WO2011033022A2 - Osmium complexes usable as catalysts for the reduction of carbonyl compounds - Google Patents

Abstract

The invention relates to new osmium complexes of the type [OsX₂(P₂)(diamine)] (P = phosphorus atom of a diphosphine; X = anionic ligand), and to preparation thereof. Said systems, in the presence of bases, have proved to be highly efficient catalysts for the hydrogenation of aldehydes and the enantioselective hydrogenation of various types of ketones.

Description

OSMIUM COMPLEXES USABLE AS CATALYSTS FOR THE REDUCTION OF CARBONYL COMPOUNDS

Field of the invention

The invention relates to osmium(ll) complexes of the type [OsX₂(P2)(diamine)] (P = phosphorus atom of a diphosphine; X = anionic ligand), the preparation method thereof and their use as catalysts for the reduction of carbonyl compounds by hydrogen transfer or by hydrogenation. When the diamine ligand and/or the diphosphines used are optically active, several types of optically active secondary alcohols can be produced starting from prochiral ketone compounds. Hence, the invention also relates to a method for preparing chiral alcohols, these being important intermediates for the synthesis of pharmaceutical products and bioactive compounds.

State of the art

The reduction of carbonyl compounds, such as ketones and aldehydes, is a reaction of wide applicative interest which in recent years has led to intense research activity in this field.

Other than biocatalytic reduction methods and those based on the use of metal hydrides such as LiAIH₄, two further different hydrogenation methods have been developed: i) reduction with molecular hydrogen using catalytic systems based on transition metals; ii) catalytic reduction by hydrogen transfer, using donor systems such as formic acid or 2-propanol as the hydrogen source. Good results have been achieved with both methods, in particular by using systems based on ruthenium(ll) complexes containing various types of ligands. From an industrial viewpoint, both technologies present advantages and disadvantages although hydrogenation of carbonyl compounds with hydrogen gas is currently preferred due to the availability of highly active catalytic systems which operate at moderate temperatures, with high selectivity and limited production of by-products. For reduction with molecular hydrogen, catalytic systems based on various transition metals (Ir, Rh, Pd, Ni) have been used, but attention has been concentrated particularly on ruthenium derivatives. Compounds of the type [RuCI₂ (phosphine)₂(1 ,2-diamine)] and [RuCI₂(diphosphine)(1 ,2-diamine)] in a basic environment, are excellent catalysts for the selective hydrogenation, in homogeneous phase, of a lot of carbonyl compounds. In addition, with an appropriate combination of chiral diphosphines and diamines, the enantioselective hydrogenation of carbonyl compounds can be achieved with the production of optically active alcohols with high enantiomeric excesses. The presence of NH₂ groups (bifunctional mechanism) has a key role in determining the reactivity of Ru/diphosphine/diamine systems (T. Ohkuma et al. J. Am. Chem. Soc, 1995, 1 17, 10417; R. Noyori et al, Angew. Chem., Int. Ed. Engl., 2001 , 40, 40; R.H. Morris et al. Coord. Chem. Rev., 2004, 248, 2201 ). It is to be noted, however, that the [RuCI₂ (diphosphine)(1 ,2-diamine)] complexes have certain important limitations and are ineffective in the hydrogenation of bulky ketones.

Until recently, much less attention has been devoted to the use of osmium derivative-based systems as catalysts for the hydrogenation of carbonyl compounds (R. H. Morris, "Ruthenium and Osmium" in The Handbook of Homogeneous Hydrogenation, Vol. 1 -Eds. : J. G. de Vries, C. J. Elsevier - Wiley- VCH, Weinheim, 2007, p. 45; M. A. Esteruelas, A. M. Lopez, M.OIivan, Coord. Chem. Rev., 2007, 251 , 795). Of the hitherto used derivatives, the only example of the type [OsX₂(P₂)(diamine)] (P = phosphorus atom of a monodentate phosphine or a diphosphine; X = anionic ligand) is [OsHCI(NH₂CMe2CMe₂NH2)(PPh3)2] (S. E. Clapham, R. H. Morris, Organometallics, 2005, 24, 479) which has moderate catalytic activity in non-asymmetric hydrogenation.

Instead, complexes of the type [OsCI₂(P₂)(Pyme)] [P₂ = diphosphine; Pyme = 1 - (piridin-2-yl)methanamine)] (W. Baratta et al., Chem. Eur. J., 2008, 15, 726) and [OsCI(CNN)(P₂)] (HCCN =1 -(6-arylpiridin-2-yl)methanamine)] (W. Baratta et al., Angew. Chem. Int. Ed., 2008, 47, 4362) have been reported to be excellent catalysts for the reduction of ketones to alcohols with gaseous hydrogen. Recently, in WO 2009/055912 it is disclosed the cationic type complexes [MX_q(P)_m(N₂)(LB)_n]^r+[Y-]_r and [MX_q(P₂)(N₂)(LB)_n]^r+[Y-]_r (M = Fe, Ru, Os; X = anionic ligand; P = monophosphine; P₂ = diphosphine; N₂ = diamine; LB = Lewis base; Y = non-coordinating anion, m = 1 , 2; n = 0, 1 , 2; q = 0, 1 ; r = 1 , 2 and q+r = 2), usable as catalysts of unsaturated compounds both by hydrogenation and hydrogen transfer. Various derivatives of ruthenium and iron are described in this patent application, but although osmium is a foreseen metal, no specific mention is made of any osmium derivative, neither as a complex according to the aforementioned general formulas, nor as intermediates of the type OsX₂(P)m(N₂) and OsX₂(P₂)(N₂) for the synthesis of said complexes. It ensues that neither their formation nor their catalytic ability are extrapolatable to potential osmium-based complexes, from that described in the aforesaid patent application for ruthenium- and iron-based complexes, as it is known that the preparation methods for ruthenium or iron complexes often do not give equally satisfactory results in the synthesis of analogous osmium derivatives, their catalytic activity being also unpredictable.

Nonetheless, osmium-based catalytic systems can present undoubted advantages over ruthenium-based catalytic systems, since a higher thermal stability can be envisaged for complexes of osmium, being a 5d metal, than for analogous ruthenium (4d) complexes with the possibility, therefore, of having more robust and more productive catalysts.

The object of the present invention is therefore the preparation and characterization of new osmium(ll) complexes containing ligands selected from diphosphines and diamines usable as efficient catalysts in the asymmetric and non-asymmetric reduction of carbonyl compounds with gaseous hydrogen or by hydrogen transfer.

A further object of the present invention is to obtain osmium(ll) complexes which can be employed as catalysts generated in situ during the asymmetric and non- asymmetric reduction of carbonyl compounds.

Summary

To achieve the aforementioned objects the inventors have found that osmium/diphosphine/diamine systems, analogous to the ruthenium(ll) systems of Noyori et al., are efficient catalysts for the reduction of ketones and aldehydes to alcohols, with hydrogen gas or by hydrogen transfer in the presence of bases. By using an appropriate combination of chiral ligands, systems with both high catalytic activity and high enantioselectivity can be obtained, with results comparable to those of analogous ruthenium derivatives in terms of reactivity and productivity. Furthermore, compared to ruthenium analogues the osmium/diphosphine/diamine systems exhibit good catalytic activity in the hydrogenation of a broader range of substrates, including the enantioselective reduction of bulky ketones which are not hydrogenated with catalysts of the type [RuCI₂ (diphosphine)(1 ,2-diamine)].

The inventors have therefore identified, in the class of osmium(ll) complexes with diamine and diphosphine ligands, the system for obtaining catalysts with very high catalytic activity for reducing carbonyl compounds with gaseous hydrogen or by hydrogen transfer, with the possibility of also achieving enantioselective reductions by suitable combinations of chiral diphosphines and diamines. The catalysts are also obtainable by in situ synthesis processes during the reduction reaction of carbonyl compounds.

