FR2800371A1 - Sulfonylamides and carboxamides ligands and their transition metal complexes useful for the asymmetric syntheses of chiral secondary alcohols from ketones - Google Patents

Abstract

Sulfonylamide and carboxamide derivatives (I) are new. Sulfonylamide and carboxamide derivatives of formula (I) are new. B' = -CO-, or -SO2-; Rf = halo, alkyl or cycloalkyl that is mono-, poly- or per-halogenated and may be interrupted by one or more O or S, aryl substituted by halogenated alkyl, mono-, poly- or perhaloaryl, RaCF2-, RaCF2-CF2-, RaCF2CF(CF3)-, CF2-C(Ra)F-, or (CF3)Ra-; Ra = H or Rb; Y' = OH, SH, NH2, NHRb, or NRbRc; Rb, Rc = alkyl or alkenyl (optionally interrupted by one or more O, S, or CO and optionally substituted by one or more halo or carboxyl), aryl (optionally substituted by one or more halo, alkyl or alkenyl), aralkyl or aralkenyl (both optionally substituted by halo); A = a group of formulae (i) or (ii); R', R'' = 1-20C hydrocarbon which may be acyclic, cycloaliphatic (saturated, unsaturated, aromatic mono or polycyclic), and may incorporate one or more hetero atoms and may be substituted by aliphatic groups in which the alkyl chain may be interrupted by O, CO, and may be substituted by an aromatic or non-aromatic ring, and these groups may further be halogenated (with the proviso that when B is SO2n is zero, Rf is CF3, and Y is NH2, then R' and R'' are not both unsubstituted phenyl), or R' and R'' together may form a cycloaliphatic group as defined above; X = methylene optionally substituted; n = 0-3; Ar1, Ar2 = aromatic rings (optionally substituted and optionally condensed, and optionally ortho-ortho or ortho-peri condensed between themselves; x and y = two double bonds between the skeleton A and the groups amino and Y. Independent claims are also included for: (1) the preparation of (I); (2) transition metal complexes of formula (IV); (3) the preparation of secondary alcohols of formula RbCH(OH)Rc by asymmetric reduction of ketones of formula RbC(O)Rc using the transition metal complexes (IV). M = Rh, Ru, Re, Ir, Co, Ni, Pt, or Pd; Z = an anionic ligand ; L = an unsaturated aliphatic ligand having at least one double bond or a carbocyclic or heterocyclic ligand having at least one double bond, that may be charged. The bonds x and y being in the same absolute configuration.

Description

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 The main subject of the present invention is new compounds of the diamine, mono- or polyfluorinated, sulphonylated or carbonyl type, their method of preparation and their application in asymmetric catalysis.

 These novel compounds are particularly useful in their optically active form as ligands of organometallic complexes. The corresponding metal complexes are particularly advantageous as catalysts for carrying out the asymmetric synthesis.

 By way of illustration of these reactions of asymmetric organic syntheses, mention may be made especially of asymmetric catalytic hydrogenation and more particularly of ketone derivatives in their corresponding chiral secondary alcohols.

 The optically active secondary alcohol derivatives are reagents particularly sought after in many fields, in particular pharmaceutical, agrochemical or perfume.

 Of course, during the synthesis of this type of product, there is generally a simultaneous production of an inactive enantiomer which it is necessary to isolate the desired enantiomer.

 It is therefore important to minimize the formation of this enantiomer without interest. For this purpose, the ketone derivative reductions are conventionally conducted in the presence of asymmetric synthesis catalysts. Generally, these are transition metal complexes carrying chiral ligands. Thus, certain organometallic complexes of the Rh (I), lr (I) and Ru (II) chirally modified types make it possible to drive the reduction of aromatic ketones with a very high substrate / catalyst ratio.

 However, the enantioselectivity obtained with this type of catalyst remains moderate.

 More recently, a new type of chiral catalysts based on Ru (ll) has been developed which allows a reduction of

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enantioselective aromatic ketones at room temperature. (R Noyori et al., J. Am Chem Soc., 1995, 117, 7562, 7563)
This catalyst is derived from the metal complex RuCl 2 (# 6 mesitylene) 2.

dans laquelle Ra représente un radical choisi parmi C6H5CO-, pCH3OC6H4SO2-, C6H5SO2- et CF3S02 . En fait, parmi les radicaux sulfonés testés, c'est le radical CF3SO2- qui est considéré comme le ligand le moins intéressant en terme de rendement énantiosélectif. This is used in a chelated form with a diphenylethylenediamine derivative of formula A

wherein Ra represents a radical selected from C6H5CO-, pCH3OC6H4SO2-, C6H5SO2- and CF3SO2. In fact, among the sulphonated radicals tested, it is the radical CF3SO2- which is considered to be the least interesting ligand in terms of enantioselective yield.

 The object of the present invention is precisely to propose novel diamino derivatives or analogues capable of constituting chiral ligands effective for asymmetric synthesis and in particular for the asymmetric hydrogenation of ketonic functions.

dans laquelle - B représente (i) -CO-, ou (ii)-SO2-, It has now been found and this constitutes a first object of the invention of new products, namely diamino derivatives or analogues having the following general formula:

in which - B represents (i) -CO-, or (ii) -SO2-,

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 Rf represents (i) a halogen atom, preferably fluorine, (ii) an alkyl radical preferably of C1 to C12 or cycloalkyl preferably of C3 to C12, mono-, poly- or perhalogenated whose chain haloalkyl is optionally interrupted by one or more oxygen or sulfur atom (s), (iii) an aryl radical, preferably a C6-C12 'radical substituted with at least one halogenated alkyl radical as defined in (ii), ( iv) an aryl radical, mono-, poly- or perhalogenous preferably C6 to C12, or (v) a radical selected from RA-CF2-, RA-CF2-CF2-, RA-CF2-CF (CF3) -, CF3-C (RA) F- and (CF3) RA- with RA representing a hydrogen atom or having any of the meanings given below for RB and Rc, - Y represents an OH, SH group, NH 2, NHRB or NRBRC, with RB and Rc being different from a hydrogen atom and representing, independently of one another, a radical chosen from: (i) an alkyl chain, preferably a C 1 to C 10 alkyl chain, optionally It is interrupted by one or more oxygen or sulfur atom (s) or carbonyl function (s) and optionally substituted with one or more halogen atoms or carboxyl groups, (ii) an alkenyl chain, preferably a C 2 -C 10 alkenyl chain. optionally interrupted by one or more atom (s) or sulfur or carbonyl function (s) and optionally substituted with one or more halogen atom (s) or carboxyl group (s); (iii) an aryl group, preferably C6 to C12, optionally substituted with one or more halogen atoms or alkyl or alkenyl group (s); (iv) an arylalkyl group, preferably C7 to C15, optionally substituted with one or more halogen atom (s); (v) an arylalkenyl group, preferably C8 to C15, optionally substituted by one or more halogen atom (s);

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dans lesquelles - R' et R" représentent indépendamment l'un de l'autre un radical hydrocarboné ayant de 1 à 20 atomes de carbone qui peut être un radical aliphatique acyclique saturé ou insaturé, linéaire ou ramifié ; un radical cycloaliphatique saturé, insaturé, aromatique, monocyclique ou polycyclique incorporant ou non un ou plusieurs hétéroatomes sous réserve que lorsque B représente un groupement SO2, n a pour valeur zéro, Rf représente un groupement CF3, Y représente un groupement NH2 alors R' et R" ne représentent pas simultanément un noyau phényle non substitué ; ledit radical cycloaliphatique étant le cas échéant porteur d'un radical aliphatique saturé ou insaturé, linéaire ou ramifié avec la chaîne alkyle pouvant être interrompue par un ou plusieurs atomes d'oxygène et/ou fonction carbonyle et le cas échéant substituée de préférence en fin de chaîne par un radical cyclique aromatique ou non ;lesdits radicaux pouvant le cas échéant être substitués par un ou plusieurs atomes d'halogène, de préférence le fluor et/ou un ou plusieurs radicaux alkyles en C1 à Ce de préférence en C1 à C4 ou encore les deux substituants R' et R" sont liés entre eux de manière à constituer un radical cycloaliphatique tel que défini ci-dessus, - X représente un groupement méthylène le cas échéant substitué, - n est un entier variant de zéro à 3, et - symbolized a skeleton of general formula la or Ib.

in which - R 'and R "represent, independently of one another, a hydrocarbon radical having from 1 to 20 carbon atoms which may be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated cycloaliphatic radical; aromatic, monocyclic or polycyclic, with or without one or more heteroatoms, provided that when B represents a group SO2, na is zero, Rf represents a group CF3, Y represents a group NH2, then R 'and R "do not simultaneously represent a ring unsubstituted phenyl; said cycloaliphatic radical being optionally carrying a saturated or unsaturated aliphatic radical, linear or branched with the alkyl chain which may be interrupted by one or more oxygen atoms and / or carbonyl function and, if appropriate, preferably substituted at the end of chain by an aromatic cyclic radical or not, said radicals may optionally be substituted by one or more halogen atoms, preferably fluorine and / or one or more alkyl radicals C1 to C6 preferably C1 to C4 or the two substituents R 'and R "are linked to one another so as to constitute a cycloaliphatic radical as defined above, X represents a methylene group which may be substituted, n is an integer ranging from zero to 3, and

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 Ar 1 and Ar 2 represent, independently of one another, two substituted or unsubstituted aromatic rings, condensed or not, and optionally carrying one or more heteroatoms, preferably C 8 to C 12, which may form ortho or ortho systems and peri-condensed between them, x and y respectively locate the two bonds established between the skeleton symbolized by A and the amino groups and Y and its derivatives.

 For the purposes of the present invention, the term "derivatives" is intended to cover, in particular, the organic or inorganic salts of the compounds of formula 1 as well as their racemic mixtures and their optically active isomers.

 Unexpectedly, and in contradiction with the results published with the trifluoromethanesulfonyl derivative of formula A, mentioned above, the inventors have demonstrated that the presence of a strongly electron-withdrawing group at the level of one or of the amine functions allowed to significantly improve the asymmetric reductions of ketones when catalysed by the corresponding metal complexes.

 The kinetics of the reaction are significantly increased and the expected enantiomer is recovered with a higher conversion rate for equivalent enantiomeric yield.

 Thus, the electron-withdrawing group is particularly effective when it comprises in its structure at least one halogen atom and more preferably a fluorine atom.

 According to the invention, the electron-withdrawing group appearing on the nitrogen atom of the amine function of the general formula I is represented by a group BRf in which Rf represents (i) a halogen atom, preferably fluorine, (ii) a C 1 to C 10 alkyl radical or C 3 to C 10 cycloalkyl mono-, poly- or perhalogenated, (iii) a phenyl radical substituted with at least one mono-, poly- or poly (C 1 -C 4) alkyl radical; - halogenated, or

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 (iv) a mono-, poly- or perhalogenated C 6 aryl radical.

