BR112012024952B1 - PROCESS FOR THE CONVERSION OF A TERTIARY PHOSPHINE OXIDE, AND, USE OF TERTIARY PHOSPHINE - Google Patents

Abstract

“PROCESS FOR THE CONVERSION OF A TERTIARY Phosphine Oxide, AND, USE OF A TERTIARY Phosphine” A process for the conversion of a tertiary phosphine oxide to the corresponding tertiary phosphine comprising reacting this tertiary phosphine oxide with a reducing tertiary phosphine, in the presence of a catalyst that catalyzes the conversion.

Description

Technical field

The present invention relates to a process for producing tertiary phosphines. More particularly, the invention relates to a process for producing a tertiary phosphine by reducing the corresponding tertiary phosphine oxide.

Technical fundamentals

Phosphines, the phosphorus analogues of organic amines, constitute a class of highly important compounds with widespread industrial applicability within numerous areas. Tertiary phosphines are involved in a variety of widely used chemical reactions, for example, the Wittig reaction, ie the conversion of a ketone or aldehyde functionality to an olefinic link, the Mitsunobu reaction for stereo-specific preparations of CO, CN, C- S, or CC from alcohol functionalities, the Staudinger reaction, i. and. the conversion of azides to free amides, or the Apple reaction for the stereo-specific transformation of alcohols into halides. Additionally, phosphines are used as binders in homogeneous catalysis.

Tertiary phosphines are commonly prepared by reducing corresponding phosphine oxides. Over the years, concurrently with the understanding that tertiary phosphines are highly versatile compounds and useful for various applications, numerous different processes have been developed for the preparation of these organophosphate agents. However, virtually all chemical processes for preparing tertiary phosphines suffer from one or more disadvantages, related, for example, to cost, handling of reagents, high reaction temperature ranges, strict purification requirements, or significant influence on the environment, as well as the inherent complexity of the reaction system. Polymeric triphenyl phosphine analogs, inter alia, have been reported as a means to mitigate the problem with purification, allowing for simple filtration-based removal of the unwanted product from a specific chemical reaction. However, despite being an elegant solution to the purification problem, the problems associated with the high cost of reagents and the substantial water requirements diminish the usefulness of this strategy.

An alternative approach to allegedly generating a relatively pure tertiary phosphine product, supposedly obtainable via an economically feasible route, is disclosed in US4113783, in which triphenylphosphine oxide is reacted with a dialkyl aluminum hydride followed by subsequent hydrolysis, with the purpose of obtaining the desired product. A similar approach is revealed in US4507504, in which the reducing agent is a boron trihalide / trialkyl aluminum compound, again providing an apparently inexpensive route to tertiary phosphines. Notwithstanding the disclosure of overtly cheap routes to tertiary phosphines, the environmental influence of essentially all of the prior art tertiary phosphine production reactions is very high, inter alia as a result of the use of aggressive reagents, high temperatures, and / or quantities substantial amounts of solvents. In addition, numerous teachings in the prior art refer to procedures with low susceptibility for industrial application, relatively often as a complication of lack of scalability, or as a result of the use of aggressive reagents, obstructing the development of a safe and environmentally feasible process.

Summary of the invention

Therefore, there is a significant need in the art for improved processes for converting tertiary phosphine oxides into corresponding tertiary phosphines, with desired characteristics such as, for example, price moderation, simplicity, scalability, ease of handling, and efficiency, as well as low influence environmental.

Bearing in mind the substantial disadvantages associated with the processes constituting the state of the art, an objective of the present invention is to overcome such difficulties and satisfy existing needs, by providing a cheap, simple, and highly efficient chemical process with minimal environmental influence.

According to a first aspect the present invention, therefore, relates to an optimized process for converting tertiary phosphine oxides into the corresponding tertiary phosphines, using a completely new approach to the reduction of phosphine oxide.

Thus, the present invention relates to a process for converting a tertiary phosphine oxide to the corresponding tertiary phosphine, comprising reacting said tertiary phosphine oxide with a reducing tertiary phosphine, in the presence of a catalyst, in order to obtain the phosphine corresponding tertiary phosphate from tertiary phosphine oxide. In addition, the invention refers to numerous modalities related to said conversion process, as well as to the various uses for this highly efficient, simple, environmentally beneficial, and scalable process.

nas quais R1, R2 e R3 são cada um independentemente selecionados do grupo compreendendo hidrocarbila linear ou ramificada, substituída ou não substituída; e carbociclila ou heterociclila substituída ou não substituída;In one embodiment, the process according to the invention can be represented by the following reaction scheme, in which a tertiary phosphine of formula (I) is reduced to the corresponding tertiary phosphine of formula (III) by reaction with a reducing tertiary phosphine ( II) in the presence of a catalyst:

in which R1, R2 and R3 are each independently selected from the group comprising straight or branched, substituted or unsubstituted hydrocarbyl; and substituted or unsubstituted carbocyclyl or heterocyclyl;

A is a linking group; m is an integer from 0 to 2; R4, R5 and R6 are each independently selected from the group comprising straight or branched, substituted or unsubstituted hydrocarbyl; and substituted or unsubstituted carbocyclyl or heterocyclyl; B is a linking group; and n is an integer from 0 to 2.

The process of the present invention can be used very advantageously to reduce any tertiary phosphine oxide to the corresponding tertiary phosphine.

In addition, either the tertiary phosphine oxide to be reduced or the reducing tertiary phosphine can be bonded (a) on a solid support. In the first case, the process can be used for in situ generation of a tertiary phosphine from the corresponding tertiary phosphine oxide.

Thus, the present invention also provides a method of reducing a tertiary phosphine oxide bound to a solid support by contacting said tertiary phosphine oxide with a reducing tertiary phosphine in the presence of a catalyst for the reaction.

In one aspect, the present invention relates to the use of a tertiary phosphine to reduce a tertiary phosphine oxide, by reacting tertiary phosphine oxide with tertiary phosphine in the presence of a catalyst.

Tertiary phosphine to be used as a reducing agent can be attached to a solid support. Thus, the present invention also provides a method of reducing a tertiary phosphine oxide by contacting said tertiary phosphine oxide with a reducing tertiary phosphine bound on a solid support, in the presence of a catalyst.

Other aspects of the invention and its modalities will be evident from the following detailed description and the attached claims.

Detailed description of the invention

Some terms used with respect to the present invention will first be defined. Hydrocarbyl The term "hydrocarbyl" as used herein refers to a group consisting exclusively of carbon and hydrogen atoms. As defined herein, the hydrocarbyl group is branched or linear and is aliphatic. The hydrocarbyl group may contain one or more unsaturations, i.e. one or more double bonds or one or more triple bonds, or both. The group may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, such as 1 to 10 carbon atoms or 1 to 6 carbon atoms.

A substituted hydrocarbyl can carry one or more independently selected substituents and any substituent that does not interfere with the reduction reaction is considered to be possible for the purpose of the present invention. It is considered that the person with common experience in the art will be able to verify the suitability of a substituent without undue difficulty. For example, any substituent can be independently selected from substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, halogen, hydroxyl, thio, alkylthio, e.g. CIQ, cyano, halo-alkyl, etc. Carbocyclyl

The term "carbocyclyl" as used herein refers to a cyclic group consisting exclusively of carbon and hydrogen atoms. As defined herein, the carbocyclyl group can be aliphatic or aromatic and monocyclic or polycyclic, for example, bicyclic, tricyclic or tetracyclic, including fused or bridged cycles, as well as spirocycles. An aliphatic carbocyclyl can contain one or more unsaturations, i.e. one or more double bonds or one or more triple bonds, or both. The group may comprise 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms. For example, the hydrocarbyl group can be polycyclic and contain, for example, 10 to 20 carbon atoms or monocyclic and contain, for example, 3 to 8 carbon atoms. Examples of carbocyclyl are cyclopropyl, cyclo-butyl, cyclo-pentyl, cyclo-pentenyl, cyclo-pentadienyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, norbomyl, bicyclo [2.2.2] octyl, phenyl, naphthyl, fluorenila, azulenila, indanila, indenila, antrila etc.