Therefore, object of the invention are the osmium(ll) complexes represented by the general formula (I)

wherein:

X, L, U can be:

X independently of each other a halogen, an alkoxide (OY) (Y = optionally substituted C-1 -C7 alkyl group) and a hydrogen atom;

L a diphosphine ligand selected from the groups:

a) a non-chiral bidentate phosphine selected from the group consisting of 1 ,4- bis(diphenylphosphino)butane (dppb), 1 ,1 '-bis(diphenylphosphino)ferrocene (dppf) and bis[2-(diphenylphosphino)phenyl]methanone (dpbp);

b) a chiral bidentate phosphine selected from the group consisting of (f?)-(6,6'- dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) [(fl)-MeObiphep], (fl)-(6,6'- dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-dimethylphenyl)phosphine] [(f?)-3,5- xylMeObiphep], (S)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) [(S)- MeObiphep], (f?)-(1 ,1 '-binaphthalene-2,2'-diyl)bis(diphenylphosphine) [(f?)-binap], (fl)-(1 ,1 '-binaphthalene-2,2'-diyl)bis[bis(3,5-dimethylmethyl)phosphine] [(fl)-3,5- xylbinap], (S)-(1 ,1 '-binaphthalene-2,2'-diyl)bis[bis(3,5-dimethylphenyl)phosphine] [(S)-3,5-xylbinap], (fl)-1 -{(S)-2-[bis(3,5-dimethyl-4- methoxyphenyl)phosphine]ferrocenyl} ethyldicyclohexylphosphine [{R,S)- josiphos*] and (2f?,4/^:?)-2,4-bis(diphenylphosphine)pentane [(R,R)-bdpp\;

U a diamine bidentate ligand represented by the general formula (II)

where R⁵, R⁶, R⁷ and R⁸ and the groups from R¹ to R⁴ can be equal to or different from each other and can be hydrogen atoms, linear or branched aliphatic groups, C1-C20 alkyls or C₂-C₂o alkenyls, C3-C20 cycloaliphatic groups and C₆-C₂2 aryl groups and where at least one among R⁵, R⁶, R⁷ and R⁸ is hydrogen, and the bridged group G can be a single bond or a -(CR'R")_X- chain with x equal to 1 or 2 wherein R' and R" can be equal to or different from each other and are H, saturated or unsaturated linear or branched aliphatic groups, cycloaliphatic groups and aryl groups having the aforementioned meanings for R¹ - R⁸.

The osmium(ll) complexes of the invention, in accordance with the configuration of the donor atoms bound to the metal, can be in the cis and/or trans isomeric configuration.

In a further aspect the object of the present invention is a method for preparing osmium(ll) complexes of general formula (I) which comprises the use of an osmium precursor which can be selected from a complex of formula [OsX₂(PAr₃)₃] (Ar = Ph, p-tolyl), [Os₂X₄(P(m-tolyl)₃)₅] and OsX₂{" ligand") where the "HgancT is an easily displaceable ligand such as benzene, p-cymene, cyclooctadiene and in which X has the meanings defined for the osmium(ll) complexes of the invention. The selected precursor is reacted with the ligands L and/or U, which are selected according to the osmium(ll) complexes to be prepared and are in excess of the reaction stoichiometry, in a hot organic solvent. In the case that the ligands X of the selected precursor should be partially or completely different from the ligands X of the osmium(ll) complex to be prepared, the reaction mixture is treated, either before or after the reaction step between the selected precursor and ligands L and/or U, with the ligands X selected for the osmium complex to be prepared. The precursors [OsX₂(PAr₃)₃] (Ar = Ph) and [Os₂X₄(P(m-tolyl)₃)₅], in which X = CI, are preferred and preferably to said precursors [OsX₂(PPh₃)₃] or [Os₂X₄(P(m-tolyl)₃)₅] after an initial reaction with the diphosphine ligand L selected from groups a) or b) in slight excess, the diamine U is added. For the preparation of osmium(ll) complexes of general formula (I) containing chiral bidentate phosphines, it was found to be convenient to start from the precursor with tri(m-tolyl)phosphine namely [Os₂CI₄(P(m-tolyl)₃)₅]. This intermediate is new and, hence, it is another aspect of the present invention.

Yet, further objects of the invention are the use of the osmium(ll) complexes of general formula (I) in which X, L and U have the aforedefined meanings, as catalysts for both symmetric and asymmetric reduction reactions of carbonyl compounds by hydrogenation or hydrogen transfer, and the symmetric and asymmetric reduction processes of carbonyl compounds catalyzed by the osmium(ll) complexes of the invention. For said use or processes, the osmium(ll) complexes can be used as such or obtained directly in situ during said reduction reaction. The reduction reactions are conducted in the presence of a base, preferably chosen from an alkali or alkaline earth metal hydroxide, an alkali metal alkoxide, a carbonate or hydrogen carbonate of an alkali metal. The most preferred bases are NaOH, NaOC₂H₅, NaO-/-C₃H₇, NaO-f-C₄H₉, Na₂C0₃, KOH, KO-/-C₃H₇, KO-f-C₄H₉, and in particular NaOC₂H₅.

The osmium(ll) complexes of the present invention can be used for the preparation of alcohols, possibly chiral, by the reduction of cyclic ketones, linear dialkyls, alkylaryl ketones and diarylketones of general formula R⁹C(=0)R¹⁰ where R⁹ and R¹⁰ represent, either independently or simultaneously, a possibly substituted saturated aliphatic [Ci_-20 alkyl] or a possibly substituted unsaturated aliphatic [C_2-20 alkenyl] group, or an aryl C₆-₂₂ group which can either have or not have alkyl substituent groups, substituent groups containing oxygen, halogen atoms, or in which the two R⁹ and R¹⁰ groups fused together form a ring. By using the same catalysts, aldehydes of the type R⁹C(=0)H can also be reduced to alcohols.

These and other aspects as well as the characteristics and advantages of the present invention will be better understood from the following detailed description and the preferred embodiments which are given for illustrative and non-limiting purposes. Detailed description of the invention

Definitions

The term "linear or branched aliphatic groups, Ci -C₂o alkyls or C₂-C₂o alkenyls, or C3-C20 cycloaliphatic groups" means: i) linear or branched alkyl radicals, optionally substituted, having from 1 to 20 carbon atoms and in particular alkyl radicals consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl and analogues thereof, these being the preferred for the purposes of the present invention; ii) linear or branched alkenyl radicals, optionally substituted, having from 2 to 20 carbon atoms and from one to three double bonds, in particular alkenyl radicals consisting of vinyl, allyl, 2-methylpropen-1 -yl, 1 -buten-1 -yl being the preferred for the purposes of the invention; iii) saturated monocyclic or polycyclic cycloalkyl radicals, optionally substituted, having from 3 to 20 carbon atoms, with radicals chosen from cyclopropyl, cyclobutyl, cyclopentyl, bicyclo[2.2.2]octanyl, bicyclo[3.1 .1 ]heptanyl being the preferred.

The term "C₆-C₂2 aryl" means a cyclic or polycyclic aromatic group, optionally substituted, having at least one aromatic ring; in particular, the groups selected from phenyl, tolyl, xylyl, naphthyl, indanyl, 1 ,2-dihydro-naphthyl, fluorenyl are the preferred for the purposes of the invention.

For clarity, the following table presents, as non-limiting examples of the invention, the chemical names, relative abbreviations and structures of the diphosphine ligands L (table 1 ) and the diamine ligands U (table 2) used for the preparation of some osmium(ll) complexes according to the invention.

