point of view of the constitution of the various elements or by substitution technical equivalents, without departing from the scope of the invention.

Claims

1) Process for double or triple catalytic phosphination, essentially carried out in a single step of introducing phosphine groups onto a di, tri or tetrahalobiaryl compound, characterized in that it consists essentially of:  contacting said di, tri or tetrahalobiaryl compound with at least one molar equivalent of phosphine groups per halogen atom to be substituted on said halogenated compound, preferably with a molar excess of at least 10%,  in the presence of an effective amount of a Pd-based catalyst and a base and in the absence of any additional ligand,  - all in a solvent at a temperature of at least 100 ° C,  said di, tri or tetrahalobiaryl compound used being chosen from the group formed by di, tri or tetrahalobiphenyl of the respective formulas I, II or III and the dihalobinaphthyl of the following formula IV:

in which R ¹ represents Br or I, R ² represents Br or I, and R ³ is H, F, Cl, Br, I, Z, OZ, NR'R ", an aryl group or a substituted aryl group or polysubstituted, Z represents a saturated linear or branched alkyl group in Ci to C _6, optionally substituted , an optionally substituted C ₃ to C ₁₀ saturated cycloalkyl group, a saturated C ₁ to C ₆ perfluoroalkyl group, R 'and R "being independently selected from the group consisting of a hydrogen atom, a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, an optionally substituted C ₃ -C ₁₀ saturated cycloalkyl group,  R representing H, Cl or Br,

wherein R ¹ , R ² and R ⁴ have the meanings given for formula I, and wherein the substituent R ³ is selected from the group consisting of saturated chains: (CH ₂ ) _n , n being an integer from 3 to 6 (inclusive), 0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

wherein R ¹ and R ² have the meanings given for formula I, and wherein the substituents R ³ and R ⁴ are independently selected from the group consisting of saturated chains: (CH ₂ ) _n , n being an integer from 3 to 6 (inclusive), 0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

in which R, R and R have the meanings given for formula I and R ⁵ , identical to or different from R ³ , has the same definitions as R ³ . 2) Process according to claim 1, characterized in that said di, tri or tetrahalobiaryl compound used is chosen from the group formed by:  a) compounds of formula I in which: R ¹ represents Br or I, R ² represents Br or I, and R ³ represents H, F, Cl, Br, I, CH ₃ , OCH ₃ , N (CH ₃ ) ₂ , OCF ₃ , or Ph, R ⁴ representing H, or R ⁴ representing Cl when R ³ = C1, R ^{1 =} Br and R ² = I or, R ⁴ representing Br when R ³ = H ₃ CO and R ^{1 =} R ² = I, b) compounds of formula II in which: R ¹ , R ² and R ⁴ have the meanings given for formula I, and R ³ is selected from the group consisting of saturated chains O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O, c) compounds of formula III in which: R ¹ and R ² have the meanings given for formula I, and R ³ and R ⁴ are independently selected from the group consisting of saturated O-CH ₂ -O, O-CF ₂ -O or O- (CF ₂ ) ₂ -O chains. 3) Process according to claim 1 or 2, characterized in that one uses a di, tri or tetrahalobiaryl compound which contains at least one iodine atom per molecule. 4) Process according to claim 1 or 2, characterized in that a compound of formula I, II, III or IV is used in which R ^{1 =} R ² , preferably R = R ² = I. 5) Process according to claim 4, characterized in that the formula I or III of the compound used further verifies R ³ = R ⁴ or R ³ = R ⁴ . 6) Process according to any one of claims 1 to 5, characterized in that the necessary phosphine groups are provided by means of a compound of formula HP (R '") ₂ in which R'" is an alkyl group saturated linear or branched C l -C _6, optionally substituted cycloalkyl saturated C ₅ -C ₁₀ optionally substituted aryl, optionally substituted by one or more substituents selected from the group consisting of a halogen, a nitro group , amino, saturated linear or branched Ci -C ₆ alkoxy linear or branched saturated C l -C _6, or dialkylamino saturated linear or branched Ci to C ₆ R '"is preferably Ph or cyclohexyl group. 7 Process according to one of Claims 1 to 6, characterized in that a catalyst consisting of a mixture of Pd (OAc) ₂ and KOAc is used, with a catalyst content of at least 2% molar to the reaction mixture and a KOAc content of at least 2 molar equivalents. 8) Process according to any one of claims 1 to 7, characterized in that a solvent consisting essentially of DMA (N, N-dimethylacetamide) is used, that is to say at least 99% by weight. mass of pure DMA. 9) Process according to any one of claims 1 to 8, characterized in that the reaction temperature is chosen to be between 120 ° C and 150 ° C measured at atmospheric pressure. 10) Process according to any one of claims 1 to 9, characterized in that the reaction time is chosen to be between 30 minutes and 3 hours, preferably equal to 2 hours. 11) Use of a di, tri or tetrahalobiaryl compound for carrying out the process according to any one of Claims 1 to 10, characterized in that it is chosen from the group formed by di, tri or tetrahalobiphenyl of respective formulas I, II or III and the dihalobinaphthyl of formula IV as follows:

in which R represents Br or I, R ² represents Br or I, and R ³ is H, F, Cl, Br, I, Z, OZ, NR'R ", an aryl group or a substituted aryl group or polysubstituted, Z represents a saturated linear or branched alkyl group in Ci to C _6, optionally substituted , an optionally substituted C ₃ to C ₁₀ saturated cycloalkyl group, a saturated C ₁ to C ₆ perfluoroalkyl group, R 'and R "being independently selected from the group consisting of a linear saturated alkyl or branched C l -C _6, optionally substituted cycloalkyl saturated C ₃ to Cio, optionally substituted, R ⁴ representing H, Cl or Br,

wherein R ¹ , R ² and R ⁴ have the meanings given for formula I, and wherein the substituent R ³ is selected from the group consisting of saturated chains: (CH ₂ ) _n , n being an integer from 3 to 6 (inclusive), 0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

wherein R ¹ and R ² have the meanings given for formula I, and wherein the substituents R ³ and R ⁴ are independently selected from the group consisting of saturated chains: (CH ₂ ) _n , n being an integer from 3 to 6 (inclusive), 0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive),

in which R ¹ , R ² and R ³ have the meanings given for formula I and R ⁵ , identical or different from R ³ , has the same definitions as R ³ . 12) Use according to claim 11 characterized in that the di, tri or tetrahalobiaryl compound of formula I, II, III or IV satisfies R ^{1 =} R ² , preferably R ^{1 =} R ² = I. 13) Use according to claim 14, characterized in that the formula I or III further satisfies R ³ = R ⁴ or R ³ = R ⁴ . 14) Diphosphinated biaryl compounds corresponding to formula (la)

in which R ³ represents H, F, Cl, Br, I, Z, OZ, NR'R ", phenyl (Ph), or a substituted or polysubstituted Ph group, Z representing a linear or branched C1 to C saturated alkyl group; ₆ , optionally substituted, an optionally substituted C ₃ to C ₁₀ saturated cycloalkyl group, a saturated C ₁ to C ₆ perfluoroalkyl group, R 'and R "being independently selected from the group consisting of a hydrogen atom, a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, a saturated cycloalkyl group, C ₃ -C, optionally substituted, R ⁴ representing H, Cl or Br, provided that R ³ and R ⁴ are not simultaneously H, if R ³ is H then R ⁴ is not Cl and if R ³ is Z or OZ then R ⁴ is not H. 15) Compounds of formula (Ha)

in which R ⁴ has the meanings given for formula la and R ³ is in the group formed by saturated chains: (CH ₂ ) _n , n being an integer from 3 to 6 (inclusive), 0- (CF ₂ ) _p -O, p being an integer of 1 to 4 (inclusive), provided that if R ⁴ is H then R ³ is not - (CH ₂ ) ₄ - 16) Compounds of formula (IIIa)