A substituted carbocyclyl can bring one or several independently selected substituents and again it is considered that any substituent that does not interfere with the reduction reaction is possible, and that the person with ordinary experience in the art will be able to verify the suitability of the substitution without undue difficulty. , for example, following the general procedure described here for reducing tertiary phosphine oxide to the corresponding tertiary phosphine, and by usual analytical techniques to verify product identity and product yield. For example, any substituent can be independently selected from substituted or unsubstituted hydrocarbyl, carbocyclyl or heterocyclyl, halogen, hydroxyl, uncle, alkyl-thio, e.g. , cyan, halo-alkyl, etc. Heterocyclyl

The term "heterocyclyl" as used herein refers to a monocyclic or polycyclic radical, for example, bi-, tri- or tetracyclic radical having 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 ring atoms, at least one of which, for example, 1, 2, 3 or 4, such as 1 or 2, is a heteroatom selected from nitrogen, oxygen , phosphorus, silicon and sulfur, for example, nitrogen, oxygen and sulfur. The cyclic radical may contain one or more unsaturations, i.e. one or more double bonds or one or more triple bonds, or both. Examples of heterocyclyl are pyridyl, pyrrolyl, quinolinyl, furyl, thienyl, oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazolyl, triazolyl, tetrazolyl, tetrahydro-quinolinyl, tetrazolyl, thiadiazolyl, thiazolyl, triazol, triazol, zinc naphthyridinyl, imidazolyl, pyrimidinyl, phthalazinyl, indolyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrahydro-isoquinolinyl, pyrazinyl, indinol, pyridine, indolin, pyrininyl, pyridine, indolin quinolinyl, benzimidazolyl, benzodioxanil, benzodioxepinyl, benzodioxolyl, benzofuryl, benzothiazolyl, benzoxadiazolyl, benzothiazolyl, benzoxazinyl, benzoxazolyl, benzimidazolyl, benzomorpholinyl, benzyl, benzyl, benzyl, benzyl, benzyl, benzyl, benzazin aziridinyl, phenantrid inyl, azetidinyl, dihydro-pyranyl, dihydro-pyridyl, dihydro-pyrrolyl, dioxolanyl, dioxanil, dithianyl, dithiolanyl, imidazolidinyl, imidazolinyl, morpholinyl, oxetanyl, oxiranyl, pyrrolidinyl, piperiperidinyl, piperiperidinyl, piperiperidinyl, piperiperidinyl, piperiperolidinyl, piperiperolidinyl, piperiperidinyl, piperiperolidinyl pyranyl, pyrazolidinyl, quinuclidinyl, sulfalonyl, 3-sulfolenyl, tetrahydro-furyl, tetrahydro-pyranyl, tetrahydro-pyridyl, tietanyl, thyranil, thiolanil, thiomorpholinyl, trityanil, tropanil etc.

A substituted heterocyclyl can bring one or more independently selected substituents and again it is considered that any substituent that does not interfere with the reduction reaction is possible, and that the person with ordinary experience in the art will be able to verify the suitability of the substitution without undue difficulty. . For example, any substituent can be selected from substituted or unsubstituted hydrocarbyl, carbocyclyl or heterocyclyl, halogen, hydroxyl, thio, alkylthio, e.g. halo-alkyl, etc. Halogen

The terms "halogen" or "halo" etc., as used herein refer to F, Cl, Br and I. Alkyl The term "alkyl", as used herein, refers to a hydrocarbyl radical. In the case of alkyl being saturated, it is a radical according to the formula CnH2n.b and then it is referred to as "Cn alkyl". In addition, it should be understood that a group such as “C3-C2o-alkyl-Co-alkyl” or “C6-C20-alkyl-Co” represents a “C3-C20 cyclo-alkyl” and “C6-C20 aryl”, respectively .

As defined herein, the alkyl may also be unsaturated (i.e. alkenyl or alkynyl), in which case it may contain one or more double bonds or one or more triple bonds, or both. Aryl The term "aryl" as used herein includes reference to a carbocyclyl as defined herein which is aromatic. Aryl is often phenyl, but it can also be a polycyclic ring system, having two or more rings, for example, naphthyl, fluorenyl, azulenyl, anthryl, phenanthryl etc.

Hydrocarbilene, carbocyclylene, heterocyclylene, alkylene and arylene The terms "hydrocarbilen", "carbocyclylene", "heterocyclylene", "alkylene" and "arylene" as used herein, refer to the radicals derived from the corresponding hydrocarbon, carbocycle, heterocycle, alkane ( or alkene or alkaline, when unsaturated) or arene, and are essentially analogous to the monoradicals defined herein, except for being diradicals.

The present invention relates to a process for converting tertiary phosphine oxides into the corresponding tertiary phosphines, to the numerous modalities for said conversion, as well as to the various uses for this highly efficient, simple, environmentally beneficial, and scalable process.

The process comprises reacting a tertiary phosphine oxide, which is desirable to reduce to the corresponding phosphine, with a reducing tertiary phosphine, in the presence of a catalyst, which catalyzes the reduction of the tertiary phosphine oxide to be reduced. In the reaction, the reducing tertiary phosphine is oxidized to the corresponding tertiary phosphine oxide. The tertiary phosphine oxide and the tertiary phosphine product It should be understood that the process of the invention is not limited to any specific tertiary phosphine oxide and in fact, it is contemplated that any tertiary phosphine oxide can be reduced by the process of the invention, by a appropriate selection of the reducing tertiary phosphine.

The tertiary phosphine oxide of the invention can contain any number of phosphine oxide functions to be reduced. For example, tertiary phosphine oxide can contain 1 to 3, for example, 1 or 2 phosphine oxide functions. In one embodiment, the tertiary phosphine oxide contains 1 phosphine oxide function. In another embodiment, tertiary phosphine oxide contains 2 phosphine oxide functions.

na qual R1, R2 e R3 são cada um independentemente selecionados do grupo compreendendo hidrocarbila linear ou ramificada, substituída ou não substituída; e carbociclila ou heterociclila substituída ou não substituída; A é um grupo de ligação; e m é um número inteiro de 0 a 2.In addition, it is contemplated that phosphine oxide may additionally contain other functional groups. In one embodiment, tertiary phosphine oxide is a compound of formula (I)

in which R1, R2 and R3 are each independently selected from the group comprising straight or branched, substituted or unsubstituted hydrocarbyl; and substituted or unsubstituted carbocyclyl or heterocyclyl; A is a linking group; em is an integer from 0 to 2.

For example, each R1, R2 and R3 can be independently selected from the group comprising C1-C20 alkyl, C6-C2o aryl, C-C2o alkyl, C3-C2o-C0-C20 cycloalkyl, 5-20 membered heterocyclyl C0-C20 alkyl; 5-20 membered heteroaryl - C0-C2o alkyl where any alkyl, cycloalkyl and heterocyclyl group can be saturated or unsaturated, any alkyl group can be branched or linear, and any alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted with one or more substituents.

In one embodiment, in a compound of formula (I), any C1-C20 alkyl may be more especially a CpC10 alkyl; any C0-C20 alkyl can be more especially a Co-C10 alkyl; any C6-C20 aryl can be more especially a C6 -C4 aryl; any 5-20 membered heterocyclyl can be more especially a 5-14 membered heteroaryl; and any 5-20 membered heteroaryl may be more especially a 5-14 membered heteroaryl.

In one embodiment, in a compound of formula (I), any C 1 -C 20 alkyl may be more especially a C 1 -C 6 alkyl; any Co-C20 alkyl may be more especially a Co-C6 alkyl; any C0-C20 aryl can be more especially a C6-C10 aryl; any 5-20 membered heterocyclyl may be more especially a 5-10 membered heterocyclyl; and any 5-20 membered heteroaryl may be more especially a 5-10 membered heteroaryl.