Description

For the purposes of the invention the inventors have identified, in the osmium(ll) complexes of general formula (I) [OsX₂LL'] which from the previously indicated meanings are essentially of the type [OsX₂(diphosphine)(diamine)], a class of efficient catalysts for use in reduction reactions of carbonyl compounds in the presence of strong bases, and in particular with hydrogen gas at low pressure or with 2-propanol by hydrogen transfer. When the ligand U of diamine type and/or the diphosphines L are optically active, it has been shown that various kinds of optically active alcohols can be produced from carbonyl compounds such as prochiral ketones. It has also been shown that with the osmium(ll) complexes of the invention it is possible to achieve high efficient catalytic reduction of bulky ketones, such as those containing tertiary alkyl groups, these being generally difficult to reduce.

For the purposes of the present invention, in the osmium(ll) complexes of general formula (I) [OsX₂LL'] wherein:

- X is a ligand selected, independently of each other, from a halogen, an alkoxide (OY) (Y = optionally substituted C1 -C7 alkyl group), a hydrogen atom;

- L is a phosphine-type ligand selected from the previously indicated non- chiral and chiral bidentate phosphines of group a) and b) respectively; and

- L' is a diamine ligand of general formula (II) having the aforedefined meanings;

the preferred ligands are selected from:

- X a halogen, in particular chlorine and bromine, an alkoxide (OY) in which

Y is CH₂CF₃, a hydrogen;

- L the aforedefined non-chiral bidentate phosphines of group a) and chiral bidentate phosphines of group b); and

- U the non-chiral diamines ethylenediamine (en), 1 ,3-propanediamine (pn), 1 ,4-butanediamine (bn), 1 ,2-diaminocyclohexane (dach), N,N-dimethyl- ethylenediamine (Ν,Ν-dimen), and the chiral diamines (R,R)^ ,2- diphenylethylenediamine [(R,R)-dpen], {R,R}^ ,2-diaminocyclohexane [(fl,fl)-dach], (fl,fl)-1 ,3-diphenylpropanediamine [{R, fl)-dppn], (fl)-1 ,1 - dianisyl-2-isopropyl-1 ,2-ethylenediamine [(f?)-daipen].

For the osmium complexes of formula (I), the most preferred combinations between the different meanings of X, L, U for the purposes of the present invention are: X equal to a chlorine, a hydrogen, an alkoxide OY in which Y is CH₂CF₃;

L equal to a bidentate phosphine chosen from group a) or an optically active diphosphine selected from group b) in which the preferred ligands L of group a) are those previously indicated 1 ,1 '-bis(diphenylphosphino)ferrocene (dppf), bis[2- (diphenylphosphino)phenyl]methanone (dpbp), 1 ,4-bis(diphenylphosphino)butane (dppb), whereas the preferred ligands L of group b) are (f?)-(1 ,1 '-binaphthalene- 2,2'-diyl)bis(diphenylphosphine) [(fl)-binap], (fl)-(1 ,1 '-binaphthalene-2,2'- diyl)bis[bis(3,5-dimethylmethyl)phosphine] [(fl)-3,5-xylbinap], (S)-(1 ,1 '- binaphthalene-2,2'-diyl)bis[bis(3,5-dimethylphenyl)phosphine] [(S)-3,5-xylbinap], (f?)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) [(f?)-MeObiphep], (/=?)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-dimethylphenyl)phosphine] [(/=?)- 3,5-xylMeObiphep], (S)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) [(S)-MeObiphep], (fl)-1 -{(S)-2-[bis(3,5-dimethyl-4- methoxyphenyl)phosphine]ferrocenyl}ethyldicyclohexylphosphine [(A.S)- josiphos*], (2f?,4/^:?)-2,4-bis(diphenylphosphine)pentane [(R,R)-bdpp\; and

L' chosen from ethylenediamine (en), 1 ,3-propanediamine (pn), 1 ,4- butanediamine (bn), N,N-dimethyl-ethylenediamine (Ν,Ν-dimen), (~\ R,2R)-~\ ,2- diphenylethylenediamine [(R,R)-dpen], (1 R,2R)^ ,2-diaminocyclohexane [{R,R}- dach], (1 R,3R)A ,3-diphenylpropanediamine [(F^-dppn] and (/=?)-1 ,1 -dianisyl-2- isopropyl-1 ,2-ethylenediamine [(f?)-daipen).

The synthesis of the osmium(ll) complexes of the invention comprises at least the steps of selecting and reacting a suitable osmium precursor with ligands selected according to the osmium(ll) complex of the invention to be prepared. Said precursor can be an osmium complex selected from [OsX₂(PAr₃)₃] (Ar = Ph, p- tolyl) and [Os₂X₄(P(m-tolyl)₃)₅] in which X has the meanings previously defined for the osmium(ll) complex of the invention. Alternatively, the osmium precursor can be of the type OsX₂(" ligand") where X is a monoanion and the "Hgand' is an easily displaceable ligand such as benzene, p-cymene, cyclooctadiene. The diphosphine ligand L is added to the selected precursor in an organic solvent preferably selected from toluene and dichloromethane at a temperature comprised between 40 °C and 120°C; the diamine ligand U is then added to the same reaction mixture, both ligands being added in excess of the reaction stoichiometry. The ligand X can also be partially or completely replaced if, in the osmium(ll) complex to be prepared, it has the other envisaged meanings and is neither partially nor completely the ligand X of the selected precursor. For this substitution the reaction mixture can be further treated, either before or after the reaction between the osmium precursor and the chosen ligands L and/or U, with the desired ligands X for the osmium(ll) complex to be prepared so as to completely or partially replace said ligand X. Said treatments can be achieved by treating with a suitable reagent or by conducting the reaction in a H₂ atmosphere for hydride-type osmium(ll) complexes.

Optionally the method for preparing the osmium(ll) complexes of general formula (I) can comprise the additional steps of:

preparing and separating the precursor as intermediate of the osmium(ll) complexes of the invention; and

separating and purifying the osmium(ll) complexes from the reaction mixture, by means of methods known to an expert of the field and preferably with organic solvents selected from pentane, heptane and diethyl ether.

These steps are optional in that, for the aforesaid envisaged uses, the osmium(ll) complexes of the invention can also be prepared in situ, i.e. during the reduction reactions of carbonyl compounds.

By means of said preparation method, the osmium(ll) complexes of the invention can be obtained either in the cis, trans configuration or as a mixture of two diastereoisomers.

Preferably, the preparation comprises the following as starting products: the complex [Os₂CI₄(P(m-tolyl)₃)5] (1 ) or the compound [OsCI₂(PPh₃)₃] (Elliott, G. P., McAuley, N. M., Roper, W. R. Inorg. Synth., 1989, 26, 1849).

For complexes with chiral diphosphines, the starting precursor is preferably the compound [Os₂CI₄(P(m-tolyl)₃)5] (1 )

P = P(m-tolyl)₃ (1 )

as it enables the osmium(ll) complexes of the invention to be obtained in pure form. This complex precursor can be obtained with yields of 75% for a reaction at 120°C between [(NH₄)₂0sCI₆] and P(m-tolyl)₃ in a H₂0/iBuOH mixture (4/10 by volume).

Generally the process for preparing osmium complexes involves an initial reaction, under inert atmosphere and hot conditions (temperature comprised between 40 and 120°C), between the selected osmium precursor and the chosen diphosphine ligand, which is added in excess of the reaction stoichiometry, in an organic solvent, preferably toluene or dichloromethane. The diamine ligand is then added to the reaction mixture in slight excess. All the steps are carried out under inert gas atmosphere and the solvents used are dried and distilled prior to use.

The synthesis of the hydride derivatives starting from the precursors [OsCI₂(PPh₃)3] and [Os₂CI₄(P(m-tolyl)₃)₅], on the other hand, takes place in a hydrogen atmosphere which enables substitution of the ligand CI by H, hence enabling the osmium precursor used to be initially transformed in solution into [OsH₃CI(PAr₃)3] (Ar = phenyl, m-tolyl, p-tolyl), as described by Caulton (Inorg. Chem., 1999, 38, 4168).