 More preferably, Rf represents a radical CF3, C4F9 or a phenyl radical substituted with one or more halogen atoms, preferably fluorine, or with one or more mono-, poly- or perfluorinated C1-C2 alkyl groups.

 The compounds in which B is SO 2 are particularly interesting.

 As a preferred example of Y groups, there may be mentioned more particularly the NH 2 and NHRB radicals, with RB as defined above.

 In the preceding general formulas and which follow, the halogen atom or atoms mentioned as substituent are preferably represented by a fluorine atom.

dans laquelle : Rf, (x), (y) et Y sont tels que définis précédemment et Ar1 et Ar2 figurent ensemble un groupement aromatique. According to a first variant of the invention, the compounds of general formula # correspond to the general formula b

wherein: Rf, (x), (y) and Y are as previously defined and Ar1 and Ar2 together represent an aromatic moiety.

 In the following description of the present invention, aromatic is understood to mean the classical notion of aromaticity as defined in the literature, in particular by J. March Advanced Organic Chemistry, 4th ed., John Wiley & Sons, 1992, pp 40 and following. In the context of the present invention, the aromatic derivative may be monocyclic or polycyclic.

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 In the case of a monocyclic derivative, it may comprise at its ring level one or more heteroatoms chosen from nitrogen, phosphorus, sulfur and oxygen atoms. According to a preferred mode, they are nitrogen atoms.

 By way of illustration of the monocyclic heteroaromatic derivatives which are suitable for the present invention, there may be mentioned the pyridine, pyrimidine, pyridosine and pyrasinic derivatives.

 The carbon atoms of the aromatic derivative can also be substituted. Two vicinal substituents present on the aromatic ring may also form together with the carbon atoms which carry them a hydrocarbon ring, preferably aromatic, and optionally comprising at least one heteroatom. The aromatic derivative is then a polycyclic derivative.

 As an illustration of this type of compounds, there may be mentioned derivatives of naphthalene, quinoline and isoquinoline.

 As a representative of the compounds corresponding to the general formula b, there may be mentioned more particularly those in which Ar 1 and Ar 2 are together either a group derived from diphenyl-2,2'-diyl or a dinaphthyl group-2,2. '-diyle.

 In the case where Ar 1 and Ar 2 together represent a diphenyl-2,2'-yl group, the two phenyl rings are substituted so as to block the configuration of the corresponding structure.

 The compounds of general formula 1 in which A symbolizes a skeleton of formula la prove in fact particularly interesting.

générale l'a Ru ( x N S 02 Rf ('a) Y -S02Rf (1' a) ( )n R" (y) More preferably, these compounds correspond to the formula

general a Ru (x NS 02 Rf ('a) Y -S02Rf (1' a) () n R "(y)

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 in which - Rf, X, n, (x), (y) and Y are as defined above in general formula 1, and - R 'and R "represent, independently of one another, a carbocyclic radical or heterocyclic, saturated, unsaturated, aromatic, monocyclic or polycyclic, provided that when n is zero, Rf is CF3, Y is NH2, then R 'and R "do not simultaneously represent an unsubstituted phenyl ring or R' and R "may be bonded so as to constitute with the carbon atoms which carry them a carbocyclic or heterocyclic radical having from 4 to 20 saturated, unsaturated, aromatic, monocyclic or polycyclic atoms.

 In the general formulas 1a and 1a, R 'and R ", which may be identical or different, may have various meanings, various examples are presented below but they are in no way limiting.

 Thus, R 'and R "may independently of each other represent an acyclic aliphatic radical, saturated or unsaturated, linear or branched.

 More precisely, R 'and R "represent an aliphatic, acyclic, linear or branched radical preferably having 1 to 12 carbon atoms, saturated or comprising one to several, generally 1 to 3, double bonds. optionally interrupted by a group, preferably a heteroatom, and more particularly, an oxygen or nitrogen atom or a carrier of substituents, for example a halogen atom, in particular chlorine or a -CF3 group. This linear or branched, saturated or unsaturated, acyclic aliphatic radical can optionally carry a cyclic substituent, The term "ring" is understood to mean a saturated, unsaturated or aromatic carbocyclic or heterocyclic ring, and substituents may be used as examples of cyclic substituents. cycloaliphatic, aromatic or heterocyclic, in particular cycloaliphatic compounds comprising 6 carbon atoms in the ring or benzenes, these

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 cyclic substituents being optionally themselves carrying one or more substituents.

 As examples of such radicals, mention may in particular be made of the benzyl radical.

 In the general formulas 1 and a, the radicals R 'and R "may also represent, independently of one another, a saturated carbocyclic radical or comprising 1 or 2 unsaturations in the ring, generally having from 3 to 8 carbon atoms. carbon, preferably 6 carbon atoms in the ring, said ring being substitutable.

As preferred examples of this type of radical, mention may be made of cyclohexyl radicals optionally substituted by linear or branched alkyl radicals having from 1 to 4 carbon atoms.

 R 'and R "may also be linked to represent carbocyclic or heterocyclic radicals, mono- or poly-cyclic, saturated, unsaturated or aromatic, preferably bicyclic which means that at least two rings have two carbon atoms in common. In the case of polycyclic compounds, the number of carbon atoms in each ring preferably ranges from 3 to 6, the total number of carbon atoms being preferably 5.

As an illustration of this type of structure, mention may be made in particular of the following cyclic radicals:

Thus, the radicals R 'and R "may independently of one another represent, in a preferred embodiment, an aromatic hydrocarbon radical, and in particular a benzene radical corresponding to the general formula

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dans laquelle : - n' représente un entier de 0 à 5 et - Q un radical choisi parmi : # un radical alkyle linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, # un radical alkoxy linéaire ou ramifié, ayant de 1 à 4 atomes de carbone, # un groupe benzoyle, # un groupe-OH, # un groupe -NH2, # un groupe -NO2, # un radical phényle, # un atome d'halogène, # un groupe CF3, # un groupe SRD, ou # un groupe ORD avec RD répondant à la définition figurant ci- dessus pour RB.

in which: n 'represents an integer of 0 to 5 and - Q a radical chosen from: # a linear or branched alkyl radical having from 1 to 4 carbon atoms, # a linear or branched alkoxy radical having from 1 to 4 carbon atoms, # a benzoyl group, # an OH group, # a -NH 2 group, # a -NO 2 group, # a phenyl group, # a halogen atom, # a CF 3 group, # a SRD group, or # an ORD group with RD as defined above for RB.

 R 'and R "may also independently of one another represent a polycyclic aromatic hydrocarbon radical with rings which may form between them ortho-condensed, ortho- and peri-condensed systems, more particularly a naphthyl radical; can be substituted.

 R 'and R "may also independently of one another represent a saturated, unsaturated or aromatic heterocyclic radical, in particular having 5 or 6 atoms in the ring, one or two of which

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 heteroatoms such as nitrogen, sulfur and oxygen atoms; the carbon atoms of this heterocycle may also be substituted.

 R 'and R "may also represent a polycyclic heterocyclic radical defined as being either a radical consisting of at least two aromatic or non-aromatic heterocycles containing at least one heteroatom in each ring and forming ortho or ortho- and peri-condensed orthogonal systems between them, or either a radical condensed by at least one aromatic or non-aromatic hydrocarbon ring and at least one aromatic or non-aromatic heterocycle forming between them ortho- or ortho- and peri-condensed systems, the carbon atoms of said rings possibly being substituted.

 As examples of R 'and R "groups of heterocyclic type, mention may be made, inter alia, of furyl, pyrrolyl, thienyl, isoxazolyl, furazanyl, isothiazolyl, imidazolyl, pyrazolyl, pyridyl, piridazinyl, pyrimidinyl and pyranyl radicals. quinolyl, naphthyridinyl, benzopyranyl, benzofuranyl, indolyl.

 The number of substituents present on each ring depends on the carbon condensation of the ring and the presence or absence of unsaturation on the ring. The maximum number of substituents which can be carried on a ring is readily determined by those skilled in the art.

 By way of examples of the compounds of general formula a, there may be mentioned more particularly those in which n has the value 0.

 Of particular interest are the compounds of general formula Ia wherein: - R 'and R "both represent a phenyl group, provided that when Rf is CF3 and Y is NH2 then at least one of R 'and R "are at least monosubstituted or - R' and R" are bonded together so as to form with the carbon atoms which carry them a cyclohexyl radical.

 As a representative of this type of compounds, there may be mentioned ammonium chloride of (1S, 2S) -N-trifluoromethanesulfonyl-1,2-

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 cyclohexanediamine, (1S, 2S) -N-trifluoromethanesulfonyl-1,2cyclohexanediamine, (1S, 2S) -N-trifluoromethanesulfonyl-1,2cyclohexanediamine, (1S, 2S) -NN- (Nonafluorobutanesulfonyl) -1, 2-diphenylethylenediamine, (1S, 2S) -N- (Nonafluorobutanesulfonyl) -1,2-cyclohexanediamine, (1S, 2S) -N- (pentafluorophenylsulfonyl) -1,2-cyclohexanediamine, (1S, 2S) - N- (Pentafluorophenylsulfonyl) -1,2-diphenylethylenediamine, (1S, 2S) -N- (3,5-bis (trifluoromethane) phenylsulfonyl) 1,2-cyclohexanediamine, (1S, 2S) -N- (3 5-bis (trifluoromethane) phenylsulfonyl) 1,2-diphenylethylenediamine.

 As mentioned above, the compounds of general formula # are particularly advantageous when they are in optically active form.

 For this purpose, the two carbons of the general formula 1 involved respectively at the level of the bonds symbolized by (x) and (y) constitute two centers of chirality which are preferably of the same configuration.

 Another object of the invention resides in the process for preparing the compounds of general formula I.

avec A et Y étant tels que définis ci-dessus avec un composé de formule généraient
Rf-B-X' (III) More specifically, the subject of the present invention is a process for preparing a compound of general formula # in which a compound of general formula II is reacted.

with A and Y being as defined above with a compound of general formula
Rf-BX '(III)

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 with Rf and B being as defined above and X 'representing a halogen atom, preferably chlorine or fluorine, or in the case where B represents SO2 a group OS02Rf and in that said compound is recovered; of general formula I.

 In fact, the operating conditions used to carry out the synthesis of the compounds of general formula 1 according to the process claimed are generally dictated by the chemical nature of the starting compounds. The implementation of this type of reaction is in fact within the skill of those skilled in the art.

 The reaction may be carried out in a usual organic solvent and preferably in dichloromethane or 1,2-dichloroethane.