For example, R1, R2 and R3 can each be independently selected from the group comprising C5-C2O heteroaryl C5-C2o-alkyl substituted or unsubstituted C6-C2θ-Cθ-C20 alkyl, for example, C5-C2o heteroaryl and aryl Substituted or unsubstituted Cg-C2o, such as phenyl, naphthyl and substituted or unsubstituted furyl, in particular substituted or unsubstituted phenyl.

More especially, R1, R2 and R3 can each be independently selected from the group comprising substituted or unsubstituted C6-C20-aryl CQ-C2O alkyl, for example, substituted or unsubstituted C6-C2o aryl, such as substituted phenyl or naphthyl or unsubstituted, in particular substituted or unsubstituted phenyl. In one embodiment, R1, R2 and R3 are all substituted or unsubstituted phenyl.

na qual R1, R2 e R3 são como definidos aqui acima.The integer m in formula (I) is an integer from 0 to 2, for example, 0 or 1. In one embodiment, m in formula (I) is 0, in which case the tertiary phosphine oxide of the invention can be represented by the formula (I ')

in which R1, R2 and R3 are as defined here above.

na qual R1, R2, R3 e A são como definidos aqui acima.In another embodiment, m in formula (I) is 1, and the tertiary phosphine oxide of the invention can then be represented by formula (I ”)

in which R1, R2, R3 and A are as defined here above.

In one embodiment, in a compound of formula (I), R1, R2 and R3 are all the same, for example, they are all substituted or unsubstituted phenyl.

Any reference made here to a compound of formula (I), should be understood as a reference also to a compound of formula (! ') Or (I ”), unless otherwise specified or evident from the context.

The bonding group A can be any diradical capable of bonding the two phosphorus atoms of the phosphine (oxide) functions to each other, by means of any number of interposed bonds. Linking group A may comprise substituted or unsubstituted hydrocarbilene or carbocyclylene or substituted or unsubstituted monocyclic or polycyclic heterocyclyl, and optionally one or more functional groups, such as ether or thioether function. When m in formula (I) is greater than 1, A is independently selected for each occurrence.

In one embodiment, A is a polycyclic diradical, such as a diradical comprising 2 to 8 ring groups, for example 2 to 6, or 2 to 4 ring groups, each ring group being independently selected from carbocycles and heterocycles of 5 or 6 members, saturated or unsaturated, aromatic or non-aromatic, and the ring groups are either fused to each other or linked to each other by means of one or more interconnected bonds of, for example, covalent or metallocene type, such as a covalent bond, an ether function, a thio-ether function, an optionally substituted alkylene group, for example, a methylene or ethylene group, or a ferrocene-type bond. In this embodiment, the two phosphine oxide functions are preferably linked in different ring groups.

In another embodiment, A may be a substituted or unsubstituted hydrocarbilene, carbocyclylene, or heterocyclylene. Linking group A can also be a substituted or unsubstituted metallocenylene, ie a diradical derived from a metallocene, ie a compound with the general formula (C5H5) 2M consisting of two cyclopentadienyl anions linked in a positively charged metal center ( M). As an example, A can be a substituted or unsubstituted ferrocenylene.

In one embodiment, A is a substituted or unsubstituted diradical selected from the group of CrC2o alkylene, C3-C20 substituted or unsubstituted, saturated or unsaturated, linear or branched, for example, CÔ-C20 arylene, 5-20 membered heterocyclyl , for example, 5-20 membered heteroarylene, C6-C40 bicyclylene, for example, C1-C40 biarylene, 10-40 membered bi-heterocyclyl, for example, 10-40 membered bi-heteroarylene, and C10-C3O ferrocenylene .

For example, A may be a substituted or unsubstituted diradical selected from the group of C6-C2θ arylene, 5-20 membered heterocyclylene, 5-20 membered heteroarylene, C1-240 biarylene, 10-40 membered bi- heterocyclyl, bi - 10-40 membered heteroarylene, and Cio-C3O ferrocenylene.

In one embodiment, A is a substituted or unsubstituted diradical selected from the group of C1-C4o biarylene, 5-20 membered heterocyclyl and C1-C3o ferrocenylene, for example, binaftyl, such as 2,2'-binaftyl; xanthene, for example, 4,5-xanthene; and ferrocenylene (Cio), for example, 1,1'-ferrocenylene.

Examples of tertiary phosphine oxides which can be reduced according to the invention are triphenyl phosphine oxide, 2,2'-bis (diphenyl-oxy-phosphine) -1,1 '-binaftyl, bis (2- (diphenyl- oxy-phosphism) -phenyl-ether, 9,9-dimethyl-4,6-bis (diphenyl-oxy-phosphine) -xanthene, 1,1'-bis (diphenyl-oxy-phosphine) - ferrocene, tris oxide ( 4-chloro-phenyl) -phosphine, bis (2-methyl-phenyl) -phenyl-phosphine oxide, bis (2-methyl-phenyl) -phenyl-phosphine oxide, or any of these compounds attached on a solid support and / or polymeric.