(nie) wherein R ³ and R ⁴ are selected from the group consisting of saturated chains: (CH ₂ ) _n , n being an integer from 3 to 6 (inclusive), 0- (CH ₂ ) _m -0, where m is an integer from 1 to 4 (inclusive), 0- (CF ₂ ) _p -0, where p is an integer from 1 to 4 (inclusive) ,. 17) Compounds of formula (IVa)

in which R ³ and R ⁵ , which are identical or different, each represent H, F, Cl, Br, I, Z, OZ, NR'R ", phenyl (Ph), or a substituted or polysubstituted Ph group, Z representing an alkyl group saturated linear or branched C l -C _6, optionally substituted cycloalkyl saturated C ₃ to Cio, optionally substituted, saturated perfluoroalkyl group to C _6, R 'and R "being independently selected from the group consisting of a hydrogen atom, a saturated linear or branched alkyl group in Ci to C _6, optionally substituted, a saturated cycloalkyl group, C ₃ -C, optionally substituted, provided that R ³ and R ⁵ are not simultaneously H or OCH ₃ . 18) Compounds according to any one of claims 14 to 16, characterized in that they are chosen from the group comprising:  - (6- (Fluoro) biphenyl-2,2'-diyl) bis (diphenylphosphine) - (6-chlorobiphenyl-2,2'-diyl) bis (diphenylphosphine) (6-methylbiphenyl-2,2'-diyl) bis (diphenylphosphine):  2 ', 6-bis (diphenylphosphino) -N, N-dimethylbiphenyl-2-amine  - (6- (trifluoromethoxy) biphenyl-2,2'-diyl) bisdiphenylphosphine  2,2'-bisdiphenylphosphino-6-phenylbiphenyl  2- (5 - (Diphenylphosphino) benzo [d] [1,3] dioxo-4-yl) phenyl) diphenylphosphine - (2- (5- (diphenylphosphino) -2,2-difluorobenzo [(i]] , 3] dioxol-4-yl) phenyl) diphenylphosphine  - (2- (6- (Diphenylphosphino) -2,2,3,3-tetrafluoro-2,3-dihydrobenzo [b] [1,4] dioxin-5-yl) phenyl) diphenylphosphine  6'-methoxybiphenyl-2,2 ', 6-triyl) tris (diphenylphosphine) 19) Use of a di or triphosphine compound according to any one of claims 14 to 18 as a ligand for the formation, with one or more metals having a catalytic activity, of a catalytic complex, in particular for the asymmetric hydrogenation and the formation of interatomic bonds, in particular CC, CN, C-0 and CP couplings, said compounds being chosen from  - (6- (Fluoro) biphenyl-2,2'-diyl) bis (diphenylphosphine)  - (6-chlorobiphenyl-2,2'-diyl) bis (diphenylphosphine) (6-methylbiphenyl-2,2'-diyl) bis (diphenylphosphine):  2 ', 6-bis (diphenylphosphino) -N, N-dimethylbiphenyl-2-amine  - (6- (trifluoromethoxy) biphenyl-2,2'-diyl) bisdiphenylphosphine  2,2'-bisdiphenylphosphino-6-phenylbiphenyl  2- (5 - (Diphenylphosphino) benzo [d] [1,3] dioxo-4-yl) phenyl) diphenylphosphine - (2- (5- (diphenylphosphino) -2,2-difluorobenzo [(i]] , 3] dioxol-4-yl) phenyl) diphenylphosphine  - (2- (6- (Diphenylphosphino) -2,2,3,3-tetrafluoro-2,3-dihydrobenzo [b] [1,4] dioxin-5-yl) phenyl) diphenylphosphine  6'-methoxybiphenyl-2,2 ', 6-triyl) tris (diphenylphosphine).