 The temperature is generally between 0 ° C. and the reflux of the solvent and is preferably close to or equal to the ambient temperature.

 Generally the reaction is conducted at atmospheric pressure.

It is also preferred to conduct the reaction under an atmosphere composed of inert gases such as nitrogen or rare gases, for example argon. From a practical point of view, the process can be carried out batchwise or continuously.

 A practical embodiment is to charge the derivative of formula II in the solvent and then slowly add the sulfonylating agent of formula III.

 The reaction is carried out for a period of time sufficient to obtain the conversion of the product of formula II into formula I. The final compound is isolated by standard reaction medium techniques.

 It is possible to carry out the reaction discussed above in the presence of a base. The amount of this base is adjusted so as to trap the released halogenated acid. Generally, it is in excess of up to 3 times the stoichiometric amount.

 As mentioned above, the compounds of general formula I, a and b are particularly interesting in their optically active form.

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 Thus, the present invention also relates to the use of a compound of general formulas I, a and b, in an optically active form for the preparation of catalytic metal complex ligands useful for carrying out asymmetric syntheses. in organic chemistry.

 The compounds of formulas I, a and b, in optically active form thus prove to be particularly useful for the preparation of catalytic metal complex ligands useful for carrying out an enantioselective asymmetric hydrogenation of ketone derivatives.

 It has also been shown that these same compounds of general formulas I, a and b, in optically active form could be used to prepare catalytic metal complex ligands useful for enantioselective oxidation of hydroxyl functions.

 Accordingly, the present invention also relates to a metal complex based on a transition metal and comprising as ligand of said metal at least one optically active form of a compound of general formulas I, a and l ' b, as defined above.

 As examples of transition metals capable of forming complexes in accordance with the present invention, mention may in particular be made of metals such as rhodium, ruthenium, rhenium, iridium, cobalt, nickel, platinum and palladium.

 Of the above metals, rhodium, ruthenium and iridium are preferred.

 As examples of metal complexes according to the present invention, mention may be made more particularly of those corresponding to the general formula IV

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dans laquelle : - A, B, Rf et Y sont tels que définis précédemment en formule I, - les carbones portant les liaisons (x) et (y) possèdent la même configuration absolue, - M est un métal de transition choisi parmi le rhodium, le ruthénium, le rhénium, l'iridium, le cobalt, le nickel, le platine et le paladium, - Z représente un ligand anionique coordinant et - L représente un ligand aliphatique insaturé comprenant au moins une double liaison ou un ligand carbocyclique ou hétérocyclique de préférence de 5 à 8 atomes et comprenant au moins une double liaison, chargé ou non.

in which: - A, B, Rf and Y are as defined above in formula I, - the carbons bearing the bonds (x) and (y) have the same absolute configuration, - M is a transition metal chosen from rhodium , ruthenium, rhenium, iridium, cobalt, nickel, platinum and palladium, - Z represents a coordinating anionic ligand and - L represents an unsaturated aliphatic ligand comprising at least one double bond or a carbocyclic or heterocyclic ligand preferably from 5 to 8 atoms and comprising at least one double bond, charged or not.

 As the valency at the metal atom is likely to vary, the nature and number of ligands L and Z are then adjusted accordingly by those skilled in the art.

 Of particular interest are the compounds of formula IV in which - M represents ruthenium, rhodium or iridium, - Z represents a halogen atom, preferably chlorine or bromine, - L represents a C6 to C12 aromatic ligand or a cyclopentadienyl or cyclooctatriene ligand optionally substituted by one or more C1-C4 alkyl groups.

 Preferably, this complex corresponds to the general formula IVa

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dans laquelle : - R' et R" représentent indépendamment l'un de l'autre un radical carbocyclique ou hétérocyclique en C1 à C20 saturé, insaturé, aromatique, monocyclique ou polycyclique tel que défini précédemment, sous réserve que lorsque Rf représente un groupement CF3, Y un groupement NH2 alors R' et R" ne représentent pas simultanément un noyau phényle non substitué ou R' et R" sont liés entre eux de manière à constituer avec les atomes de carbone qui les portent un radical carbocyclique ou hétérocyclique de 4 à 20 atomes saturé, insaturé, aromatique, monocyclique ou polycyclique, et - Rf représente (i) un atome d'halogène, de préférence le fluor, (ii) un radical alkyle en C, à C10 ou cycloalkyle en C3 à C10, polyou per-halogéné, (iii) un radical phényle substitué par au moins un radical en C1 à C4 polyhalogéné, (iv) un radical phényle mono-, poly- ou per- halogéné et - Y, L et Z sont tels que définis ci-dessus.

in which: R 'and R "represent, independently of one another, a saturated, unsaturated, aromatic, monocyclic or polycyclic C1-C20 carbocyclic or heterocyclic radical as defined above, provided that when Rf represents a CF3 group , Y an NH 2 group, then R 'and R "do not simultaneously represent an unsubstituted phenyl ring or R' and R" are linked together so as to constitute with the carbon atoms which carry them a carbocyclic or heterocyclic radical of 4 to 20 atoms saturated, unsaturated, aromatic, monocyclic or polycyclic, and Rf represents (i) a halogen atom, preferably fluorine, (ii) a C 1 -C 10 alkyl radical or a C 3 -C 10 cycloalkyl radical, poly halogenated, (iii) a phenyl radical substituted by at least one polyhalogenated C1 to C4 radical, (iv) a mono-, poly- or halogenated phenyl radical and - Y, L and Z are as defined above .

As more specific examples, there may be mentioned the complexes corresponding to the general formula IVb.

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 with L, Z and M as defined above.

 Of particular interest are compounds of formula IVb wherein - L represents an aromatic selected from benzene, paramethylisopropylbenzene or hexamethylbenzene, - a chlorine atom or a bromine atom, and - M a ruthenium atom.

le (1 S,2S)-N-trifluorométhanesulfonyl-1,2-cyclohexanediamine, le (1S.2S)N-trifluorométhanephénylsulfonyl-1,2-cyclohexanediamine, le (1 S,2S)-N- N-(Nonafluorobutanesulfonyl)-1,2-diphényléthylènediamine, le (1 S,2S)-N- (Nonafluorobutanesulfonyl)-1,2 cyclohexanediamine, le (1 S,2S)-N- (pentafluorophénylsulfonyl)-1,2 cyclohexanediamine, le (1 S,2S)-N-

(pentafluorophénylsulfonyl)-1,2-diphényléthylènediamine, le (1 S,2S)-N- (3,5-bis (trifluorométhane) phénylsulfonyl)1,2-cyclohexanediamine, le (1 S,2S)-N-(3,5-bis (trifluorométhane) phénylsulfonyl) 1,2diphényléthylènediamine. Of particular interest are the complexes according to the present invention having as a ligand a compound selected from

(1S, 2S) -N-trifluoromethanesulfonyl-1,2-cyclohexanediamine, (1S, 2S) N-trifluoromethanephenylsulfonyl-1,2-cyclohexanediamine, (1S, 2S) -N- N- (Nonafluorobutanesulfonyl) - 1,2-diphenylethylenediamine, (1S, 2S) -N- (Nonafluorobutanesulfonyl) -1,2-cyclohexanediamine, (1S, 2S) -N- (pentafluorophenylsulfonyl) -1,2-cyclohexanediamine, (1S, 2S )-NOT-

(1 S, 2S) -N- (3,5-bis (trifluoromethane) phenylsulfonyl) 1,2-cyclohexanediamine, (1S, 2S) -N- (3-pentafluorophenylsulfonyl) -1,2-diphenylethylenediamine; 5-bis (trifluoromethane) phenylsulfonyl) 1,2-diphenylethylenediamine.

 The present invention also provides a process for preparing said complexes comprising reacting an optically active form of a compound of general formula 1 as defined above with the selected transition metal compound in a suitable organic solvent.

 Complexes comprising as a ligand the compound of formula # above and the transition metal can be prepared according to the known methods described in the literature.

 For the preparation of ruthenium complexes, reference can be made in particular to the publication of J. -P. Broom [Acros Organics Acta, 1, Nr. 1, pp. 1-8 (1994)] and for the other complexes in the article of

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 Schrock R. and Osborn J.A. [Journal of the American Chemical Society, 93, pp. 2397 (1971)].

 The reaction is generally conducted at a temperature between room temperature (15 to 25 C) and the reflux temperature of the reaction solvent.

 As examples of organic solvents, mention may be made, inter alia, of aliphatic hydrocarbons, halogenated or not, and more particularly hexane, heptane, isooctane, decane, benzene, toluene, methylene chloride and chloroform. ; solvents of the ether or ketone type and especially diethyl ether, tetrahydrofuran, acetone, methyl ethyl ketone; alcohol type solvents, preferably methanol, ethanol or isopropanol.

 The metal complexes according to the invention, recovered according to conventional techniques (filtration or crystallization) are used in asymmetric hydrogenation reactions of substrates specified below.

 The present invention also relates to the use of a metal complex as defined above to achieve asymmetric organic synthesis and more particularly the asymmetric reduction of ketone derivatives.

 It also relates to the use of a metal complex as defined above for carrying out the enantioselective catalytic oxidation of a chiral secondary alcohol in the form of a racemic mixture.

The ketone derivatives which can be hydrogenated with a metal complex according to the invention preferably correspond to the general formula V * R1-C-R2 V #
O

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 in which - R 1 and R 2 represent, independently of each other: (i) an alkyl chain, preferably a C 1 -C 10 chain, optionally interrupted by one or more oxygen or sulfur atoms or a functional group ( s) carbonyl and optionally substituted by one or more halogen atoms or carboxyl groups, (ii) an alkenyl or alkynyl chain, preferably a C2 to C10 chain, optionally interrupted by one or more oxygen or sulfur atom (s) or carbonyl function (s) and optionally substituted by one or more halogen atom (s) or carboxyl group (s); (iii) an aryl group, preferably C6 to C12, optionally substituted with one or more halogen atoms or alkyl or alkenyl group (s); (iv) an arylalkyl group, preferably C7 to C15, optionally substituted with one or more halogen atom (s); (v) an arylalkenyl group, preferably C8 to C15, optionally substituted by one or more halogen atom (s); and - * indicates the possible presence in R2 of an asymmetric center located in position a of the carbonyl function.

 As a representative of the substituents R2 having a center of asymmetry, there may be mentioned particularly radicals R2, the carbon atom bearing the center of asymmetry is substituted by a mono- or disubstituted amine function and by an ester function.

 Advantageously, the use of a complex according to the invention for reducing a racemic mixture of ketonic derivatives of this type, that is to say having a ketonic function at a center of asymmetry, makes it possible to obtain the hydroxylated derivative. corresponding by controlling the stereochemistry of two centers of asymmetry. We are witnessing a dynamic kinetic resolution of the whole molecule.