However, as noted above, the process of the invention can very advantageously be applied to essentially any tertiary phosphine oxide, and some examples of tertiary phosphines that can be prepared from the corresponding phosphine oxide by the reduction reaction according to the invention are: di- (tert-butyl) -phenyl-phosphine, di (1-methyl-butyl) -phenyl-phosphine, di (1,1-dimethyl-propyl) -phenyl-phosphine, di (1,1-dimethyl- butyl) -phenyl-phosphine, di- (tert-butyl) -2-methoxy-phenyl-phosphine, di (1-methyl-butyl) -2-methoxy-phenyl-phosphine, di (1,1-l-dimethyl-propyl) -2-methoxy-phenyl-phosphine, di (1,1-dimethyl-butyl) -2-methoxy-phenyl-phosphine, bis (trimethyl-silyl) -2-methoxy-phenyl-phosphine, di- (tert-butyl) - 4-methoxy-phenyl-phosphine, di (1-methyl-butyl) -4-methoxy-phenyl-phosphine, di (1,1-dimethyl-propyl) -4-methoxy-phenyl-phosphine, di (l, l -dimethyl-butyl) -4-methoxy-phenyl-phosphine, di- (tert-butyl) -2,4-dimethoxy-phenyl-phosphine, di (1-methyl-butyl) -2,4-dimethoxy-phenyl-phosphine , di (1,1-dimethyl-propyl) -2,4-dimethoxy-phenyl- phosphine, di (1,1-dimethyl-butyl) -2,4-dimethoxy-phenyl-phosphine, di- (tert-butyl) -2,4,6-trimethoxy-phenyl-phosphine, di (1-methyl-butyl ) -2,4,6-trimethoxy-phenyl-phosphine, di (1,1-dimethyl-propyl) -2,4,6-trimethoxy-phenyl-phosphine, di (1,1-dimethyl-butyl) -2, 4,6-tri-methoxy-phenyl-phosphine, di- (tert-butyl) -2-methyl-phenyl-phosphine, di (1-methyl-butyl) -2-methyl-phenyl-phosphine, di (l, l -dimethyl-propyl) -2-methyl-phenyl-phosphine, di (1,1-dimethyl-butyl) -2-methyl-phenyl-phosphine, di (tert-butyl) -4-methyl-phenyl-phosphine, di ( 1-methyl-butyl) -4-methyl-phenyl-phosphine, di (1,1-dimethyl-propyl) -4-methyl-phenyl-phosphine, di (1,1-dimethyl-butyl) -4-methyl-phenyl -phosphine, di- (tert-butyl) -2,4-dimethyl-phenyl-phosphine, di (1-methyl-butyl) -2,4-dimethyl-phenyl-phosphine, di (1,1-dimethyl-propyl) -2,4-dimethyl-phenyl-phosphine, di (1,1-dimethyl-butyl) -2,4-dimethyl-phenyl-phosphine, di- (tert-butyl) -2,4,6-trimethyl-phenyl- phosphine, di (1-methyl-butyl) -2,4,6-trimethyl-phenyl-phosphine, di (1,1-dimethyl-propyl) -2,4,6-tri-methyl-phenyl-phosphine, di ( 1,1-dimethyl-butyl) -2,4,6- tri-methyl-phenyl-phosphine, di- (tert-butyl) -pentafluoro-phenyl-phosphine, di (1-methyl-butyl) -pentafluoro-phenyl-phosphine, di (1,1-dimethyl-propyl) -pentafluoro- phenyl-phosphine, di (1,1-dimethyl-butyl) -pentafluoro-phenyl-phosphine, di- (tert-butyl) -2,4-difluoro-phenyl-phosphine, di (1-methyl-butyl) -2, 4-difluoro-phenyl-phosphine, di (1,1-dimethyl-propyl) -2,4-difluoro-phenyl-phosphine, di (1,1-dimethyl-butyl) -2,4-difluoro-phenyl-phosphine, di- (tert-butyl) -3,5-difluoro-phenyl-phosphine, di (1-methyl-butyl) -3,5-difluoro-phenyl-phosphine, di (1,1-dimethyl-propyl) -3, 5-difluoro-phenyl-phosphine, di (1,1-dimethyl-butyl) -3,5-difluoro-phenyl-phosphine, di (tert-butyl) -4-fluoro-phenyl-phosphine, di (1-methyl- butyl) -4-fluoro-phenyl-phosphine, di (1,1-dimethyl-propyl) -4-fluoro-phenyl-phosphine, di (1,1-dimethyl-butyl) -4-fluoro-phenyl-phosphine, di (1,2-dimethyl-butyl) -4-fluoro-phenyl-phosphine, di (tert-butyl) -4-chloro-phenyl-phosphine, di (1-methyl-butyl) -4-chloro-phenyl-phosphine, di (1,1-dimethyl-propyl) -4-chloro-phenyl-phosphine, di (1,1-dimethyl-butyl) -4-clo ro-phenyl-phosphine, di (tert-butyl) -4-bromo-phenyl-phosphine, di (1-methyl-butyl) -4-bromo-phenyl-phosphine, di (1,1-dimethyl-propyl) -4 -bromo-phenyl-phosphine, di (1,1-dimethyl-butyl) -4-bromo-phenyl-phosphine, di (tert-butyl) -4- (tert-butyl) -phenyl-phosphine, di (1-methyl -butyl) -4- (tert-butyl) -phenyl-phosphine, di (1,1-dimethyl-propyl) -4- (tert-butyl) -phenyl-phosphine, di (1,1-dimethyl-butyl) - 4- (tert-butyl) -phenyl-phosphine, bis (trimethyl-silyl) -4- (tert-butyl) -phenyl-phosphine, di (tert-butyl) -2,4,6-tri (tert-butyl) - phenyl-phosphine, di (1-methyl-butyl) -2,4,6-tri (tert-butyl) -phenyl-phosphine, di (1,1-dimethyl-propyl) -2,4,6-tri ( tert-butyl) -phenyl-phosphine, di (1,1-dimethyl-butyl) -2,4,6-tri (tert-butyl) -phenyl-phosphine, di- (tert-butyl) -4-trifluoro-methyl -phenyl-phosphine, di (1-methyl-butyl) -4-trifluoro-methyl-phenyl-phosphine di (1,1-dimethyl-propyl) -4-trifluoro-methyl-phenyl-phosphine, di (1,1 - dimethyl-butyl) -4-trifluoro-methyl-phenyl-phosphine, di- (tert-butyl) -3,5-bis (trifluoro-methyl) -phenyl-phosphine, di (1-methyl-butyl) -3,5 - bis (trifluoro-m ethyl) -phenyl-phosphine, di (1,1-dimethyl-propyl) -3,5-bis (trifluoro-methyl) -phenyl-phosphine, di (1,1-di-methyl-butyl) -3,5- bis (trifluoro-methyl) -phenyl-phosphine, di- (tert-butyl) -2-biphenyl-phosphine, di (1-methyl-butyl) -2-biphenyl-phosphine, di (1,1-dimethyl-pi ' opyl) -2-biphenyl-phosphine, di (1,1-dimethyl-butyl) -2-biphenyl-phosphine, di (1,2-dimethyl-butyl) -2-biphenyl-phosphine, bis (trimethyl-silyl) - 2-biphenyl-phosphine, di- (tert-butyl) -3-biphenyl-phosphine, di (1-methyl-butyl) -3-biphenyl-phosphine, di (1,1-dimethyl-propyl) -3-biphenyl- phosphine, di (1,1-dimethyl-butyl) -3-biphenyl-phosphine, di- (tert-butyl) -1-naphthyl-phosphine, di (1-methyl-butyl) -1-naphthyl-phosphine, di ( 1,1-dimethyl-propyl) -1-naphthyl-phosphine, di (1,1-dimethyl-butyl) -1-naphthyl-phosphine, di- (tert-butyl) -2- naphthyl-phosphine, di (1 - methyl-butyl) -2-naphthyl-phosphine, di (1,1-dimethyl-propyl) -2-naphthyl-phosphine, di (1,1-di-methyl-butyl) -2-naphthyl-phosphine, di- ( tert-butyl) -5-acenafty-phosphine, di (1-methyl-butyl) -5-acenafty-phosphine, di (1,1-dimethyl-propyl) -5-acenafty-phosphine, d i (1,1-dimethyl-butyl) -5-acenafty-phosphine, di- (tert-butyl) -9-fluorenyl-phosphine, di (l-methyl-butyl) -9-fluorenyl-phosphine, di (l, l-dimethyl-propyl) - 9-fluorenyl-phosphine, di (1,1-di-methyl-butyl) -9-fluorenyl-phosphine, di- (tert-butyl) -9-anthracenyl-phosphine, di (1 - methyl-butyl) -9-anthracenyl-phosphine, di (1,1-dimethyl-propyl) -9-anthracenyl-phosphine, di (1,1-di-methyl-butyl) -9-anthracenyl-phosphine, di- ( tert-butyl) -9-phenantryl-phosphine, di (1-methyl-butyl) -9-phenantryl-phosphine, di (1,1-dimethyl-propyl) -9-phenantryl-phosphine, di (1,1-dimethyl -butyl) -9-phenanthryl-phosphine, di- (tert-butyl) -1 -pyrenyl-phosphine, di (1-methyl-butyl) -1 -pyrenyl-phosphine, di (1,1 - dimethyl-propyl) - 1-pyrenyl-phosphine, di (1,1-di-methyl-butyl) -1-pyrenyl-phosphine, 1,2-bis (di-tert-butyl-phosphine) -benzene, 1,2-bis (di- 1-methyl-butyl-phosphino) -benzene, 1,2-bis [di (1,1-dimethyl-propyl) -phosphino] -benzene, 1,2-bis [bis (1,1-dimethyl-butyl) - phosphino] -benzene, 1,2-bis [bis (trimethyl-silyl) -methyl-phosphine) -benzene, 1,3-bis (di-tert-butyl-phosphine) -benzene, 1,3-bis [bis- (trimethyl-silyl-phosphino)] - benzene, 1,3-bis (di-1-methyl-butyl-phosphmo) -benzene, 1,3-bis- [di ( 1,1-di-methyl-propyl) -phosphino] -benzene, 1,3-bis [bis (1,1-dimethyl-butyl) -phosphino] -benzene, 1,3-bis- [bis (trimethyl-silyl ) -methyl-phosphino) -benzene, 1,4-bis (di-tert-butyl-phosphino) -benzene, 1,4-bis (di-1-methyl-butyl-phosphino) -benzene, 1,4-bis [di (1,1-dimethyl-propyl) -phosphino] -benzene, 1,4-bi s [bi s (1,1-dimethyl-butyl) -phosphino] -benzene, 1,4-bis [bis (trimethyl -silyl) -methyl-phosphine) -benzene. 1,4-bis (di-tert-butyl-phosphine) - cyclohexane, 1,4-bis (dimethyl-butyl-phosphine) -cyclohexane, 1,4-bis [di (1,1-di- methyl-propyl) -phosphine] -cyclohexane, 1,4-bis [bis (1,1-dimethyl-butyl) -phosphino] -cyclohexane, 1,4-bis [bis (trimethyl-silyl) -methyl -phosphino) -cyclohexane, 1,1'- bis (di-tert-butyl-phosphino) -ferrocene, 1,1'-bis (di-1-methyl-butyl-phosphino) - ferrocene, 1,1 ' -bis [di (1,1-dimethyl-propyl) -phosphino] -ferrocene, 1,1'-bis [bis (trimethyl-silyl) -methyl-phosphine) -ferrocene, 1,2-bis (di-tert- butylphosphino) - ferrocene, 1,2-bis (di-1-methyl-butyl-phosphino) -ferrocene, 1,2-bis [di (1,1-dimethyl-propyl) -phosphino] -ferrocene, l, 2-bis [bis (1,1-dimethyl-butyl) -phosphino] -ferrocene, 1,2-bis- [bis (trimethyl-silyl) -methyl-phosphine) -ferrocene, tri-tert-butyl-phosphine, trineopentyl -phosphine, tris (trimethyl-silyl) -phosphine, tri (1-methyl-butyl) -phosphine, tri (1-ethyl-propyl) -phosphine, tri (1,1-dimethyl-propyl) -phosphine, tris (1 , 2-dimethyl-propyl) -phosphine, tri (1-methyl-pentyl) -phosphine, tris (1,1-dimethyl-butyl) -phosphine, tris (1,2-dimethyl) yl-butyl) -phosphine, tris (1,3-dimethyl-butyl) -phosphine, tri (1-ethyl-butyl) -phosphine, tris (1,1,2-tri-methyl-propyl) -phosphine, tris ( 1,2,2-trimethyl-propyl) -phosphine, tri (1-ethyl-1-methyl-propyl) -phosphine, tris [(trimethyl-silyl) -methyl] -phosphine, tri (tert-butyl) -phosphine, trineopentyl-phosphine, 2,2'-bis [bis (3,5-dimethyl-phenyl) -phosphino] -1, l'-binaftyl, 2,2'-bis [bis (4-methoxy-phenyl) -phosphine] -l, l'-binaftyl, 2,2'-bis [bis (4-dimethyl-amino-phenyl) -phosphino] -1,1 '-binaftyl, 2,2'-bis [bis (4-fluoro-phenyl ) - phosphino] -l, l'-bi- naphthyl, 2,2'-bis [bis (3,5-di-tert-butyl-4-methoxy-phenyl) -phosphino] - 1,1 '-binaftyl, 2,2 '-bis (diphenyl-phosphine) -1,1' -binaftyl, 2,2 '-bis [bis (2-methyl-phenyl) -phosphine] -1,1' -bi-naphthyl, 2,2 '-bis [bis (3-methyl-phenyl) -phosphino] -1,1'- binaftyl, 2,2'-bis [bis (4-methyl-phenyl) -phosphine] -1,1'-binaftyl, 2 , 2'-bis [bis (4-tert-butyl-phenyl) -phosphino] -1, l'-bi-naphthyl, 2,2'-bis [bis (3,5-di-tert-butyl-phenyl) - phosphino] -1,1 '-binaftyl, 2,2'-bis [bis (4-methoxy-3,5-dimethyl-phenyl) -phosphine] -1, 1' - binafty a, 2,2'-bis [bis (4-chloro-phenyl) -phosphino] -1,1'-binaftyl, 2,2'-bis [bis (1,3-benzodioxol-5 -yl) -phosphine] -1,1 '-binaftyl, 2,2' -bis [bis (2-naphthyl) -phosphino] -1,1'-binaftyl, 2,2'-bis (diphenyl-phosphine) -6,6'-di -phenyl-l, l'-binaftyl, 2,2'-bis (diphenyl-phosphine) -7,7'-dimethoxy-1,1'-binaftyl, and any of these phosphines attached on a solid and / or polymeric support, for example, 4-diphenyl-phosphine-methyl in polystyrene resin, and JandaJel ™ triphenyl-phosphine (JandaJel ™ is a polystyrene resin available from Sigma-Aldrich Co.), and the like.