Specific examples of isolated complexes used in catalysis are given below by way of non-limiting illustration of the present invention.

In particular hereinafter are described the osmium(ll) complexes of formula (I)

wherein L is a diphosphine which can be chiral or non-chiral and U is a diamine which can be chiral or not chiral, with the combinations given below:

a) where X = CI, L = dppf and L'= NH₂(CH₂)_nNH₂ [n = 2 (2), 3 (3), 4 (4)];

b) where L = dppf, L'= en and when X = CI, H (5) or OCH₂CF₃ (6);

c) where X = CI, U = en, Ν,Ν-dimen and when L = dpbp (7) or dppb (8)

The osmium(ll) complexes of the present invention can be used for the preparation of alcohols starting from the corresponding ketones, by hydrogenation or hydrogen transfer reactions. In the presence of the new osmium-based catalysts and for example of an alkali metal alkoxide, alcohols can be produced by reduction of R⁹C(=0)R¹⁰ cyclic ketones, linear dialkyls, alkylaryl ketones and diarylketones, where R⁹ and R¹⁰ represent a saturated or unsaturated aliphatic group or an aryl group, which can either have or not have substituent alkyl groups, oxygen-containing substituent groups, halogen atoms, or a heterocyclic group. For said reduction catalysis processes, the reaction conditions are:

i) use of a solvent, with alcoholic solvents, such as methanol, ethanol, 2- propanol, butanol, benzyl alcohol and the like, being particularly preferred, with ethanol being the most preferred for hydrogenation and 2-propanol the most preferred for hydrogen transfer;

ii) a S/C ratio of the carbonyl compound (S) to the osmium(ll) catalyst (C) of the invention, which may vary between values ranging from 100 to 200000, but preferably between 1000 and 50000;

iii) the presence of bases, such as NaOH, KOH, NaOEt, NaOCH(CH₃)₂, KOCH(CH₃)₂ and the like, in a ratio of base to osmium(ll) complex which can vary between 1 and 2000, but preferably between 10 and 500.

In the case of catalytic reduction by hydrogenation, although a pressure of one hydrogen atmosphere is sufficient, this may vary between 1 and 100 atm, and preferably between 5 and 20 atm. The reaction temperature may vary between 20 and 100°C, being preferably between 30 and 70 °C. The time necessary to complete the reaction varies from a few minutes to 48 hours depending on the temperature, the nature of the substrate and the hydrogen pressure.

In the case of catalytic reduction by hydrogen transfer, the reaction is conducted in 2-propanol at 60 °C or at the reflux temperature of the solvent.

The invention is illustrated by examples of the synthesis of the osmium(ll) complexes of the invention and by catalytic reduction tests carried out therewith on different carbonyl compounds. The synthesis and the characterization of the osmium(ll) complexes are detailed hereinafter. The compounds were characterized by elemental analysis, mass analysis and the ¹H NMR, ¹³C{¹ H} NMR and ³¹ P{¹H} NMR nuclear magnetic resonance measurements.

A. Synthesis of osmium(ll) complexes

The synthesis of the complexes (2-5), (7), (9), (10), (25) of the invention entails the use of compound [OsCI₂(PPh₃)₃] as the starting product, which can be prepared by reacting [(NH₄)₂0sCI₆] with triphenylphosphine (Elliott, G. P. et al. ref. cit), while the derivatives (8), (11-24, 26) were prepared starting from the complex [Os₂CI₄(P(m-tolyl)₃)₅] (1 ) obtained by reacting [(NH₄)₂0sCI₆] with P(m-tolyl)₃ in a H₂0/tBuOH mixture at reflux temperature. All the procedures were carried out under inert gas atmosphere, and the solvents were dried and distilled before use. The syntheses and characterizations of the osmium(ll) complexes (1-26) are detailed hereinafter. The complexes were characterized by elemental analysis, mass analysis and the ¹ H NMR, ¹³C{¹H} NMR and ³¹ P{¹H} NMR nuclear magnetic resonance measurements.

Example 1 . Synthesis of [Os₂CI₄(P(m-tolyl)₃)5] (1 )

[(NH₄)₂0sCI₆] (1 .50 g, 3.42 mmol) and P(m-tolyl)₃ (4.20 g, 13.8 mmol) were added to a solution of ie/t-butanol (130 mL) and water (55 mL). The suspension was heated to 120°C for 24 h. The red precipitate was washed with water (2x15 mL), heptane (3x15 mL), pentane (1 x15 mL) and dried under reduced pressure. Yield: 2.61 g (75 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 9.72 (m, 1 H; aromatic proton), 8.82 (broad s, 1 H; aromatic proton), 8.24 (t, J(H,H) = 5.4 Hz, 1 H; aromatic proton), 8.10-5.95 (m, 57H; aromatic protons), 2.26 (s, 3H; Me), 2.15-1 .81 (m, 33H; Me), 1 .71 (s, 3H; Me), 1 .67 (s, 3H; Me), 1 .26 ppm (s, 3H; Me); ¹³C{¹ H} NMR (50.3 MHz, C₆D₅CD₃, 20°C): δ = 141 .9-124.2 (m; aromatic carbon atoms), 22.5- 20.9 ppm (m; Me); ³¹ P{¹ H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = -13.4 (t, ²J(P,P) = 1 1 .5 Hz), -15.4 (d, ²J(P,P) = 17.2 Hz), -16.8 (d, ²J(P,P) = 17.2 Hz), -18.1 (broad t ²J(P,P) = 1 1 .5 Hz), -19.6 ppm (t, ²J(P,P) = 1 1 .5 Hz;); elemental analysis (%) calculated for Cio₅Hio5CI₄OsP₅: C 61 .70, H 5.18; found: C 61 .90, H 5.23; ESI-MS (MeOH): m/z = 2042.8 [100, (M-CI+MeOH)⁺], 1 139.3 [26, (OsCI(P(m-tolyl)₃)₃ ⁺]. Example 2. Synthesis of irans-[OsCI₂(dppf)(en)] (2)

[OsCI₂(PPh₃)₃] (150 mg, 0.143 mmol) and dppf (87 mg, 0.157 mmol) were dissolved in dichloromethane (3.0 mL) and the solution was refluxed for 3 h. The ethylenediamine ligand (9.6 μί, 0.143 mmol) was added at room temperature and the solution was heated to 40°C for 1 h. The solution was concentrated (1 .5 mL) and on addition of diethyl ether (4 mL) the formation of a yellow precipitate was observed. The solid was filtered off, washed with diethyl ether (2x3 mL) and was dried under reduced pressure. Yield: 108 mg (86 %). ¹ H NMR (200.1 MHz, CD₂CI₂, 20°C): δ = 7.79-7.28 (m, 20H; Ph), 4.58 (m, 4H; C₅H₄), 4.16 (t, J = 1 .7 Hz, 4H; C₅H₄ ), 3.12 (broad s, 4H; CH₂), 2.65 ppm (broad s, 4H; NH₂); ¹³C{¹H} NMR (50.3 MHz, CD₂CI₂, 20°C): δ = 140.7 (dd, J(C,P) = 53.1 , 8.6 Hz; ipso Ph), 134.5 (t, J(C,P) = 4.9 Hz; Ph), 129.0 (t, J(C,P) = 0.9 Hz; Ph), 127.4 (pseudo t, J(C,P) = 4.5 Hz; Ph), 89.9 (d, J(C,P) = 55.5 Hz; ipso C₅H₄), 76.3 (t, J(C,P) = 3.8 Hz; C₅H₄), 70.2 (t, J(C,P) = 2.9 Hz; C₅H₄), 44.0 ppm (s; CH₂); ³¹ P{¹H} NMR (81 .0 MHz, CD₂CI₂, 20 °C): δ = - 10.1 ppm (s); elemental analysis (%) calculated for C₃₆H₃₆CI₂FeN₂OsP₂: C 49.38, H 4.14, N 3.20; found: C 48.86, H 4.10, N 3.18. Example 3. Synthesis of irans-[OsCI₂(dppf)(pn)] (3)