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The process of the invention is particularly applicable to the preparation of an optically active hydroxyl compound of general formula VI
OH (VI)
R1-C-R2
In which: R 1 and R 2 represent, independently of one another, (i) an alkyl chain, preferably a C 1 to C 10 chain, optionally interrupted by one or more oxygen or sulfur atom (s) or a function (s) carbonyl and optionally substituted by one or more halogen atoms or carboxyl groups, (ii) an alkenyl or alkynyl chain, preferably a C2 to C10 chain, optionally interrupted by one or more oxygen atom (s) or sulfur or carbonyl function (s) and optionally substituted by one or more halogen atom (s) or carboxyl group (s); (iii) an aryl group, preferably a C6-C12 group, optionally substituted by one or more atoms or alkyl or alkenyl group (s); (iv) an arylalkyl group, preferably C7 to C15, optionally substituted with one or more halogen atom (s); (v) an arylalkenyl group, preferably C8 to C15, optionally substituted by one or more halogen atom (s), and - * indicates the presence of a center of chirality at the carbon, characterized in that it implements the asymmetric reduction of a compound of general formula V * R1-C-R2 C (V)
0 as defined above

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 in the presence of a metal complex whose transition metal has as ligand at least one optically active form of a compound of general formula 1 as defined above.

 Preferably, the complex corresponds to one of the formulas IV specified above.

 According to a preferred variant of the invention, the complex is generated in situ in the reaction medium of the catalytic reduction according to the method mentioned above. It is only after the complex has been prepared that the ketone derivative of formula V to be treated is added to said medium.

 The selective asymmetric reduction of said substrate of formula V is carried out thus using as catalyst a metal complex according to the invention, that is to say, liganded by an optically active derivative of general formula I.

 The reduction of the ketone derivative is generally carried out at a temperature of between 5 ° C. and 100 ° C. in the presence of a hydrogen donor.

 As is apparent from the examples below, it is possible to significantly accelerate the kinetics of the reaction by increasing the temperature of the reaction medium without impairing the enantiomeric yield.

Accordingly, those skilled in the art are able to set the proper temperature range to achieve the best compromise between reaction rate and enantiomeric efficiency. Generally, this temperature is between 20 C and 50 C.

 The hydrogen donor is conventionally represented by a lower secondary alcohol or a mixture of formic acid and tertiary amine.

Generally, this hydrogen donor is used as a solvent. As a representative of lower secondary alcohols, there may be mentioned 2- or 3-butanol and isopropanol.

 The complex based on the compound of general formula 1 and on the transition metal is used in a proportion of 1/10000 to 1/1 moles relative to the carbonyl compound of general formula V. It appears that the increase

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 the catalyst / substrate ratio does not have a significant impact on the enantioselectivity of the reduction.

 The reaction is preferably carried out in an organic co-solvent. Any solvent is used as long as it is stable under the operating conditions. It is preferable to use a polar organic solvent such as dichloromethane.

 The concentration of the substrate in the solvent advantageously varies between 0.01 and 3 moles per liter.

 A basic compound may optionally be added during the reaction. This basic compound may be an alkaline base such as sodium or potassium hydroxide or a primary, secondary or tertiary amine, and more particularly pyridine, pyperidine, triethylamine, and preferably triethylamine. It activates the catalyst by generating the corresponding metal hydride.

 As mentioned above, the use of the compounds of general formula # as ligands makes it possible to significantly improve the enantiomeric excess and the kinetics in certain asymmetric reactions, in particular in the hydrogenation reactions of ketonic functions in secondary alcohols.

 The examples which appear below are presented as non-limiting illustrations of the present invention.

EXAMPLE 1
Trifluoromethanesulfonylation of diaminocyclohexane

 In a three-necked flask of 100 ml, equipped with an addition funnel, a temperature probe and a magnetic stir bar with agitation by a magnetic stirrer.

 Charge: - 4.82 g of (1S, 2S) -1,2-cyclohexanediamine, - 7,11 g of trifluoromethanesulfonyl chloride, and - 40 ml of dichloromethane.

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 The first step is to charge the diamine and dichloromethane and then establish an atmosphere of inert gases (nitrogen). The reaction mixture is cooled to a temperature of 3 C with the aid of an ice bath. The sulfonylating agent is slowly charged (30 min) by means of an addition funnel. The reaction mixture is allowed to rise to room temperature (22 ° C.) with stirring for two hours and then the precipitate formed filtered. It is rinsed with diethyl ether. The product is dried under vacuum.

 9.24 g of a white solid corresponding to ammonium chloride (1S, 2S) -N-trifluoromethanesulfonyl-1,2cyclohexanediamine is recovered, which corresponds to a yield of 74%.

 In a 100 ml Erlenmeyer flask, 3.99 g of the solid and 15 ml of distilled water are charged. The pH of this aqueous phase is adjusted to between 7 and 8 by addition of a 2M aqueous solution of sodium hydroxide. It is left for 16 hours at room temperature. The crystallized product is filtered. It is dried under vacuum. 1.78 g of (1S, 2S) -N-trifluoromethanesulfonyl-1,2cyclohexanediamine are recovered in a yield of 51%.

EXAMPLE 2 Trifluoromethanephenylsulfonylation of diaminocyclohexane

 In a 10 ml flask are charged: 50 mg of (1S, 2S) -1,2-cyclohexanediamine, 89 mg of 4-trifluoromethane-phenylsulfonyl chloride, 4.5 ml of dichloromethane.

 The first step is to charge the diamine and dichloromethane and then establish an atmosphere of inert gases (nitrogen). The reaction mixture is cooled to a temperature of 3 C with the aid of an ice bath. 4-Trifluoromethane-phenylsulfonyl chloride is added slowly using a syringe. The reaction mixture is stirred at room temperature for 5 hours. It is diluted with 5 ml of dichloromethane and the solution is then washed with a saturated aqueous solution of NaHCO 3 (8 ml)

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 then dried over Na2SO4. After evaporation of the solvent, 102 mg of a white powder corresponding to (1S, 2S) -N- (4-trifluoromethanephenylsulfonyl) -1,2-cyclohexanediamine are recovered, which corresponds to a yield of 88%.

EXAMPLE 3 Trifluoromethanesulfonylation of 1,2-diphenylethylenediamine

 In a three-necked flask of 100 ml, equipped with an addition funnel, a temperature probe and a stir bar with agitation by a magnetic stirrer, the following are charged: - 4.97 g of (1S, 2S ) -1,2-diphenylethylenediamine, 3.94 g of trifluoromethanesulfonyl chloride, and 30 ml of dichloromethane.

 The first step is to charge the diamine and dichloromethane and then establish an atmosphere of inert gases (nitrogen). The reaction mixture is cooled to a temperature of 3 C with the aid of an ice bath. The sulfonylating agent is slowly charged (30 min) by means of an addition funnel. The reaction mixture is allowed to rise to ambient temperature (22 ° C.) with stirring for two hours and the white precipitate formed filtered off. 20 ml of dichloromethane are added and the organic phase is then washed with a 2M aqueous solution of HCl and with water saturated with NaCl. The organic phase is concentrated and then the white solid formed is filtered off. The white solid is dried under vacuum.

 1.8 g of (1 S, 2S) -N-trifluoromethanesulfonyl-1,2-diphenylethylenediamine are recovered.

EXAMPLE 4 Reduction of Acetophenone

 As a reducing medium, a mixture composed of:

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- (1 S,2S)-N-trifluorométhanesulfonyl-1,2-cyclohexanediamine. isopropanol / KOH - [RuCl2 (p-cymene)] 2

(1S, 2S) -N-trifluoromethanesulfonyl-1,2-cyclohexanediamine.

 In a 250 ml flask equipped with a condenser, a stir bar and stirring with a magnetic stirrer, the following are charged: - 10 mmol of acetophenone - 5.10 -2 mmol of [RuCl 2 (p-cycmene)] - 0.1 mmol of (1S, 2S) -N-trifluoromethanesulfonyl-1,2-cyclohexanediamine - 0.25 mmol of KOH and - 100 ml of isopropanol.

 The ruthenium complex, the ligand and 20 ml of isopropanol are first charged and then an argon atmosphere is established. The reaction medium is heated at a temperature of 80 ° C. for 30 minutes. 80 ml of isopropanol, potassium hydroxide and acetophenone are then charged. The reaction mixture is left stirring for 72 hours at 22 ° C. The product formed, namely 1-phenylethanol and the enantiomeric excess is determined by gas chromatography.

 68% of 1-phenylethanol is obtained with an enantiomeric excess of 82% in favor of the S-isomer.

EXAMPLES 5 AND 6 Reduction of acetophenone.

- le (1 S,2S)-N-trifluorométhanesulfonyl-1,2-cyclohexanediamine ou le (1 S,2S)-N-trifluorométhanesulfonyl-1,2-diphényléthylènediamine comme ligand chiral. The reducing medium used is: an azeotropic mixture of formic acid and triethylamine [RuCl 2 (p-cymene)] 2 as the metal complex and

(1S, 2S) -N-trifluoromethanesulfonyl-1,2-cyclohexanediamine or (1S, 2S) -N-trifluoromethanesulfonyl-1,2-diphenylethylenediamine as a chiral ligand.

 In a 25 ml flask fitted with a magnetic stir bar with agitation by a magnetic stirrer, the following are charged:

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 10 mmol of acetophenone - 0.05 mmol of [RuCl2 (p-cymene)] 2 - 0.1 mmol of ligand - 2 ml of formic acid - 3 ml of triethylamine.

 The ruthenium complex, the ligand and 10 ml of isopropanol are charged first. An argon atmosphere is established and the reaction medium is heated at a temperature of 80 ° C. for 30 minutes. The solvent is evaporated under reduced pressure and a red solid is obtained.

 In another 25 ml flask, cooled by an ice bath and provided with a magnetic bar with stirring by a magnetic stirrer, 3 ml of triethylamine, 2 ml of formic acid and 10 mmol of acetophenone are charged. The reaction mixture is purged with argon and then this solution is transferred to the flask containing the catalyst.

 The reaction mixture is left at room temperature (22 ° C.) with stirring. The duration of the reaction is mentioned in the table below.

 The formed product, namely (1S) -1-phenylethanol, is determined by gas chromatography.

The results obtained are recorded in Table 1 below:
This table also accounts for the reduction of acetophenone in the presence of a ligand not according to the present invention, (1S, 2S) -N-tosyl-1,2-cyclohexanediamine.