It is to be understood that the compounds of the invention may include one or more atoms having a form (R) and form (S), in which case all forms and combinations thereof are contemplated to be included within the scope of the invention, as well as any mixture of any isomers.

The reducing tertiary phosphine The reducing tertiary phosphine can contain one or more tertiary phosphine functions and the phosphorus atom of each phosphine function can be linked in selected groups of linear or branched, substituted or unsubstituted hydrocarbyl; and substituted or unsubstituted carbocyclyl or heterocyclyl, as defined herein above.

na qual R4, R5 e R6 são cada um independentemente selecionados do grupo compreendendo hidrocarbila linear ou ramificada, substituída ou não substituída; e carbociclila ou heterociclila substituída ou não substituída, alifática ou aromática; B é um grupo de ligação; e n é um número inteiro de 0 a 2, por exemplo, 0 ou 1.For example, the reducing tertiary phosphine may contain 1 to 3 phosphine functions. In one embodiment, the reducing tertiary phosphine contains 1 or 2 phosphine functions. In a special embodiment, the reducing tertiary phosphine contains 1 phosphine function. In addition, it is contemplated that the reducing tertiary phosphine may additionally contain other functional groups. In one embodiment, the reducing tertiary phosphine is represented by the formula (II)

in which R4, R5 and R6 are each independently selected from the group comprising straight or branched, substituted or unsubstituted hydrocarbyl; and substituted or unsubstituted, aliphatic or aromatic carbocyclyl or heterocyclyl; B is a linking group; and n is an integer from 0 to 2, for example, 0 or 1.

For example, R4, R5 and R6 can be selected from the group consisting of substituted or unsubstituted, linear or branched C1 -C2 hydrocarbyl, for example, C1C6 hydrocarbyl, for example, C1C6 hydrocarbyl; and substituted or unsubstituted, aliphatic or aromatic C3-C2o carbocyclyl, for example, C3-C10 carbocyclyl, or C3-C6 carbocyclyl, or 5-20 membered heterocyclyl, for example, 5-10 membered heterocyclyl, or 5-membered heterocyclyl -6 members.

In one embodiment, R4, R5 and R6 are independently selected from the group comprising substituted or unsubstituted, linear or branched CrC2o hydrocarbyl, for example, Q-C10 hydrocarbyl, for example, CrC6 hydrocarbyl; and substituted or unsubstituted, aliphatic C3-C20 carbocyclyl, for example, C3-C10 carbocyclyl, or C3-C6 carbocyclyl. For example, any hydrocarbyl group can be an alkyl and any carbocyclyl group can be a cycloalkyl. In one embodiment, R4, R5 and R6 are all the same, although they may also be equally different from each other.

na qual R4, R5 e R6 são como definidos aqui acima. Em outra modalidade, n em fórmula (II) é 1 ou 2.The number of phosphine functions in the compound of formula (II) can suitably vary from 1 to 3, ie the integer n in formula (II) is 0 to 2. In one embodiment, n in formula (II) is 0, in in which case the reducing tertiary phosphine of the invention can be represented by the formula (IF)

in which R4, R5 and R6 are as defined here above. In another embodiment, n in formula (II) is 1 or 2.

In one embodiment, in a compound of formula (II), R4, R5 and R6 are all the same, for example, they are all substituted or unsubstituted C1-6 alkyl or C3-C6 cycloalkyl.

The bonding group B can be any diradical capable of bonding the two phosphorus atoms of the phosphine (oxide) functions together, by means of any number of interposed bonds. The linking group B can comprise substituted or unsubstituted hydrocarbilene, monocyclic or polycyclic carbocyclylene or heterocyclyl, and optionally one or more functional groups, such as ether or thio-ether function.