[OsCI₂(PPh₃)₃] (150 mg, 0.143 mmol) and dppf (87 mg, 0.157 mmol) were dissolved in dichloromethane (3.0 mL) and the solution was refluxed for 3 h. The ligand 1 ,3-propanediamine (12 μί, 0.144 mmol) was added at room temperature and the solution was heated to 40°C for 1 h. The solution was concentrated (1 .5 mL) and on addition of diethyl ether (4 mL) the precipitation of a yellow solid was observed. The precipitate was filtered off, washed with diethyl ether (2x3 mL) and was dried under reduced pressure. Yield: 1 1 1 mg (87 %). ¹H NMR (200.1 MHz, CD₂CI₂, 20°C): δ = 7.75-7.28 (m, 20H; Ph), 4.57 (m, 4H; C₅H₄), 4.15 (t, J = 1 .8 Hz, 4H; C₅H₄), 3.32 (broad s, 4H; NCH₂), 2.81 (broad s, 4H; NH₂), 1 .68 ppm (broad m, 2H; CH₂); ¹³C{¹ H} NMR (50.3 MHz, CD₂CI₂, 20°C): δ = 139.0 (dd, J(C,P) = 51 .8, 8.6 Hz; ipso Ph), 135.0 (t, J(C,P) = 4.8 Hz; Ph), 129.2 (t, J(C,P) = 0.9 Hz; Ph), 127.4 (pseudo t, J(C,P) = 4.4 Hz; Ph), 88.6 (dd, J(C,P) = 61 .8, 5.5 Hz; ipso C₅H₄), 76.2 (t, J(C,P) = 3.8 Hz; C₅H₄), 70.4 (t, J(C,P) = 2.9 Hz; C₅H₄), 38.6 (s; NCH₂), 29.1 ppm (s; CH₂); ³¹ P{¹ H} NMR (81 .0 MHz, CD₂CI₂, 20 °C): δ = - 10.5 ppm (s); elemental analysis (%) calculated for C₃7H₃₈CI₂FeN₂OsP₂: C 49.95, H 4.31 , N 3.15; found: C 49.99, H 4.47, N 2.98.

Example 4. Synthesis of irans-[OsCI₂(dppf)(bn)] (4)

[OsCI₂(PPh₃)₃] (150 mg, 0.143 mmol) and dppf (87 mg, 0.157 mmol) were dissolved in dichloromethane (3.0 mL) and the solution was refluxed for 3 h. 1 ,4- butanediamine (14 μί, 0.143 mmol) was added at room temperature to the solution and heated to 40°C for 1 h. The solution was concentrated (1 .5 mL) and on addition of pentane (4 mL) the precipitation of a yellow solid was observed. The solid was filtered off, washed with pentane (2x3 mL) and was dried under reduced pressure. Yield: 106 mg (82 %). ¹ H NMR (200.1 MHz, CD₂CI₂, 20°C): δ = 7.73- 7.28 (m, 20H; Ph), 4.57 (m, 4H; C₅H₄), 4.15 (s, 4H; C₅H₄ ), 3.19 (broad s, 4H; NCH₂), 2.77 (broad s, 4H; NH₂), 1 .59 ppm (broad s, 4H; CH₂); ¹³C{¹H} NMR (50.3 MHz, CD₂CI₂, 20 °C): δ = 139.1 (dd, J(C,P) = 53.0, 9.6 Hz; ipso Ph), 135.0 (t, J(C,P) = 4.8 Hz; Ph), 129.3 (t, J(C,P) = 0.9 Hz; Ph), 127.4 (pseudo t, J(C,P) = 4.5 Hz; Ph), 88.1 (dd, J(C,P) = 62.5, 5.9 Hz; ipso C₅H₄), 76.2 (t, J(C,P) = 3.9 Hz; C₅H₄), 70.5 (t, J(C,P) = 2.9 Hz; C₅H₄), 41 .6 (s; NCH₂), 28.9 ppm (s; CH₂); ³¹ P{¹H} NMR (81 .0 MHz, CD₂CI₂, 20°C): δ = - 1 1 .0 ppm (s); elemental analysis (%) calculated for C₃₈H₄oCI₂FeN₂OsP₂: C 50.51 , H 4.46, N 3.10; found: C 50.94, H 4.42, N 3.00.

Example 5. Synthesis of irans-[OsHCI(dppf)(en)] (5)

[OsCI₂(PPh₃)₃] (100 mg, 0.095 mmol) was dissolved in toluene (20 mL) and NEt₃ (20 μΙ_, 0.143 mmol) was added under H₂ (1 atm) to form [OsH₃CI(PPh₃)₃], as described by Caulton (G. Ferrando, K. G. Caulton, Inorg. Chem., 1999, 38, 4168). The phosphine dppf (63 mg, 0.1 14 mmol) was added and the solution was heated to 60°C for 2 h under H₂ atmosphere. Ethylenediamine (7.6 μί, 0.1 14 mmol) was added at room temperature and the solution was heated to 60 °C for 3 h under H₂. The resulting solution was concentrated (0.5 mL) and on addition of diethyl ether (4 mL) the precipitation of NEt₄CI was observed, which was filtered off and washed with diethyl ether (2x3 mL) and toluene (1 x2 mL). The filtrate was concentrated (1 mL) and on addition of heptane (4 mL) the formation of a solid was observed, which was filtered off, washed with heptane (3x5 mL) at 60 °C and dried under reduced pressure. Yield: 50 mg (63 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.43-6.76 (m, 20H; Ph), 4.76 (s, 2H; C₅H₄), 4.35 (s, 2H; C₅H₄), 4.07 (s, 2H; C₅H₄), 3.85 (s, 2H; C₅H₄), 2.60 (broad s, 2H; CH₂), 2.25 (broad s, 2H; CH₂), 1 .93 (broad s, 2H; NH₂), 1 .41 (broad s, 2H; NH₂), -20.8 ppm (t, J(P,H) = 17.0 Hz, 1 H; OsH); ¹³C{¹H} NMR (50.3 MHz, C₆D₂₆, 20°C): δ = 136.7-125.6 (m; aromatic carbon atoms), 71 .0 (s; C₅H₄), 70.3 (s; C₅H₄), 45.3 (s; CH₂); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20 °C): δ = 14.5 ppm (s); elemental analysis (%) calculated for C₃₆H₃₇CIFeN₂OsP₂: C 51 .41 , H 4.43, N 3.33; found: C 51 .68, H 4.51 , N 3.39.