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Exemple ligand durée Rendement e.e. Table 1

Example ligand duration Yield ee

H .NHSOzCFg 5 jY | 72 h 85% 91% NH 2 Ph H Ph H NHSO 2 CCF 3 45 h 99% 93% Ph H NH 2 Control H NHSO 2 - (J CH 3 38 h 1% H NH 2
It is noted that only the ligands bearing fluorine atoms on the carbon at the sulfonyl group are effective.

EXAMPLES 7 AND 8 Acetophenone reduction.

 The same reducing medium as in Example 5 is used, the procedure of which is reproduced by modifying the temperature.

 The results are recorded in the following table:

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Table 2

<Tb>
<tb> Example <SEP> Temperature <SEP> Time <SEP> Yield <SEP> ee
<Tb>

7 <SEP> 5 C <SEP> 15 <SEP> days <SEP> 27% <SEP> 92 <SEP>% <SEP>
<tb> 8 <SEP> 50 C <SEP> 5 <SEP> h <SEP> 99% <SEP> 88%
<Tb>

It is possible to increase the reaction rate by heating the reaction medium without impairing the enantiomeric yield.

EXAMPLE 9 Reduction of Acetophenone

 The same reducing medium as in Example 5 is used, the procedure of which is reproduced by modifying the substrate / catalyst ratio.

 The reduction is therefore carried out on 1 mmol of acetophenone instead of 10 mmol in Example 5, keeping everything else equal.

 99% of the 1-phenylethanol is obtained after 21 hours at 22 ° C. with an enantiomeric excess of 92% in favor of the S-isomer.

 It appears that the increase of the catalyst / substrate ratio does not have a significant impact on the enantioselectivity of the reduction.

EXAMPLES 10 AND 11 Acetophenone reduction.

 The same reducing medium as in Example 5 is used, the procedure of which is reproduced but the nature of the complex is modified.

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 metallic. The retained complex is ligated with (1S, 2S) N-trifluoromethanesulfonyl-1,2-cyclohexanediamine.

Ref Complexe Durée Rendement e.e. Table 3

Complex Ref Duration Performance ee

Metallic Ex. 10 [Cp + 1 Cl 2 96h 52 90 11 [Cp'RhCh] 2 72 h 86 89 5 [RuCl 2 (p-cymene)] 72 h 85
The results are comparable in terms of enantioselectivity.

EXAMPLES 12 AND 13 Reduction of 3 ', 4'-dimethoxyacetophenone.

 The same reducing medium as in Example 5 is used, the procedure of which is reproduced using either the ligand prepared in Example 1 or the ligand prepared in Example 3.

 The duration is mentioned in the table below. The formed product, namely (R) -3 ', 4'-dimethoxy-1-phenylethanol, is determined by high performance liquid chromatography.

 The results obtained are shown in Table 4 below:

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Ref Ligand Rendement e.e. ex. Table 4

Ref Ligand Yield ee ex.

H 12 NHS02CF3 93% 75% NH2 Ph NHSO2CF3 87% 13 NHSOCFs 87% 80% Ph H = NH2 EXAMPLE 14 Preparation of p-keto-α-amino acid derivatives 1a, 1b.

The ss-ketonic- [alpha] -amino acid derivatives used are as follows:

Preparation of methyl (3,4-dimethoxyphenyl) -2- (benzoyloxycarbonyl) methylamino-3-oxopropanoate (1a)

 To LHMDS lithium hexamethyldisilazane cooled to -78 ° C (1.06 M in THF, 2 equivalents) is added a solution of Cbz-Sar-Ome

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 (1 equivalent, 0.5 g / ml in THF), in THF. After stirring for 1 hour, a solution of 3,4-dimethoxybenzoic acid chloride (1 eq., 0.5 g / ml THF) is added via a cannula. The reaction medium is stirred for 30 min, poured into a saturated aqueous solution of NH4Cl and extracted with EtOAc. The organic phase is dried with sodium chloride solution followed by MgSO4H2O. By concentration an amber colored syrup is obtained in a quantitative yield.

 1 H NMR (300 MHz, CDCl 3): # 2. 84-2.86 (m, 3H, Nme), 3.62-3.91 (m, 9H, CO 2 Me, 2xOMe), 5. 13-5.14 (m, 2H, CH 2 Ph) , 6.12 and 6. 40 (2s, 0.8H, CH keto), 6. 58-7.62 (m, 8H, CH 2 Ph).

 Preparation of methyl (3,4-dimethoxyphenyl) -2- (benzoyloxycarbonyl) methylamino-3-oxopropanoate (1b).

 The ketone amino acid 1b is prepared from 3,4-dimethoxybenzoic acid chloride according to the protocol described for the derivative 1a. The concentrated residue is then purified by chromatography (eluent: hexane / EtOAc 3: 1, then 2: 1) and crystallized (hexane / EtOAc) to give a yield of 60% derivative 1b.

 1 H NMR (300 MHz, CDCl 3): δ 3.62 and 3.74 (2 br s, 3H, CO2Me), 3.94 and 3.98 (2s, 6H, 2xOMe), 5. (s, 2H, CHPh), 5. 97 and 6. 00 (d, 1.9H, CH keto, J = 7.9Hz), 6. and 22 (d, 0.9H, NH, J = 7.9Hz), 6. 94-7.83 (m, 8H, C6H3CH2Ph).

EXAMPLE 15 Asymmetric hydrogen transfer hydrogenation of p-keto-α-amino acid derivatives using chiral Ru (II) complexes.

 The general protocol implemented is as follows: [RuCl 2 (p-cym)] 2, and chiral diamine (1.5 equivalents relative to Ruthenium atom) are stirred in iso-propanol (1 ml, dry ) at 80-

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 85 C for 3 hours under argon. After cooling to room temperature, the ketonic amino acid (1 mmol) in dichloromethane (1 ml distilled over CaH 2) and a mixture of formic acid triethylamine (5: 2.1 ml) were added consecutively. Stirring is maintained at 50 ° C. at the time indicated in Table 5. The reaction medium is then extracted with ethyl acetate (15 ml) in the presence of a saturated solution of sodium bicarbonate (15 ml). The organic phase is then washed with sodium chloride solution (15 ml), dried over MgSO 4 and concentrated in order to yield the hydroxy derivative of the expected amino acid.

 The threo-2a and erythro-2a derivatives obtained at the end of the catalytic hydrogenation are characterized by NMR: methyl threo- (3,4-dimethoxyphenyl) -2 - [(benzoyloxycarbonyl) methylamino] -3-hydroxypropanoate (threo -2a).

e rythro-(3 ,4-dimétoxyp hényl)-2-[ (be nzoyloxycarbonyl )méthylami no]- 3-hydroxypropanoate de méthyle (erythro-2a). 1 H NMR (300 MHz, CDCl 3): # 2. 92 and 3. 08 (2 br s, 3H, Nme), 3.69-3.91 (m, 9H, CO2Me, 2xOMe), 4.71-5.39 (m, 4H, CHN, CHPh, CHOH), 6.83-6.93 (m, 3H, C6H3), 7. 15-7.35 (m, 5H, CH2Ph).

Methyl (3, 4-dimetoxypenyl) -2- [(benzoyloxycarbonyl) methylamino] - 3-hydroxypropanoate (erythro-2a).

 1H NMR (300MHz, CDCl3): δ 2. 58 and 2.60 (2 br s, 3H, NMe), 3.65 and 3.74 (2s, 3H, CO2Me), 3.80 and 3. 87 (2s, 6H, 2xOMe), 4. 08-4.17 (m, 1H, CHN), 4.71 (bs, 1H, OH), 5. 04-5.26 (m, 3H, CH 2 Ph, CH 2 OH), 6. 72-6.92 (m, 3H, C 6 H 3), 7. 24-7.39 (m, 5H, CH 2 Ph).

The compounds 2a, b (0.5 mmol) are then deprotected according to the following protocol:
They are stirred with 10% Pd-C (15 mg) and HC02NH4 (0.13 g, 4 eq) in methanol overnight. The mixture is then filtered on Celite,

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 concentrated, and extracted with dichloromethane (10 mL) in the presence of saturated sodium chloride solution (5 mL) and saturated aqueous NaHCO3 (2 mL). The organic phase is dried (Na2SO4) and concentrated to yield about 95% of 2a, b. Before the determination of the enantiomeric excess by HPLC on a Chiralpack AD column, the sample is purified on PLC plate (CH 2 Cl 2 / EtOH 40: 1).

 The products thus obtained are characterized by NMR.

 Methyl threo- (3,4-dimethoxyphenyl) -N-methylserine (threo-2a) ester.

 1 H NMR (300 MHz, CDCl 3): # 2.41 (s, 3H, Nme), 3.20 (d, 1H, CHN, J = 7.9Hz), 3. 56 (s, 3.56 (s)). , 3H, CO2Me), 3. 87 and 3. 89 (2s, 6H, 2xOMe), 4. 53 (d, 1H, CHO: J = 7.9Hz), 6. 82-6.92 (3H, m, C6H3) .

 Methyl erythro- (3,4-dimethoxyphenyl) -N-methylserine ester (erythro-2a).

 1 H NMR (300 MHz, CDCl 3): # 2. 42 (s, 3H, Nme), 3. 53 (d, 1H, CHN, J = 5.7Hz), 3.69 (s, 3H, CO 2 Me 3.87 and 3.88 (2s, 6H, 2xOMe), 4.93 (d, 1H, CH = J = 5.7Hz), 6. 76-6.84 (3H, m, C6H3).

 Table 5 below shows the operating conditions in terms of time and substrate / catalyst ratio retained for each chiral ligand tested and yields of hydroxyl derivatives obtained as well as enantiomers.

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Conditions produits essai substrat diamine chirale S/C Temps, conv., threo %eeC h %a erythro b 1 la ((-.0- 40 96 25 97/3 72 NI-!: 2 1 a 50 40 95 65 95/5 94 Hso,-j)#cr, 3 la ph 'Nçp2 40 62 75 95/5 82 Ph 'NHZ 4 la , ,,,NHSOZCF3 40 72 >95 95/5 98 NHZHCI d 5 .,,NHS02CF3 40 100 88/12 NHS02CF3 40 100 88/12 NH2HCI 6 la Ph ,,NHSOZCF3 40 35 100 95/5 99 Ph NH2 7 lb ,,NHSOzCF3 40 42 100 94/4 NH2HCI 8 lb Ph X ,.NHSÜ:!CF3 40 15 100 92/8 Ph NH2 Table 5

Test conditions test substrate diamine chiral S / C Time, conv., Threo% eeC h% a erythro b 1 la ((-.0- 40 96 25 97/3 72 NI- !: 2 1 to 50 40 95 65 95 / ## STR6 ## wherein: ## STR2 ## wherein: ## STR2 ## ## STR5 ## wherein: Ph.sub.2 NH.sub.2 SO.sub.4 CF.sub.3. / 8 Ph NH2

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 Estimated by 1H-NMR analysis Determined by 1H-NMR analysis at 300 MHz of deprotected compound 3 Determined by HPLC analysis using a Chiralpack AD column [RuCl2 (benzene)] was used.