When n in formula (II) is greater than 1, B is independently selected for each occurrence. In one embodiment, B is a polycyclic diradical, such as a diradical comprising 2 to 8 ring groups, for example 2 to 6, or 2 to 4 ring groups, each ring group being independently selected from carbocycles and heterocycles of 5 or 6 members, saturated or unsaturated, aromatic or non-aromatic, and the ring groups are either fused to each other or linked to each other by means of one or more interconnected bonds of, for example, covalent or metallocene type, such as a covalent bond, an ether function, a thio-ether function, an optionally substituted alkylene group, for example, a methylene or ethylene group, or a ferrocene-type bond. In this embodiment, the two phosphine oxide functions are preferably linked in different ring groups.

In another embodiment, B can be a substituted or unsubstituted hydrocarbilene, carbocyclylene, or heterocyclylene. The bonding group B can also be a substituted or unsubstituted metallocenylene, ie a diradical derived from a metallocene, ie a compound with the general formula (C5H5) 2M consisting of two cyclopentadienyl anions linked in a positively charged metal center ( M). As an example, B can be a substituted or unsubstituted ferrocenylene.

In one embodiment, B is a substituted or unsubstituted diradical selected from the group of C 1 -C 2 alkylene, C 3 -C 2 substituted or unsubstituted, saturated or unsaturated, linear or branched, for example, C 6 -C 2 arylene, 5- 20 members, for example, 5-20 membered heteroarylene, C6-C40 bicyclylene, for example, C12-C40 biarylene, 10-40 membered bi-heterocyclyl, for example, 10-40 membered bi-heteroarylene, and Cio ferrocenylene -C3O.

For example, B can be a substituted or unsubstituted diradical selected from the group of C6-C2o arylene, 5-20 membered heterocyclylene, 5-20 membered heteroarylene, C12-C40 biarylene, 10-40 membered bi- heterocyclyl, bi - 10-40 membered heteroarylene, and C10-C30 ferrocenylene.

In one embodiment, B is a substituted or unsubstituted diradical selected from the group of C12-C40 biarylene, 5-20 membered heterocyclylene and C10-C30 ferrocenylene, for example, binaftyl, such as 2,2'-binaftyl; xanthene, for example, 4,5-xanthene; and ferrocenylene (Ciθ), for example, 1,1'-ferrocenylene.

The basicity of the reducing tertiary phosphine is preferably greater than the basicity of the product phosphine. This is because a more basic phosphine is more easily oxidized than a less basic phosphine. However, the person of ordinary skill in the art will understand that the reaction according to the invention can be further conducted in the desired direction, for example, by adding an excess of the reducing tertiary phosphine to the reaction mixture.

As used herein, the term "basicity" essentially refers to the phosphine's ability to donate electron pairs, i.e. to act as a Lewis base; the electron pairs involved being those of phosphine phosphine.

The basicity of the reducing phosphine is mainly governed by the groups linked in the phosphine function (s), i.e. mainly the groups R4, R5 and R6 in the formula (II). For example, compounds of formula (II) in which R4, R5 and R6 are selected from C 1 -C 6 alkyl and C 3 -C 6 cycloalkyl, such as tri-tert-butyl-phosphine and tricyclo-propyl-phosphine, are quite basic compounds and as such they are advantageous as reducing tertiary phosphines for use in a process according to the invention.

Tertiary reducing phosphine, therefore, is preferably selected so as to be a stronger base than the tertiary phosphine oxide reaction product. Additional parameters for selecting tertiary reducing phosphine can be, for example, ease of handling, availability and low cost.

The oxidation product of the reducing tertiary phosphine is usually considered to be a by-product of the process. However, it should be understood that, if so desired, this oxidation product can also be collected and, for example, recycled through reduction or used in any other way.

Non-limiting examples of reducing tertiary phosphine suitable for the process of the present invention can be selected from the group comprising tributyl-phosphine, triethyl-phosphine, trimethyl-phosphine, tricyclohexyl-phosphine, tri-tert-butyl-phosphine, triphenyl-phosphine and other similar phosphines.

The reducing tertiary phosphine is preferably present in an amount of at least 1 molar equivalent of reducing tertiary phosphine phosphorus to the phosphine oxide phosphorus of the tertiary phosphine oxide. For example, the reducing tertiary phosphine may be suitably present in an amount such that the molar ratio of the reducing tertiary phosphine function (s) to the phosphine oxide function (s) of the tertiary phosphine oxide a to be reduced is about 1 to about 10, for example, about 1.2 to about 5, for example, about 1.5 to about 2.5, or about 2.

In one embodiment, the reducing tertiary phosphine is present in excess, compared to phosphine oxide. In this embodiment, the reducing tertiary phosphine can be adequately present in an amount such that the molar ratio of reducing phosphine function (s) to the reducing phosphine oxide (s) of the tertiary phosphine oxide to be reduced is from about 2 to about 10, for example, from about 3 to about 8, or about 4 to about 6.

In one embodiment, the reducing tertiary phosphine is attached to a solid support. In this embodiment, the reducing tertiary phosphine can be regenerated after use, for example, by reacting it with a reducing agent, such as a reducing tertiary phosphine, which may be more basic than the reducing tertiary phosphine bound in the solid phase or that is added in excess in the reaction medium containing the solid phase with the bound reducing phosphine to be regenerated. The catalyst

According to the invention, the catalyst can be any type of chemical species capable of catalyzing the reaction of the invention. Preferably, the catalyst comprises at least one halogen atom. The catalyst can inter alia be selected from the group comprising fluorine (F2), chlorine (Cl2), bromine (Br2), iodine (I2), for example, I2 and Br2; halo-alkanes, in particular tetrahalo-methanes, such as tetrachloromethane, tetrabromo-methane, tetraiodine-methane, tetrafluoro-methane, for example, CC14; phosphine dihalides, for example, tertiary phosphine dihalides, such as triphenyl phosphine dichloride, triphenyl phosphine dibromide, triphenyl phosphine diiodide, triphenyl phosphine difluoride, for example triphenyl phosphine dichloride , and / or any six trialkylated, cycloalkylated or arylated analogs.

The catalyst only needs to be present in catalytic amounts, but since undesirable water present in reagents and solvents can consume the catalyst, the optimum catalyst load can be, for example, 0.02-0.5 molar equivalent of the oxide of tertiary phosphine to be reduced, in particular 0.05-0.2 molar equivalent, for example, 0.08-0.12 molar equivalent and suitably approximately 0.1 molar equivalent. In fact, increasing the amount of catalyst above the indicated ranges does not appear to have any significant effect on the reaction. However, depending on the catalyst used, higher / lower molar equivalents may be relevant, and increasing / decreasing the amount of catalyst, therefore, is also within the scope of the present invention.

The catalyst can be present in any physical form, but suitable forms known to a person skilled in the art for a special combination of reagents and / or reaction conditions are naturally preferable.

Without the desire to link to any specific theory, it is assumed that the reaction mechanism of the process of the present invention depends on the initial interaction between the catalyst and the reducing tertiary phosphine, possibly leading to an intermediate complex formed between at least certain components of these two molecules. Subsequently, the tertiary phosphine oxide is reduced to its corresponding tertiary phosphine, a reaction facilitated by the intermediate complex generated from the catalyst and the reducing tertiary phosphine. Theoretically, the process of the present invention thus results, in total, in reduction of the tertiary phosphine oxide to the corresponding tertiary phosphine, oxidation of the reducing tertiary phosphine to the corresponding tertiary phosphine oxide, as well as regeneration of the catalyst. The reaction medium

The process of converting the tertiary phosphine oxide into the corresponding phosphine can be carried out under solvent-free conditions, with the purpose of further reducing the environmental influence of the process. The process of the present invention has, by virtue of the selection of reagents and the conditions under which the reaction is taking place, a remarkably low environmental influence, but the possibility to use solvent-free reaction conditions further optimizes the ecologically beneficial characteristics of the present invention. . However, the process can also be carried out in anhydrous aprotic solvent (s), such as, for example, toluene, hexane, tetrahydrofuran (THF), acetonitrile, diethyl ether, propionitrile, benzonitrile , ethyl acetate and mixtures thereof, for example, tetrahydrofuran, acetonitrile, diethyl ether, propionitrile, toluene, ethyl acetate and mixtures thereof. A preferred solvent for the process of the present invention can be selected from the group comprising acetonitrile and a 1 to 1 mixture of acetonitrile and THF.