Example 6. Synthesis of ira/7s-[Os(OCH₂CF₃)₂(dppf)(en)] (6)

Sodium ethoxide, obtained by removing the solvent from a 0.25 M solution of NaOEt in ethanol (1 mL, 0.25 mmol), was reacted with frans-[OsCI₂(dppf)(en)] (2) (100 mg, 0.1 14 mmol) and 2,2,2-trifluoroethanol (42 μΙ_, 0.576 mmol) in toluene (4 mL) at 1 10°C for 1 h. The resulting dark orange solution was cooled to -20 °C for 4 h to allow NaCI to precipitate, and was then filtered through celite. The filtrate was concentrated (1 mL) and on addition of pentane (4 mL) the formation of a yellow- orange precipitate was observed, which was filtered off, washed with pentane (2x5ml_) and dried overnight under reduced pressure. Yield: 91 mg (80 %). ¹ H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.26 (pseudo t, J(H,H) = 8.6 Hz, 3H; Ph ), 7.71 (broad s, 1 H; Ph), 7.31 -6.98 (m, 15H; Ph), 6.74 (s, 1 H; Ph), 4.69 (s, 1 H; C₅H₄), 4.57 (m, 1 H; OCH₂), 4.35-4.25 (s, 2H; C₅H₄ and CH₂), 3.81 -3.47 (s, 10H; C₅H₄, CH₂ and NH₂), 3.24 (t, J(H,H) = 10.1 Hz, 1 H; CH₂), 2.93-1 .51 (broad m, 5H; CH₂ and NH₂), ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 142.7 (d, J(C,P) = 38.7 Hz; ipso Ph), 141 .8 (d, J(C,P) = 27.3 Hz; ipso Ph), 140.9 (d, J(C,P) = 21 .8 Hz; ipso Ph), 139.6 (d, J(C,P) = 45.5 Hz; ipso Ph), 135.3-127.0 (m; aromatic carbon atoms and CF₃), 85.2 (d, J(C,P) = 53.5 Hz; ipso C₅H₄), 82.1 (d, J(C,P) = 52.9 Hz; ipso C₅H₄), 76.6 (m; C₅H₄), 75.2 (s; C₅H₄), 74.8 (d, J(C,P) = 8.2 Hz; C₅H₄), 73.8 (d, J(C,P) = 9.0 Hz; C₅H₄), 71 .6 (d, J(C,P) = 5.5 Hz; C₅H₄), 71 .1 (d, J(C,P) = 4.9 Hz; C₅H₄), 70.3 (q, J(C,F) = 29.5 Hz; CH₂CF₃), 69.8 (d, J(C,P) = 5.5 Hz; C₅H₄), 64.8 (q, J(C,F) = 29.3 Hz; CH₂CF₃), 50.9 (d, J(C,P) = 2.7 Hz; CH₂NH₂), 41 .0 ppm (d, J(C,P) = 1 .9 Hz; CH₂NH₂); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = 1 .6 (d, ²J(P,P) = 19.8 Hz), -20.6 ppm (d, ²J(P,P) = 19.8 Hz); ¹⁹F{¹H} NMR (188.3 MHz, C₆D₆, 20°C): δ = -34.5 (s), -36.1 (s) ppm; elemental analysis (%) calculated for C₄₀H₄₀F₆FeN₂O₂OsP₂: C 47.91 , H 4.02, N 2.79; found: C 48.01 , H 4.10, N 2.74. Example 7. Synthesis of irans-[OsCI₂(dpbp)(en)] (7)

[OsCI₂(PPh₃)₃] (50 mg, 0.048 mmol) and dpbp (32 mg, 0.058 mmol) were dissolved in toluene (2.0 mL). The solution was stirred at 1 10°C for 2 h. Ethylenediamine (26 mg, 0.124 mmol) was added at room temperature, followed by stirring of the reaction mixture for 3 h at 1 10°C. The resulting suspension was concentrated (0.5 mL) and pentane (4 mL) was added thereto. The yellow precipitate obtained was filtered off, washed with pentane (2x3 mL) and was dried overnight under reduced pressure. Yield: 35 mg (84 %). ¹H NMR (200.1 MHz, CD₂CI₂, 20°C): δ = 7.99 (d, J(H,H) = 6.6 Hz, 2H; aromatic protons), 7.57 (t, J(H,H) = 7.4 Hz, 2H; aromatic protons), 7.38-6.88 (m, 24H; aromatic protons), 3.68 (broad s, 2H; CH₂), 3.54 (broad s, 2H; CH₂), 2.95 ppm (broad s, 4H; NH₂); ¹³C{¹H} NMR (50.3 MHz, CD₂CI₂, 20°C): δ = 151 .5 (d, J(C,P) = 25.8 Hz; CCO), 143.2- 128.3 (m; aromatic carbon atoms), 46.0 ppm (s; CH₂); ³¹ P{¹H} NMR (81 .0 MHz, CD₂CI₂, 20°C): δ = - 1 .6 ppm (s); elemental analysis (%) calculated for C₃₉H₃₆CI₂N₂OOsP₂: C 53.73, H 4.16, N 3.21 ; found: C 53.83, H 4.20, N 3.18. Example 8. Synthesis of frans-[OsCI₂(dppb)(N,N-dmen)] (8)

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and dppb (46 mg, 0.108 mmol) were dissolved in toluene (1 mL) and the solution was refluxed at 120°C for 2 h. The ligand N,N-dimethylethyenediamine (1 1 μί, 0.098 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 mL) was added to the product and again evaporated. Heptane (5 mL) was added to the obtained product and the formation of a yellow precipitate was observed. The obtained solid was filtered off, washed with heptane (2x3 mL) and dried under reduced pressure. Yield: 60 mg (79 %). ¹ H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.05 (broad t, J(H,H) = 7.6 Hz, 4H; aromatic protons), 7.68 (broad t, J(H,H) = 6.7 Hz, 4H; aromatic protons), 7.25-6.92 (m, 12H; aromatic protons), 3.28 (m, 2H; PCH₂), 2.99 (broad t, J(H,H) = 9.7 Hz, 2H; PCH₂), 2.79 (s, 2H; NCH₂), 2.35 (s, 6H; CH₃), 1 .95-1 .76 (m, 4H; NCH₂, NH₂), 1 .45-1 .30 ppm (m, 4H, CH₂); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 141 .3 (d, J(C,P) = 37.5 Hz; aromatic ipso carbon atom), 139.5 (d, J(C,P) = 46.7 Hz; aromatic ipso carbon atom), 134.5 (d, J(C,P) = 8.2 Hz; aromatic carbon atom), 133.9 (d, J(C,P) = 7.5 Hz; aromatic carbon atom), 128.8-127.4 (m; aromatic carbon atoms), 65.1 (s; CH₂NMe₂), 49.8 (s; CH₃), 41 .9 (t, J(C,P) = 1 .5 Hz; CH₂NH₂), 30.7 (d, J(C,P) = 31 .2 Hz; PCH₂), 24.5 (d, J(C,P) = 32.5 Hz; PCH₂), 24.2 (s; PCH₂CH₂), 20.4 ppm (d, J(C,P) = 5.8 Hz; PCH₂CH₂); ³¹ P{¹ H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 17.2 (d, J(P,P) = 13.1 Hz), -18.5 ppm (d, J(P,P) = 13.1 Hz); elemental analysis (%) calculated for C₃₂H₄₀CI₂N₂OsP₂: C 49.55, H 5.20, N 3.61 ; found: C 50.03, H 5.12, N 3.42.

Example 9. Synthesis of frans-tOsCl^dppfX^F -dpen)] (9)

[OsCI₂(PPh₃)₃] (150 mg, 0.143 mmol) and dppf (87 mg, 0.157 mmol) were dissolved in toluene (3.0 mL) and the solution was heated to 70 °C for 2 h. The ligand (F^-dpen (33 mg, 0.157 mmol) was added at room temperature and the solution was heated to 100°C for 1 h. The solution was concentrated (1 .5 mL) and on addition of pentane (4 mL) the precipitation of a yellow solid was observed. The precipitate was filtered off, washed with pentane (2x3 mL) and was dried under reduced pressure. Yield: 109 mg (74 %). NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.20 (m, 4H; aromatic protons), 8.10 (m, 4H; aromatic protons), 7.42-6.68 (m, 22H; aromatic protons); 5.06 (m 2H; C₅H₄), 4.95 (m, 2H; C₅H₄ ), 4.49 (br m, 2H; NCH), 4.17 (br t, J(H,H) = 7.8 Hz, 2H; NH₂), 3.96 (m, 4H; C₅H₄ ), 3.69 ppm (br d, J(H,H) = 7.8 Hz, 2H; NH₂); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 141 .6 (pseudo t, J(C,P) = 8.6 Hz; ipso Ph), 140.5 (pseudo t, J(C,P) = 9.1 Hz; ipso Ph), 139.3 (t, J(C,P) = 1 .0 Hz; ipso Ph), 135.1 -127.0 (m; aromatic carbon atoms), 90.7 (dd, J(C,P) = 61 .1 , 5.8 Hz; ipso C₅H₄), 76.8 (t, J(C,P) = 3.9 Hz; C₅H₄), 76.6 (t, J(C,P) = 3.7 Hz; C₅H₄), 70.3 (t, J(C,P) = 2.8 Hz; C₅H₄), 70.2 (t, J(C,P) = 2.8 Hz; C₅H₄), 64.0 ppm (s; NCH); ³¹ P{¹ H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 8.7 ppm (s); elemental analysis (%) calculated for C₄₈H₄₄CI₂FeN₂OsP₂: C 56.09, H 4.32, N 2.73; found: C 56.12, H 4.24, N 2.60.