 It is noted that the enantioselectivity is lower when the chiral ligands are not in accordance with the invention (tests 1 and 3).

 In addition, it is necessary to significantly extend the reaction over time for these two tests in order to obtain a significant enantiomeric yield.

EXAMPLE 16 Catalytic Oxidation Using Ruthenium Complexes According to the Invention

The oxidation is carried out according to the following reaction scheme:

In a 25 ml monocolon, the ruthenium complex (31 mg, 0.05 mmol), the ligand (2 eq) in solution in 10 ml of isopropanol are introduced. The reaction medium is heated at 80 ° C. under an argon atmosphere for 3/4 of an hour. It is concentrated to dryness on a rotary evaporator and then the racemic alcohol 3a-3b (1. 2 g, 10 mmol, 200 eq.) And the solvent (5 ml) are introduced. The mixture is then degassed by bubbling argon for an hour and then the powdered potash (14 mg, 0.25 mmol, 5 eq.) Is added. The medium is stirred under an argon atmosphere at 30 ° C.

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 The reaction is monitored by GC: column CYCLODEX B 236M 25mx0.25m; initial temperature of the column 100 C; final temperature of the column 150 C; rate 2 C / min. ; temperature of the injector 150 C; detector temperature 240 C; volume injected 2 l; Retention time of cyclopentanone = 2.25 min, cyclopentanol = 2.6 min. n acetophenone 5 = 6. 6min., 4 = 9. 2min., 3 = 9. 8 min.

 By TLC: eluent petroleum ether / ethyl acetate 95/5; UV developer; Rf acetophenone = 0.44; Rfphenyl ethanol = 0.28.

1) Test with a Chiral Ligand: The first ligand corresponds to the following formula:

This test is carried out in acetone. The reaction medium is orange and becomes brown during the reaction. After 6 hours at 30 ° C., 50% of 4 and an enantiomeric excess of 64% in favor of alcohol 3b are obtained as a percentage surface area.

 By resuming this test in cyclopentanone, a red reaction mixture is obtained which becomes brown during the reaction. After 6 hours at 30 ° C., 44% of 4 and an enantiomeric excess of 52% in favor of alcohol 3b are obtained as a percentage surface area.

The second ligand has the following formula:
Ph HH @ Ph
H2N NHSO2CF3

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A first test carried out in acetone leads to a pink reaction medium. After 5 hours at 30 ° C., 53% of 4 and an enantiomeric excess of 85% in favor of the alcohol 3b are obtained as a surface percentage.

 The same test carried out in cylopentanone leads to a red reaction medium. After 5 hours at 30 ° C., 41% of 4 and an enantiomeric excess of 85% in favor of alcohol 3b are obtained as a percentage surface area.

(1 S,2S)-N-(Nonafluorobutanesulfonyl)-1,2-diphényléthylènediamine
A une solution de (1S,2S)-1,2-diphényléthylènediamine (100 mg, 0,47 mmol) et de 4-diméthylaminopyridine (57 mg, 0,47 mmol) dans l'acétonitrile (5 ml), on ajoute du fluorure de nonafluorobutanesulfonyle (100 l, 0,56 mmol). Après agitation une nuit entière, une nouvelle partie de fluorure de nonafluorobutanesulfonyle est ajoutée (100 ln 0,56 mmol). EXAMPLE 17

(1S, 2S) -N- (Nonafluorobutanesulfonyl) -1,2-diphenylethylenediamine
To a solution of (1S, 2S) -1,2-diphenylethylenediamine (100 mg, 0.47 mmol) and 4-dimethylaminopyridine (57 mg, 0.47 mmol) in acetonitrile (5 mL) is added nonafluorobutanesulfonyl fluoride (100 l, 0.56 mmol). After stirring overnight, a new portion of nonafluorobutanesulfonyl fluoride is added (100 ln 0.56 mmol).

The mixture is added one day, concentrated and extracted between water (10 ml) and ethyl acetate (20 ml). The organic phase is dried (Na 2 SO 4) and concentrated to obtain a mixture of the starting material and the final product. Purification was carried out by chromatography (EtOAc / MeOH 40. 1) followed by treatment with ether to obtain a compound in crystalline form (115 mg, 49%).

 1 H NMR (300 MHz, CDCl 3): 4.41 (d, 1H, CHNH 2, J = 3.0 Hz), 4.76 (d, 1 H, CHNH, J = 3.0 Hz), 7, 38 (m, 10H, 2 x Ph).

EXAMPLE 18 Asymmetric hydrogenation using a ruthenium complex comprising as ligand the compound of Example 17.

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 [RuCl 2 (p-cymene)] 2 (12.5 mol) and (1S, 2S) -N- (nonafluorobutanesulfonyl) -1,2-diphenylethylenediamine (30 mol, 1.2 eq per ruthenium atom) are stirred in isopropanol (1 ml) at 80 ° C. for 2 hours. Methyl oxopropanoate 2 - [(benzyloxycarbonyl) methylamino] -3- (3,4-dimethoxyphenyl) (0.40 g, 1 mmol) in dichloromethane (1 ml) and HC02H-Et3N (5.2 ml) ) are then successively added at room temperature. Stirring is maintained at 45 ° C for 27 hours to obtain 10% conversion. The reaction mixture is then extracted between ethyl acetate and a saturated solution of NaHCO 3, the organic phase is washed with sodium chloride solution, dried (MgSO 4) and concentrated.

1 H NMR (300 MHz, CDCl 3): threo / erythro = 95.5.

 EXAMPLE 19 (1S.2S) -N- [3,5-Bis (trifluoromethane) phenylsulfonyl] -1,2-cyclohexanediamine.

In a 50 ml three-necked flask, equipped with an addition funnel, a temperature probe and a magnetic bar with agitation by a magnetic stirrer:
Charge: -0.50 g of (1 S, 2S) -1,2-cyclohexanediamine, -1. 37 g of 3,5-bis (trifluoromethane) phenylsulfonyl chloride, and -20 ml of dichloromethane.

 The sulphonyl chloride and dichloromethane are initially charged and an atmosphere of inert gases (nitrogen) is established.

The reaction mixture is cooled to a temperature of 3 C with the aid of an ice bath. The diamine dissolved in dichloromethane (10 ml) is slowly charged (time 10 min) by means of an addition funnel. The reaction mixture is allowed to rise to ambient temperature (22 ° C.) with stirring for two hours. The reaction medium is diluted with

<Desc / Clms Page number 39>

au (1 S,2S)-N-[3,5-bis(trifluorométhyl)benzènesulfonyl]-1,2- cyclohexanediamine. 30 ml of dichloromethane and then washed with 10 ml of HCl (2M). The aqueous phase is adjusted to a pH between 7 and 8 by adding a 2M aqueous solution of sodium hydroxide and then extracted with 2 × 25 ml of dichloromethane. The organic phase is dried over Na 2 SO 4 and then evaporated under vacuum. 330 mg of a corresponding white solid is recovered

(1S, 2S) -N- [3,5-bis (trifluoromethyl) benzenesulfonyl] -1,2-cyclohexanediamine.

 EXAMPLE 20 (1S, 2S) -N- [3,5-Bis (trifluoromethane) benzenesulfonyl] 1,2-diphenylethylenediamine.

In a 50 ml three-necked flask, equipped with an addition funnel, a temperature probe and a magnetic bar with agitation by a magnetic stirrer:
Charge: -2 g of (1S, 2S) -1,2-diphenylethylenediamine, -2. 94 g of 3,5-bis (trifluoromethyl) benzenesulfonyl chloride, and -25 ml of dichloromethane.

 The first step is to charge the diamine and dichloromethane (20 ml) and then establish an atmosphere of inert gases (nitrogen). The reaction mixture is cooled to a temperature of 3 C with the aid of an ice bath. The sulphonyl chloride in solution in dichloromethane (5 ml) is slowly charged (duration 10 min) by means of an addition funnel. The reaction mixture is allowed to rise to ambient temperature (22 ° C.) with stirring for two hours and then the solid formed is filtered. The solid is dissolved in dichloromethane (50 ml) and this organic phase is washed with distilled water (10 ml). The organic phase is dried over Na 2 SO 4 and then evaporated under vacuum. 2. 2 g of a white solid corresponding to (1S, 2S) -N- [3,5-bis (trifluoromethyl) benzenesulfonyl] -1,2-diphenylethylenediamine are recovered.

<Desc / Clms Page number 40>

EXAMPLE 21 (1S, 2S) -N- (pentafluorobenzenesulfonyl) 1,2-cyclohexanediamine

In a tricolor of 50 ml, equipped with a temperature probe and a magnetic bar with agitation by a magnetic stirrer:
Charge: 0.50 g of (1S, 2S) -1,2-cyclohexanediamine, -650 l of pentafluorobenzenesulfonyl chloride, and -10 ml of dichloromethane.

 The first step is to charge the diamine and dichloromethane and then establish an atmosphere of inert gases (nitrogen). The reaction mixture is cooled to a temperature of 3 C with the aid of an ice bath. The sulfonyl chloride is slowly charged (duration 5 minutes) by means of a syringe. The reaction mixture is allowed to rise to ambient temperature (22 ° C.) with stirring for two hours. The reaction medium is diluted with 30 ml of dichloromethane and then washed with 10 ml of HCl (2M). The aqueous phase is then adjusted to a pH between 7 and 8 by adding a 2M aqueous sodium hydroxide solution and then extracted with 2 × 25 ml of dichloromethane. The organic phase is dried over Na 2 SO 4 and then evaporated under vacuum. 250 mg of a white solid corresponding to (1S, 2S) -N-pentafluorobenzenesulfonyl-1,2cyclohexanediamine are recovered.

(1S,2S)-N-(pentafluorobenzènesulfonyl)1,2-diphényléthyIènediamine. EXAMPLE 22

(1S, 2S) -N- (pentafluorobenzènesulfonyl) 1,2-diphényléthyIènediamine.

In a 50 ml three-necked flask, equipped with an addition funnel, a temperature probe and a magnetic bar with agitation by a magnetic stirrer:
We charge:

<Desc / Clms Page number 41>

 -2. 15 g of (1S, 2S) -1,2-diphenylethylenediamine, -500 l of pentafluorobenzenesulfonyl chloride, and -25 ml of dichloromethane.