The order of addition of the constituents of the reaction has no effect on the process, with the implication that obstacles associated with scaling and handling can be minimized. Furthermore, as a result of the advantageous features of the present invention, the process can be carried out in virtually any type of reaction vessel, further increasing the versatility, the specificity in an industrial perspective, of the invention.

The process of the present invention is, as mentioned above, associated with numerous advantages related to price modality, low environmental influence, scalability, and ease of handling. Other advantageous aspects of the invention relate, for example, to the fact that the process can be carried out at any temperature, more conveniently at room temperature, and that the concentration of the reaction mixture does not affect the process. In addition, the process is very mild and therefore highly suitable for sensitive reaction systems. For example, the process of the present invention is ideally suited for use in reducing tertiary phosphine oxides bonded to a support base or polymeric support (o), in order to regenerate the tertiary phosphine bonded to a support base or polymeric support ( O). For example, the process of the invention can be used in the regeneration of triphenylphosphine over polystyrene. Such uses, and additional uses to regenerate tertiary phosphines bound on solid support, imply that the regenerated agents can be used repeatedly, resulting in minimized costs and optimized processes, especially for applications on a more industrial scale. The solid support

As noted above, either the tertiary phosphine oxide or the reducing phosphine can be attached to a solid support. An example of such a solid support is a polystyrene material, as sold under the trade name JandaJel ™, by Sigma-Aldrich Co. Other possible solid phase supports are, for example, silica gel, Olefin Polymerization Gel by Metathesis Opening Ring (ROMP) etc.

The person of ordinary skill in the art will know of several other possible solid supports, such as those described, for example, in U.S. Patent Number 7,491,779 to Steinke, et al., The content of which is incorporated herein by reference.

Bonding to the solid support is accomplished through the use of well-known chemistry to bind compounds of the present type to a solid phase, and the skilled person is well trained to select the appropriate reaction conditions and reagents. For example, polystyrene-bound triphenylphosphine can be prepared by copolymerization of diphenyl-styrene-phosphine and styrene or by copolymerization of diphenyl-phosphine and poly (4-bromo-styrene). Other features of the invention process

As can be seen from the Examples that will follow, which are intended for illustrative purposes only, and which are not to be understood as limiting the scope of the invention, the process of the invention can very advantageously be carried out at low reaction temperature, for example, temperature environment (for example, 18-25 ° C), and is preferably carried out under an inert atmosphere, for example, a nitrogen atmosphere. Very advantageously, the reaction time can be kept very short, ie less than 1 hour, for example, from 10 minutes to 30 minutes, giving a very high product yield of, for example, above 90% by mol, and up to 99 mol% or even an almost quantitative yield.

In one embodiment of the process of the invention, tertiary phosphine oxide, reducing tertiary phosphine and a catalyst are mixed, optionally in an anhydrous aprotic solvent. The mixture is stirred for the appropriate amount of time under an inert atmosphere. The reaction mixture is then suitably inactivated, for example, by the addition of water.