Example 10. Synthesis of irans-[OsCI₂(dpbp)((/^:?,/^:?)-dpen)] (10)

[OsCI₂(PPh₃)₃] (100 mg, 0.095 mmol) and dpbp (63 mg, 0.1 14 mmol) were dissolved in toluene (2.0 mL) and the solution was stirred at 1 10°C for 2 h. The ligand (F^-dpen (26 mg, 0.124 mmol) was added at room temperature and the solution was stirred at 1 10°C for 3 h. After concentrating the solution (0.5 mL), on addition of pentane (4 mL) the formation of a precipitate was observed, which was filtered off, washed with pentane (2x3 mL) and dried overnight under reduced pressure. Yield: 78 mg (80 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.44 (d, J(H,H) = 7.0 Hz, 1 H; aromatic proton), 8.36 (d, J(H,H) = 7.5 Hz, 1 H; aromatic proton), 7.89 (pseudo t, J(H,H) = 9.0 Hz, 2H; aromatic protons), 7.70-6.26 (m, 34H; aromatic protons), 5.60 (broad s, 1 H; NH), 5.03 (broad t, J(H,H) = 12.4 Hz, 1 H; NCH), 3.75-3.45 (m, 3H; NH₂) 3.12 ppm (broad t, J(H,H) = 12.4 Hz, 1 H; NCH); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 153.7 (d, J(C,P) = 25.7 Hz; CCO), 152.5 (d, J(C,P) = 27.5 Hz; CCO), 140.0-128.0 (m; aromatic carbon atoms), 66.8 (s; CH), 63.3 ppm (s; CH); ³¹ P{¹ H} NMR (81 .0 MHz, C₆D₆, 20°C): δ 2.2 (d, ²J(P,P) = 5.0 Hz), -2.5 ppm (d, ²J(P,P) = 5.0 Hz); elemental analysis (%) calculated for C₅i H₄₄CI₂N₂OOsP₂: C 59.82, H 4.33, N 2.74; found: C 59.74, H 4.40, N 2.64.

Example 1 1 . Synthesis of ira/7s-[OsCI₂((S)-MeObiphep)(en)] (11 )

[Os₂CI₄(P(m-tolyl)₃)₅] (100 mg, 0.049 mmol) and (S)-MeObiphep (34 mg, 0.059 mmol) were dissolved in toluene (1 mL) and the solution was heated to 120°C for 3 h. After adding ethylenediamine (2.4 μί, 0.036 mmol) the solution was heated to 120°C for 1 h. The resulting solution was concentrated (0.5 mL) and heptane (5 mL) was added thereto. The yellow precipitate was filtered off, washed with heptane (3x5 mL) at 60 °C and dried under reduced pressure. Yield: 60 mg (65 %). NMR (200.1 MHz, C₆D₆, 20 °C): δ = 8.25-8.12 (m, 8H; aromatic protons), 7.65-6.76 (m, 16H; aromatic protons), 6.00 (d, J(H,H) = 8.0 Hz, 2H; aromatic protons), 3.17 (broad d, 2H; CH₂), 2.95 (s, 6H; OMe), 2.71 (m, 2H; CH₂), 1 .91 ppm (broad s, 4H; NH₂); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 140.7- 109.9 (m; aromatic carbon atoms), 54.1 ppm (s; OMe), 43.2 ppm (s; NCH₂); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20 °C): δ = - 12.4 ppm (s); elemental analysis (%) calculated for C₄₀H₄₀CI₂N₂O₂OsP₂: found: C 53.16, H 4.46, N 3.10; C 53.35, H 4.52, N 3.06. Example 12. Synthesis of irans-[OsCI₂((/=?)-MeObiphep)((/^:?,/^:?)-dpen)] (12)

[Os₂CI₄(P(m-tolyl)₃)₅] (100 mg, 0.049 mmol) and (f?)-MeObiphep (63 mg, 0.108 mmol) were dissolved in toluene (1 mL) and the solution was refluxed at 120°C for 4 h. The ligand (F^-dpen (23 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solution was concentrated (0.5 mL) and on addition of heptane (5 mL) the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 mL) and dried under reduced pressure. Yield: 66 mg (64 %). NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.33 (m, 4H; aromatic protons), 8.21 (t, J(H,H) = 7.2 Hz, 4H; aromatic protons), 7.80-6.64 (m, 26H; aromatic protons), 6.04 (t, J(H,H) = 8.1 Hz, 2H; aromatic protons), 4.54 (broad m, 2H; CH), 4.17 (broad s, 4H; NH₂), 2.94 (s, 6H; OMe); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 158.1 (t, J(C,P) = 5.3 Hz, COMe), 142.0- 1 10.1 (m; aromatic carbon atoms), 63.9 (s; NCH), 54.4 ppm (s; OMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 1 1 .6 ppm (s); elemental analysis (%) calculated for C₅2H₄₈CI₂N₂O₂OsP₂: C 59.14, H 4.58, N 2.65; found: C 59.60, H 4.58, N 2.49.

Example 13. Synthesis of irans-[OsCI₂((S)-MeObiphep)((/^:?,/^:?)-dpen)] (13)

The irans-[OsCI₂((S)-MeObiphep)((/^:?,/^:?)-dpen)] complex was prepared by following the procedure used for the synthesis of the trans-[OsC\₂{{R)- MeObiphep)((f?,/^:?)-dpen)] (12) complex, but substituting the ligand (S)-MeObiphep for the ligand (fl)-MeObiphep. Yield: 64 mg (62 %). NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.30 (m, 8H; aromatic protons), 7.80-6.64 (m, 26H; aromatic protons), 6.02 (t, J(H,H) = 9.2 Hz, 2H; aromatic protons), 4.81 (broad m, 2H; NH₂), 4.68 (broad m, 2H; NCH), 3.75 (broad d, J(H,H) = 10.1 Hz, 2H; NH₂), 2.95 ppm (s, 6H; OMe); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 158.0 (t, J(C,P) = 5.4 Hz, COMe), 139.6- 1 10.1 (m; aromatic carbon atoms), 64.1 (s; NCH), 54.1 ppm (s; OMe); ³¹ P{¹ H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 1 1 .8 ppm (s); elemental analysis (%) calculated for C₅₂H₄₈Cl₂N₂O₂OsP₂: C 59.14, H 4.58, N 2.65; found: C 59.53, H 4.73, N 2.37.

Example 14. Synthesis of irans-[OsCI₂((/^:?)-xylMeObiphep)((/^:?,/^:?)-dpen)] (14)

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and (f?)-xylMeObiphep (75 mg, 0.108 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (R,R)-dpen (23 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 ml_) was added to the product and again evaporated. Heptane (5 ml_) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. Yield: 62 mg (54 %). NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.04 (broad t, J(H,H) = 8.1 Hz, 8H; aromatic protons), 7.43-6.68 (m, 16H; aromatic protons), 6.52 (s, 2H; aromatic protons), 6.01 (d, J(H,H) = 7.8 Hz, 2H; aromatic protons), 4.54 (broad s, 2H; CH), 4.08 (broad s, 4H; NH₂), 3.03 (s, 6H; OMe), 2.1 1 (s, 12H; CMe), 2.08 ppm (s, 12H; CMe); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): 158.1 (pseudo t, J(C,P) = 5.3 Hz, COMe), 143.3- 109.9 (m; aromatic carbon atoms), 64.1 (s; NCH), 54.3 (s; OMe), 21 .6 (s; CMe), 21 .5 ppm (s; CMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 12.9 ppm (s); elemental analysis (%) calculated for C₆oH6 Cl2N₂O2OsP2: C 61 .69, H 5.52, N 2.40; found: C 61 .35, H 5.64, N 2.40.