 The first step is to charge the diamine and dichloromethane (20 ml) and then establish an atmosphere of inert gases (nitrogen). The reaction mixture is cooled to a temperature of 3 C with the aid of an ice bath. The sulphonyl chloride in solution in dichloromethane (5 ml) is slowly charged (duration 30 min) by means of an addition funnel. The reaction mixture is allowed to rise to ambient temperature (22 ° C.) with stirring for two hours and then the solid formed is filtered. The organic phase is washed successively with 5 ml of HCl (2M) and 5 ml of a saturated aqueous solution of NaCl, dried over Na 2 SO 4 and then evaporated under vacuum. 1. 01 g of a white solid corresponding to the ammonium chloride of (1S, 2S) - / V- pentafluorobenzene sulfonyl-1,2-diphenylethylenediamine are recovered.

EXAMPLE 23 (1S, 2S) -N- (nonafluorobutanesulfonyl) 1,2-cyclohexanediamine

In a 50 ml three-necked flask, equipped with an addition funnel, a temperature probe and a magnetic bar with agitation by a magnetic stirrer:
We charge: -1. 0 g of (1S, 2S) -1,2-cyclohexanediamine, -3. 5 ml of nonafluorobutanesulfonyl fluoride, -6. 9 ml of diisopropylethylamine, and -15 ml of dichloromethane.

 The first step is to charge the diamine and dichloromethane (20 ml) and then establish an atmosphere of inert gases (nitrogen). The reaction mixture is cooled to a temperature of 3 ° C. with the aid of a bath of

<Desc / Clms Page number 42>

 ice cream. The base is then loaded slowly (duration 10 min) sulfonyl fluoride. The reaction mixture is allowed to rise to ambient temperature (22 ° C.) with stirring for six hours. The reaction medium is diluted with diethyl ether (50 ml) and then washed successively with 3 × 10 ml of HCl (2M) and 5 ml of a saturated aqueous solution of NaCl. The organic phase is then dried over Na 2 SO 4 and then evaporated under vacuum.

The residue obtained is crystallized from diethyl ether and 0.70 g of a white solid corresponding to ammonium chloride (1S, 2S) -A / - nonafluorobutanesulfonyl-1,2-cyclohexane diamine is recovered.

EXAMPLE 24 Acetophenone reduction.

 The reducing medium used is: azeotropic mixture of formic acid and triethylamine [RuCl 2 (p-cymene)] 2 as the metal complex and (1S, 2S) -N- (3,5-bis ( trifluoromethane) benzenesulfonyl) 1,2 cyclohexane diamine: ligand 1,1 (1S, 2S) -N- (3,5-bis (trifluoromethane) benzenesulfonyl) 1,2-diphenylethylene diamine: ligand 2, - (1S, 2S) -N- (pentafluorobenzenesulfonyl) -1,2-cyclohexane diamine: ligand 3, - (1S, 2S) -N- (pentafluorobenzenesulfonyl)) 1,2-diphenylethylene diamine: ligand 4, and - (1S, 2S) -N- (nonafluorobutanesulfonyl) 1,2 cyclohexane diamine: ligand 5. as chiral ligands.

 In a 25 ml flask fitted with a stir bar with agitation by a magnetic stirrer, the following are charged: 10 mmol of acetophenone - 0.05 mmol of [RuCl 2 (p-cymene)] 2 - 0.1 mmol of the ligand under consideration

<Desc / Clms Page number 43>

 - 2 ml of formic acid - 3 ml of triethylamine.

 The ruthenium complex, the ligand and 10 ml of isopropanol are charged first. An argon atmosphere is established and the reaction medium is heated at a temperature of 80 ° C. for 30 minutes. The solvent is evaporated under reduced pressure and a red solid is obtained.

 In another 25 ml flask, cooled by an ice bath and provided with a magnetic bar with stirring by a magnetic stirrer, 3 ml of triethylamine, 2 ml of formic acid and 10 mmol of acetophenone are charged. The reaction mixture is purged with argon and then this solution is transferred to the flask containing the catalyst.

 The reaction mixture is left at room temperature (22 ° C.) with stirring. The duration of the reaction is mentioned in the table below.

 The formed product, namely (1S) -1-phenylethanol, is determined by gas chromatography.

The results obtained are shown in Table 6 below:
Table 6

<Tb>
<tb> ligand <SEP> Time <SEP> Yield <SEP> ee
<Tb>

1 <SEP> 94 <SEP> h <SEP> 91 <SEP>% <SEP> 95%
<tb> 2 <SEP> 48 <SEP> h <SEP> 98 <SEP>% <SEP> 97 <SEP>% <SEP>
<tb> 3 <SEP> 96h <SEP> 57% <SEP> 91 <SEP>%
<tb> 4 <SEP> 25 <SEP> h <SEP> 99 <SEP>% <SEP> 97 <SEP>% <SEP>
<tb> 5 <SEP> 72 <SEP> h <SEP> 99 <SEP>% <SEP> 93 <SEP>% <SEP>
<Tb>
It is noted that all the ligands tested leads to a satisfactory ee.

<Desc / Clms Page number 44>

EXAMPLE 25 Reduction of 3 ', 4'-dimethoxyacetophenone

 The same reducing medium as in Example 24 is used, the procedure of which is reproduced using either ligand 1 or ligand 2.

 The duration is mentioned in the table below. The formed product, namely (R) -3 ', 4'-dimethoxy-1-phenylethanol, is determined by high performance liquid chromatography.

The results obtained are shown in Table 7 below:
Table 7

<Tb>
<tb> Ligand <SEP> time <SEP> Yield <SEP> ee
<Tb>

<SEP> h <SEP> 85 <SEP>% <SEP> 91 <SEP>% <SEP>
<tb> ligand <SEP> 1 <SEP> of <SEP> example <SEP> 24
<tb> 8 <SEP> h <SEP> 88% <SEP> 91 <SEP>% <SEP>
<tb> ligand <SEP> 2 <SEP> of <SEP> example <SEP> 24
<Tb>
EXAMPLE 26 Reduction of ethyl benzoylacetate

 The same reducing medium is used as Example 24, the procedure of which is reproduced using the ligand prepared in Example 1, namely (1S, 2S) -N- (trifluoromethanesulfonyl) -1,2 cyclohexanediamine, or ligand 2 of Example 24.

 The duration is mentioned in the table below.

 The results obtained are shown in Table 8 below:

<Desc / Clms Page number 45>

Table 8

<Tb>
<tb> Ligand <SEP> Time <SEP> Yield <SEP> ee
<Tb>

8 <SEP> h <SEP> 57% <SEP> 73%
<tb> ligand <SEP> of <SEP> example <SEP> 1
<tb> 72h <SEP> 67% <SEP> 95%
<tb> ligand <SEP> 2 <SEP> of <SEP> example <SEP> 24
<Tb>

Claims (33)

 in which - B represents (i) -CO-, or (ii) -SO2-, - Rf represents (i) a halogen atom, preferably fluorine, (ii) an alkyl radical preferably of C1 to C12 or C 3 to C 12 cycloalkyl, mono-, poly- or perhalogenated, the haloalkyl chain of which is optionally interrupted by one or more oxygen or sulfur atom (s), (iii) an aryl radical, preferably C C12, substituted with at least one halogenated alkyl radical as defined in (ii), (iv) an aryl radical, mono-, poly- or perhalogenated, preferably C6-C12, or (v) a radical selected from RA-CF2, -RA-CF2-CF2-, RA-CF2-CF (CF3) -, CF3-C (RA) F- and (CF3) RA- with RA representing a hydrogen atom or having any one of the meanings given below for RB and Rc, Y represents an OH, SH, NH 2, NHRB or NRBRC group, with RB and Rc different from a hydrogen atom and representing, independently of one another, a radical chosen from among: (i) alkyl chain, preferably C 1 -C 10, optionally interrupted by one or more oxygen or sulfur atom (s) or

 1. Compound of general formula 1 <Desc / Clms Page number 47>  in which - R 'and R "represent, independently of one another, a hydrocarbon radical having from 1 to 20 carbon atoms which may be a saturated or unsaturated, linear or branched acyclic aliphatic radical; a saturated, unsaturated cycloaliphatic radical; aromatic, monocyclic or polycyclic, whether or not incorporating one or more heteroatoms provided that when B represents a group SO2, n is zero, Rf represents a group CF3, Y represents a group NH2, then R 'and R "do not simultaneously represent a group unsubstituted phenyl ring; said cycloaliphatic radical being, if appropriate, carrying a

 function (s) carbonyl and optionally substituted with one or more halogen atoms or carboxyl groups, (ii) an alkenyl chain, preferably C2 to C10, optionally interrupted by one or more oxygen or sulfur atom (s) or carbonyl function (s) and optionally substituted by one or more halogen atom (s) or carboxyl group (s); (iii) an aryl group, preferably C6 to C12, optionally substituted with one or more halogen atoms or alkyl or alkenyl group (s); (iv) an arylalkyl group, preferably C7 to C15, optionally substituted with one or more halogen atom (s); (v) an arylalkenyl group, preferably C8 to C15, optionally substituted by one or more halogen atom (s); - symbolized a skeleton of general formula la or Ib. <Desc / Clms Page number 48>  saturated or unsaturated aliphatic radical, linear or branched with the alkyl chain which may be interrupted by one or more oxygen atoms and / or carbonyl function and optionally substituted at the end of the chain by an aromatic or non-aromatic cyclic radical; said radicals may optionally be substituted by one or more halogen atoms, preferably fluorine and / or one or more C1 to C6 alkyl radicals, preferably C1 to C4, or the two substituents R 'and R "are linked together so as to form a cycloaliphatic radical as defined above, - X represents a methylene group optionally substituted, - n is an integer ranging from zero to 3, and - Ar, and Ar2 symbolize, independently the one of the other two substituted or unsubstituted aromatic rings, condensed or not and optionally carrying one or more heteroatoms, preferably C6 to C12 and which can form ortho or ortho and peri-condensed systems between them, - x and y respectively locate the two links established between the skeleton symbolized by A and the amino groups and Y and its derivatives.  2. Compound according to claim 1, characterized in that B represents a group -SO2-.  3. Compound according to claim 1 or 2, characterized in that Y represents an NH 2 or NHRB group with RB as defined in claim 1.  4. Compound according to one of claims 1 to 3, characterized in that Rf represents (i) a halogen atom, preferably fluorine, (ii) a C1 to C10 alkyl radical or a C3 to C10 cycloalkyl monopoly - or per-halogen, <Desc / Clms Page number 49>  (iii) a phenyl radical substituted with at least one mono- or polyhalogenated C1-C4 alkyl radical, or (iv) a mono-, poly- or perhalogenated C6 aryl radical.  5. Compound according to one of claims 1 to 4, characterized in that Rf represents a radical CF3, C4F9, or a phenyl radical substituted with one or more halogen atoms, preferably fluorine, or with one or more alkyl groups. mono-, poly- or perfluorinated C, -C2.  6. Compound according to one of the preceding claims, characterized in that it meets the general formula b

 wherein: Rf, (x), (y) and Y are as defined in one of claims 1 to 5 and Ar1 and Ar2 together are a group derived from diphenyl-2, 2'diyl or a group dinaphthyl-2 , 2'-diyl.  7. Compound according to one of claims 1 to 5, characterized in that it meets the general formula has