The product can be extracted, purified and crystallized, for example, following the procedure described in the Examples. For example, in one embodiment, on completion of the reaction, the reaction medium is diluted, if necessary, and washed with portions of a weak basic buffer solution, such as saturated NaHCO3. The solution is dried, for example, with Na2SO4 and filtered, then the solvent is evaporated. The evaporation residue is redissolved in a hot solvent, for example, EtOH, and forced to crystallize, for example, when left in a refrigerator. The product crystals are then filtered, washed and dried. Of course, many variants of this procedure and modifications of it will present themselves to the person with common experience in the art, and all are considered to fall within the scope of the invention. Examples EXAMPLE 1 100 mg (0.153 mmol) of 2,2'-Bis (diphenyl-oxy-phosphine) -1, l'-binaftyl were treated with 4 mg (16 μmols) of I2 and 150 μL (0.6 mmol) of tributylphosphine in 1 ml of acetonitrile / THF (1: 1 v / v). The mixture was stirred at room temperature for 10 minutes under a nitrogen atmosphere before being inactivated with H2O (100 μL). The reaction mixture was diluted with ethyl acetate (10 ml) and was washed with portions of sat. (3x5 mL). The organic fraction was dried over filtered Na2SO4 and the solvent was evaporated in vacuo. The resulting residue was recrystallized from EtOH, the resulting crystals were filtered, washed and dried in vacuo, giving 88 mg (0.141 mmol, 92%) of 2,2'-Bis (diphenyl-phosphine) -1, l'-binaftyl ( BINAP). EXAMPLE 2 100 mg (0.186 mmol) of Bis (2- (diphenyl-oxy-phosphine) -phenyl-ether were treated with 5 mg (20 μmol) of I2 and 185 μL (0.74 mmol) of tributyl-phosphine in 1 mL of acetonitrile / THF (1: 1 v / v). The mixture was stirred at room temperature for 10 minutes under a nitrogen atmosphere before being inactivated with H2O (100 μL). The reaction mixture was diluted with ethyl acetate (10 ml) and was washed with portions of sat. NaHCO3 (3x5 ml). The organic fraction was dried with Na2SO4, filtered and the solvent was evaporated in vacuo. The resulting residue was recrystallized from 1-propanol, the resulting crystals were filtered, washed and dried in vacuo, giving 94 mg (0.175 mmol, 94%) of Bis (2- (diphenyl-phosphine) -phenyl-ether (DPEfos)). EXAMPLE 3 100 mg (0.164 mmol) of 9,9-Dimethyl-4 , 6-bis (diphenyl-oxy-phosphine) -xanthene were treated with 4 mg (16 μmol) of I2 and 162 μL (0.65 mmol) of tributyl-phosphine in 1 ml of acetonitrile / THF (1: 1 v / v) The mixture was stirred at room temperature for 10 minutes under a nitrogen before being inactivated with H2O (100 μL). The reaction mixture was diluted with ethyl acetate (10 ml) and was washed with portions of sat. (3x5 mL). The organic fraction was dried over Na2SO4, filtered and the solvent was evaporated in vacuo. The resulting residue was recrystallized from 1-propanol, the resulting crystals were filtered, washed and dried in vacuo, giving 90 mg (0.156 mmol, 95%) of 9,9-dimethyl-4,6-bis (diphenyl-oxy-phosphine) ) - xanthene (Xanthfos). EXAMPLE 4 100 mg (0.171 mmol) of l'-Bis (diphenyl-oxy-phosphine) - ferrocene were treated with 4 mg (16 μmol) of I2 and 170 μL (0.68 mmol) of tributyl-phosphine in 1 ml of acetonitrile / THF (1: 1 v / v). The mixture was stirred at room temperature for 10 minutes under a nitrogen atmosphere before being inactivated with H2O (100 μL). The reaction mixture was diluted with ethyl acetate (10 ml) and was washed with portions of sat. (3x5 mL). The organic fraction was dried over Na2SO4, filtered and the solvent was evaporated in vacuo. The resulting residue was recrystallized from ethanol, the resulting crystals were filtered, washed and dried in vacuo, giving 89 mg (0.160 mmol, 94%) of 1,1'-Bis (diphenyl-phosphine) -ferrocene (dppf). EXAMPLE 5 100 mg (0.262 mmol) of tris (4-chloro-phenyl) -phosphine oxide were treated with 6 mg (26 μmol) of I2 and 130 μL (0.52 mmol) of tributyl-phosphine in 1 ml of acetonitrile / THF (1: 1 v / v). The mixture was stirred at room temperature for 10 minutes under a nitrogen atmosphere before being inactivated with H2O (100 μL). The reaction mixture was diluted with ethyl acetate (10 ml) and was washed with portions of sat. (3x5 mL). The organic fraction was dried over Na2SÜ4, filtered and the solvent was evaporated in vacuo. The resulting residue was recrystallized from methanol (2 ml). The resulting crystals were filtered, washed and dried in vacuo, giving 95 mg (0.260 mmol, 99%) of tris (4-chloro-phenyl) -phosphine. EXAMPLE 6 100 mg (0.359 mmol) of triphenyl phosphine oxide were treated with 9 mg I2 (35 μmol) and tributyl phosphine 180 μL (0.72 mmol) in 1 ml of acetonitrile / THF (1: 1 v / v ). The mixture was stirred at room temperature for 10 minutes under a nitrogen atmosphere before being inactivated with H2O (100 μL). The reaction mixture was diluted with ethyl acetate (10 ml) and was washed with portions of sat. (3x5 mL). The organic fraction was dried with Na2SC> 4, filtered and the solvent was evaporated in vacuo. The resulting residue was recrystallized from methanol, the resulting crystals were filtered, washed and dried in vacuo, giving 88 mg (0.334 mmol, 93%) of triphenylphosphine. EXAMPLE 7 3 g (0.12-0.18 mmol) of polymer-bound triphenylphosphine oxide on polystyrene support (31P NMR, bs, 24.5 ppm), were treated with 12,270 mg (1.07 mmols) and 2 ml (8 mmol) of tributyl phosphine in 12 ml of acetonitrile / THF (1: 1 v / v). The mixture was stirred at room temperature for 4 hours under a nitrogen atmosphere after which the solid support was filtered and washed with THF (10 ml). The solid support was analyzed by P NMR, no sign of triphenyl phosphine oxide could be seen, only polymer-bound triphenyl phosphine in the polystyrene support (31P NMR, bs, - 6.9 ppm). EXAMPLE 8 100 mg (0.359 mmol) of triphenyl phosphine oxide were treated with 9 mg (35 μmol) of I2 and 180 μL (0.72 mmol) of tributyl phosphine in 1 ml of acetonitrile / toluene (1: 1 v / v) using the general procedure according to Example 6. Essentially the same results were obtained as in Example 6. EXAMPLE 9 100 mg (0.359 mmol) of triphenylphosphine oxide were treated with 9 mg (35 μmol) of I2 and 180 μL (0.72 mmol) of tributylphosphine in 1 mL of acetonitrile / diethyl ether (1: 1 v / v) using the general procedure according to Example 6. Essentially the same results were obtained as in Example 6. EXAMPLE 10 100 mg (0.359 mmol) of triphenylphosphine oxide were treated with 9 mg (35 μmol) of I2 and 180 μL (0.72 mmol) of tributylphosphine in 1 ml of acetonitrile / EtOAc (1: 1 v / v) using the general procedure according to Example 6. Essentially the same results were obtained as in Example 6. EXAMPLE 11 100 mg (0.359 mmol) of triphenylphosphine oxide were treated with 9 mg (35 μmol) of I2 and 106 μL (0.72 mmol) of triethyl phosphine in 1 ml of acetonitrile using the general procedure according to Example 6. Essentially the same results were obtained as in Example 6. EXAMPLE 12 100 mg (0.431 mmol) of tri (2-furyl) -phosphine oxide (31P NMR, s, -15.4) were treated with 11 mg (43 μmol) of I2 and 180 μL (0.70 mmol) of tributyl- phosphine in 2 ml of acetonitrile / THF (1: 1 v / v) for 19 hours at room temperature, which gave conversion of tri (2-phyryl) -phosphine integrated by 31P NMR (31P NMR, s, -76.5) in ca. 50%. EXAMPLE 13 100 mg (0.359 mmol) of triphenylphosphine oxide were treated with 9 mg (35 μmol) of I2 and 202 mg (0.72 mmol) of tricyclohexylphosphine in 1 ml of acetonitrile using the general procedure of according to Example 6. Essentially the same results were obtained as in Example 6. EXAMPLE 14 100 mg (0.359 mmol) of triphenylphosphine oxide were treated with 2 μL (35 μmol) of Br2 and 180 μL (0.72 mmol) ) of tributylphosphine in 1 ml of acetonitrile using the general procedure according to Example 6. Essentially the same results were obtained as in Example 6. EXAMPLE 15 100 mg (0.359 mmol) of triphenylphosphine oxide were treated with 12 mg (35 μmol) of triphenylphosphine dichloride and 180 μL (0.72 mmol) of tributylphosphine in 1 ml of acetonitrile for 48 hours at room temperature. Essentially the same results were obtained as in Example 6. EXAMPLE 16 100 mg (0.359 mmol) of triphenylphosphine oxide were treated with 3 μL (35 μmol) of CC14 and 180 μL (0.72 mmol) of tributyl-phosphine in 1 ml acetonitrile using the general procedure according to Example 6. Essentially the same results as those of Example 6 were obtained.

Claims (12)

1. Process for the conversion of a tertiary phosphine oxide to the corresponding tertiary phosphine, characterized by the fact that it comprises reacting this tertiary phosphine oxide with a reducing tertiary phosphine, in the presence of a halogen-containing compound selected from the group comprising chlorine, bromine, iodine, cyanuric chloride, halo-alkanes and phosphine dihalides as a catalyst that catalyzes the conversion. 2. Process according to claim 1, characterized by the fact that a tertiary phosphine oxide of formula (I)

wherein each R1, R2 and R3 is independently selected from the group comprising straight or branched, substituted or unsubstituted hydrocarbyl; and substituted or unsubstituted carbocyclyl or heterocyclyl; A is a linking group; m is an integer from 0 to 2; is converted to the corresponding tertiary phosphine of formula (III)

in which R1, R2, R3, A and m are as defined herein above; by reaction with a reducing tertiary phosphine of formula (II)

wherein each R4, R5 and R6 is independently selected from the group comprising straight or branched, substituted or unsubstituted hydrocarbyl; and substituted or unsubstituted, aliphatic or aromatic carbocyclyl or heterocyclyl; B is a linking group; and n is an integer from 0 to 2; in the presence of a catalyst for the reaction. Process according to claim 2, characterized in that each A and B is independently selected from substituted or unsubstituted hydrocarbilene, monocyclic or polycyclic carbocyclylene, substituted or unsubstituted, monocyclic or polycyclic heterocyclylene, substituted or unsubstituted and metallocenylene substituted or unsubstituted. Process according to any one of claims 1 to 3, characterized in that the catalyst is selected from the group comprising chlorine, bromine, iodine, cyanuric chloride, tetrahalo-methanes, and phosphine dihalides. Process according to any one of claims 1 to 4, characterized in that the process is carried out under solvent-free conditions or in an anhydrous aprotic solvent. Process according to claim 5, characterized in that the anhydrous aprotic solvent is selected from the group comprising tetrahydro-furan, acetonitrile, diethyl ether, propionitrile, toluene, ethyl acetate and mixtures thereof. Process according to any one of claims 1 to 6, characterized in that the reducing tertiary phosphine is added to the reaction mixture in a molar ratio of the reducing phosphine function (s) of the reducing tertiary phosphine to the phosphine oxide function (s) of tertiary phosphine oxide of at least 1. Process according to any one of claims 1 to 7, characterized in that the basicity of the reducing tertiary phosphine is greater than the basicity of the tertiary phosphine of the product. Process according to any one of claims 15 to 8, characterized in that the tertiary phosphine oxide to be reduced is attached to a solid support. Process according to any one of claims 1 to 9, characterized in that the reducing tertiary phosphine is attached to a solid support. 11. Use of a tertiary phosphine, characterized by the fact that it is to reduce a tertiary phosphine oxide by the reaction of said tertiary phosphine oxide with tertiary phosphine in the presence of a compound containing halogen selected from the group comprising chlorine, bromine, iodine, chloride cyanuric, halo-alkanes and phosphine dihalides as a catalyst. 12. Use according to claim 11, characterized by the fact that the tertiary phosphine is attached to a solid support.