<Desc / Clms Page number 50>  in which - Rf, X, n, (x), (y) and Y are as defined above in general formula 1, and - R 'and R "represent, independently of one another, a carbocyclic radical or heterocyclic, saturated, unsaturated, aromatic, monocyclic or polycyclic, provided that when n is zero, Rf is CF3, Y is NH2, then R 'and R "do not simultaneously represent an unsubstituted phenyl ring or R' and R "may be bonded so as to constitute with the carbon atoms which carry them a carbocyclic or heterocyclic radical having from 1 to 20 saturated, unsaturated, aromatic, monocyclic or polycyclic carbon atoms.  8. Compound according to one of claims 1 to 5 or 7, characterized in that n has the value 0.  9. Compound according to one of claims 1 to 5 or 7 and 8, characterized in that R 'and R "are bonded together so as to form with the carbon atoms which carry them a cyclohexyl radical.  10. Compound according to one of claims 1 to 5 and 7 to 9, characterized in that it is selected from - ammonium chloride (1S, 2S) -N-trifluoromethanesulfonyl-1,2cyclohexanediamine, - (1S, 2S) -N-trifluoromethanesulfonyl-1,2-cyclohexanediamine,

 - (1S, 2S) -N-trifluoromethanesulfonyl-1,2-cyclohexanediamine, - (1S, 2S) -NN- (Nonafluorobutanesulfonyl) -1,2-diphenylethylenediamine, - (1S, 2S) -N- (Nonafluorobutanesulfonyl) -1,2 cyclohexanediamine, - (1S, 2S) -N- (pentafluorophenylsulfonyl) -1,2 cyclohexanediamine, - (1S, 2S) -N- (pentafluorophenylsulfonyl) -1,2-diphenylethylenediamine, <Desc / Clms Page number 51>  (1S, 2S) -N- (3,5-bis (trifluoromethane) phenylsulfonyl) 1,2cyclohexanediamine, and - (1S, 2S) -N- (3,5-bis (trifluoromethane) phenylsulfonyl) 1,2-diphenylethylenediamine.  11. Compound according to one of the preceding claims, characterized in that it is in an optically active form.  12. Compound according to one of the preceding claims, characterized in that the two carbons of the general formula I, respectively involved at the level of the bonds symbolized by (x) and (y) constitute two centers of chirality of the same configuration.  13. Process for the preparation of a compound of general formula # as described in one of claims 1 to 12, characterized in that a compound of general formula II is reacted.

 with A and Y being as defined in claims 1 to 12 with a compound of general formula III Rf-BX '(III) with Rf and B being as defined in claims 1 to 5 and X' representing a halogen atom, preferably chlorine or fluorine or a group OS02Rf and in that said compound of general formula I. <Desc / Clms Page number 52>  14. Preparation process according to claim 13, characterized in that the reaction is carried out in the presence of a base.  15. Preparation process according to claim 13 or 14, characterized in that the compound of general formula II is reacted with the compound of general formula III in a molar ratio 11/111 less than or equal to 1.  16. Use of a compound of general formula # as defined in any one of claims 1 to 12 and in optically active form for the preparation of catalytic metal complex ligands useful for performing asymmetric syntheses in organic chemistry.  17. Use of a compound of general formula 1 as defined in one of claims 1 to 12 and in optically active form for the preparation of catalytic metal complex ligands useful for carrying out an enantioselective asymmetric hydrogenation of ketone derivatives.  18. Use of a compound of general formula # as defined in one of claims 1 to 12 in optically active form, for the preparation of catalytic metal complex ligands useful for performing enantioselective oxidation of hydroxyl functions.  19. A metal complex based on a transition metal and comprising as ligand of said metal at least one optically active form of a compound of general formula # as defined in one of claims 1 to 12. <Desc / Clms Page number 53>  20. Metal complex according to claim 19, characterized in that it corresponds to the general formula IV

 in which: - A, B, Rf and Y are as defined in one of claims 1 to 12, - the carbons bearing the bonds (x) and (y) have the same absolute configuration, - M is a metal of transition selected from rhodium, ruthenium, rhenium, iridium, cobalt, nickel, platinum and palladium, - Z represents a coordinating anionic ligand, and - L represents an unsaturated aliphatic ligand comprising at least one double bond or a carbocyclic or heterocyclic ligand preferably of 5 to 8 atoms and comprising at least one double bond, charged or not.  21. Complex according to claim 20, characterized in that - M represents ruthenium, rhodium or iridium, - Z represents a halogen atom, preferably chlorine or bromine, - L represents a C6 aromatic ligand at C12 or a cyclopentadienyl or cyclooctatriene unit optionally substituted by one or more C1-C4 alkyl groups.  22. Complex according to claim 19 or 21, characterized in that it corresponds to the general formula Va <Desc / Clms Page number 54>  in which: R 'and R "represent, independently of one another, a saturated, unsaturated, aromatic, monocyclic or polycyclic C1-C20 carbocyclic or heterocyclic radical as defined above, provided that when Rf represents a CF3 group , Y an NH 2 group, then R 'and R "do not simultaneously represent an unsubstituted phenyl ring or R' and R" are linked together so as to constitute with the carbon atoms which carry them a carbocyclic or heterocyclic radical of 4 to Saturated, unsaturated, aromatic, monocyclic or polycyclic atoms, and Rf represents (i) a halogen atom, preferably fluorine, (ii) a C1-C10 alkyl radical or a C3-C10 cycloalkyl radical; halogenated, (iii) a phenyl radical substituted by at least one polyhalogenated C1 to C4 radical, (iv) a mono-, poly- or perhalogenated phenyl radical and - Y, L and Z are as defined above.

 23. Complex according to one of claims 19 to 22, characterized in that it corresponds to the general formula IVb. <Desc / Clms Page number 55>  with L, Z and M as defined in claim 20 or 21.

 24. A complex according to claim 22 or 23, characterized in that - L represents an aromatic chosen from benzene, paramethylisopropylbenzene or hexamethylbenzene, - a chlorine atom or a bromine atom, and - M a ruthenium atom .  25. Complex according to one of claims 19 to 24, characterized in that it has as ligand at least one compound selected from (1S, 2S) -N-trifluoromethanesulfonyl-1,2-cyclohexanediamine, ( 1S, 2S) -N-trifluoromethanphenylsulfonyl-1,2-cyclohexanediamine, (1S, 2S) -NN- (Nonafluorobutanesulfonyl) -1,2-diphenylethylenediamine, (1S, 2S) -N- (Nonafluorobutanesulfonyl) -1 2 cyclohexanediamine, (1S, 2S) -N- (pentafluorophenylsulfonyl) -1,2 cyclohexanediamine, (1S, 2S) -N- (pentafluorophenylsulfonyl) -1,2-diphenylethylenediamine, (1S, 2S) -N (3,5-bis (trifluoromethane) phenylsulfonyl) 1,2-cyclohexanediamine, (1S, 2S) -N- (3,5-bis (trifluoromethane) phenylsulfonyl) 1,2-diphenylethylenediamine.  26. A process for preparing a complex according to one of claims 19 to 25, characterized in that it consists in reacting a compound of general formula I as defined in claims 1 to 12 and in an optically active form with the transition metal compound retained in a suitable organic solvent. <Desc / Clms Page number 56>  27. Use of a metal complex as defined in one of claims 19 to 25 to carry out the asymmetric reduction of a ketone derivative.  28. Use according to claim 27, characterized in that the compound bearing the ketonic function has the general formula V. In which - R 1 and R 2 represent, independently of each other: (i) an alkyl chain, preferably a C 1 to C 10 chain, optionally interrupted by one or more oxygen or sulfur atom (s) or a functional group ( s) carbonyl and optionally substituted with one or more halogen atoms or carboxyl groups, (ii) an alkenyl or alkynyl chain, preferably C2 to C10, optionally interrupted by one or more atom (s) or sulfur or a function (s) ) carbonyl and optionally substituted by one or more halogen atom (s) or carboxyl group (s); (iii) an aryl group, preferably C6 to C12, optionally substituted with one or more halogen atoms or alkyl or alkenyl group (s); (iv) an arylalkyl group, preferably C7 to C15, optionally substituted with one or more halogen atom (s); (v) an arylalkenyl group, preferably C8 to C15, optionally substituted by one or more halogen atom (s); - * indicates the possible presence R2 of an asymmetric center located in position a of the carbonyl function.  * R1-C-R2 V # <Desc / Clms Page number 57>  29. Process for preparing an optically active secondary alcohol of general formula VI OH

 - C 1 -R 2 (VI) 112 <VI> In which: R1 and R2 represent, independently of one another, (i) an alkyl chain, preferably a C1 to C10 chain, optionally interrupted by one or more atoms or sulfur or a function (s) carbonyl and optionally substituted by one or more halogen atoms or carboxyl groups, (ii) an alkenyl or alkynyl chain, preferably a C2 to C10 chain, optionally interrupted by one or more oxygen or sulfur atom (s) or function (s) carbonyl and optionally substituted by one or more halogen atom (s) or carboxyl group (s); (iii) an aryl group, preferably C6 to C12, optionally substituted with one or more halogen atoms or alkyl or alkenyl group (s); (iv) an arylalkyl group, preferably C 1 to C 15, optionally substituted with one or more halogen atoms; (v) an arylalkenyl group, preferably C8 to C15, optionally substituted by one or more halogen atom (s), and - * indicates the presence of a center of chirality at the carbon, characterized in that it implements the asymmetric reduction of a compound of general formula V R1-C-R2 (V) O <Desc / Clms Page number 58>  as defined in claim 28, in the presence of a metal complex whose transition metal has as ligand at least one optically active form of a compound of general formula 1 as defined in claims 1 to 12.  30. The method of claim 29, characterized in that the metal complex is as defined in claims 20 to 25.  31. The method of claim 29 or 30, characterized in that the complex is used in a proportion of 1 / 10,000 to 1/1 relative to the carbonyl compound of general formula V.  32. Method according to one of claims 29 to 31, characterized in that the reaction is carried out in the presence of a hydrogen donor.  33. Use of a metal complex as defined in one of claims 19 to 25 for carrying out the enantioselective catalytic oxidation of a chiral secondary alcohol in the form of a racemic mixture.