Example 15. Synthesis of irans-[OsCI₂((^-binap)((fl,^-dpen)] (15)

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and (fl)-binap (67 mg, 0.108 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (R,R)-dpen (23 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 ml_) was added to the product and again evaporated. Heptane (5 ml_) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. Yield: 63 mg (59 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.66 (t, J(H,H) = 8.4 Hz, 2H; aromatic protons), 8.23 (t, J(H,H) = 8.1 Hz, 6H; aromatic protons), 8.09 (t, J(H,H) = 9.4 Hz, 6H; aromatic protons), 7.72 (d, J(H,H) = 8.5 Hz, 4H; aromatic protons), 7.40 (d, J(H,H) = 8.3 Hz, 4H; aromatic protons), 7.1 1 -6.34 (m, 20H; aromatic protons), 4.49 (broad m, 2H; CH), 3.85 (broad d, J(H,H) = 9.2 Hz, 2H; NH₂), 3.67 (broad t, J(H,H) = 9.0 Hz, 2H; NH₂); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 139.4-124.8 (m, aromatic carbon atoms), 63.8 (s; NCH); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 1 1 .2 ppm (s); elemental analysis (%) calculated for C₅8H₄8Cl2N₂OsP2: C 63.56, H 4.41 , N 2.56; found: C 63.07, H 4.25, N 2.54.

Example 16. Synthesis of irans-[OsCI₂((^-xylbinap)((fl,^-dpen)] (16)

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and (fl)-xylbinap (79 mg, 0.108 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (R,R)-dpen (23 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 ml_) was added to the product and again evaporated. Heptane (5 ml_) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. The product was then purified through silica gel (toluene) to remove traces of tri(m-tolyl)phosphine. Yield: 56 mg (47 %). ¹ H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.86 (t, J(H,H) = 6.9 Hz, 2H; aromatic protons), 8.16 (d, J(H,H) = 9.2 Hz, 4H; aromatic protons), 7.94-6.48 (m, 26H; aromatic protons), 5.94 (s, 2H; aromatic protons), 4.53 (broad m, 2H; NCH), 3.96 (broad m, 2H; NH₂), 3.84 (broad m, 2H; NH₂), 2.08 (s, 12H; CMe), 1 .82 ppm (s, 12H; CMe); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 135.2 - 123.9 (m; aromatic carbon atoms), 63.9 (s; NCH), 21 .5 (s; CMe), 21 .3 ppm (s; CMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 12.7 ppm (s); elemental analysis (%) calculated for C₆6H₆ CI₂N₂OsP₂: C 65.61 , H 5.34, N 2.32; found: C 65.47, H 5.12, N 2.25.

Example 17. Synthesis of irans-[OsCI₂((S)-xylbinap)((/^:?,/^:?)-dpen)] (17)

The irans-[OsCI₂((S)-xylbinap)((/^:?,/^:?)-dpen)] complex was prepared by following the procedure used for synthesising the trans-[OsC\₂{{R)-xy\b\nap){{R,R)-0pen)] (16) complex, but using the ligand (S)-xylbinap in place of the ligand (f?)-xylbinap. Yield: 60 mg (51 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.90 (t, J(H,H) = 8.0 Hz, 2H; aromatic protons), 8.20 (d, J(H,H) = 8.4 Hz, 4H; aromatic protons), 7.83- 6.48 (m, 26H; aromatic protons), 5.91 (s, 2H; aromatic protons), 4.66 (broad m, 2H; NCH), 4.58 (broad m, 2H; NH₂), 3.49 (broad m, 2H; NH₂), 2.04 (s, 12H; CMe), 1 .81 ppm (s, 12H; CMe); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 135.2 - 123.3 (m; aromatic carbon atoms), 63.8 (s; NCH), 21 .5 (s; CMe), 21 .3 ppm (s; CMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 13.3 ppm (s); elemental analysis (%) calculated for C₆6H₆ CI₂N₂OsP₂: C 65.61 , H 5.34, N 2.32; found: C 65.52, H 5.12, N 2.53.

Example 18. Synthesis of irans-[OsCI₂((/^:?,S)-josiphos^*)((/^:?,/^:?)-dpen)] (18)

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and (F?,S)-josiphos^* (76 mg, 0.107 mmol) were dissolved in toluene (1 mL) and the solution was refluxed at 120°C for 4 h. The ligand (F^-dpen (23 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 mL) was added to the product and again evaporated. Heptane (5 mL) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 mL) and dried under reduced pressure. Yield: 56 mg (48 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.44-6.73 (m, 14H; aromatic protons), 5.07-3.96 (broad m, 10H; CH, NH₂, PCH, C₅H₃), 3.88 (s, 5H; C₅H₅), 3.31 (s, 3H; OMe), 3.29 (s, 3H; OMe), 2.32 (s, 6H; CMe), 2.24 (s, 6H; CMe), 2.15-0.90 ppm (m, 25H; CH₂, Me); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 158.4 (d, J(C,P) = 2.2 Hz; COMe), 157.5 (d, J(C,P) = 2.3 Hz; COMe), 140.4 (d, J(C,P) = 1 .6 Hz; ipso Ph), 140.2 (d, J(C,P) = 1 .7 Hz; ipso Ph), 138.3 (d, J(C,P) = 1 .7 Hz; aromatic CMe), 138.1 (d, J(C,P) = 2.7 Hz; aromatic CMe), 135.2-127.2 (m; aromatic carbon atoms), 72.5 (s; FeC₅H₃), 70.6 (s; FeC₅H₅), 69.2 (d, J(C,P) = 7.7 Hz; FeC₅H₃), 67.0 (d, J(C,P) = 6.0 Hz; FeC₅H₃), 64.0 (s; NCH), 63.3 (s; NCH), 59.2 (s; OMe), 59.1 (s; OMe), 42.4 (d, J(C,P) = 25.2 Hz; PCH of Cy), 39.5 (d, J(C,P) = 19.5 Hz; PCH of Cy), 31 .8 (d; J(C,P) = 22.1 Hz; PCMe), 31 .7 - 27.2 (m; CH₂ of Cy), 21 .3 (s; Me), 16.6 ppm (d, J(C,P) = 8.5 Hz; PCMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = 2.0 (d, J(P,P) = 22.0 Hz), - 1 1 .6 ppm (d, J(P,P) = 22.0 Hz); elemental analysis (%) calculated for C₅6H₇₂CI₂FeN₂O₂OsP₂: C 56.80, H 6.13, N 2.37; found: C 57.12, H 5.96, N 2.09. Example 19. Synthesis of irans-[OsCI₂((/^:?)-xyllvleObiphep)((/^:?_!/^:?)-clach)] (19)

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and (F?)-xylMeObiphep (75 mg, 0.108 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (R,R)-dach (12 mg, 0.105 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 ml_) was added to the product and again evaporated. Heptane (5 ml_) was added to the product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. Yield: 69 mg (66 %). NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.01 (m, 6H; aromatic protons), 7.43-6.69 (m, 10H; aromatic protons), 5.98 (d, J(H,H) = 8.1 Hz, 2H; aromatic protons), 3.45 (m, 2H; NHH), 2.99 (s, 6H; OMe), 2.67 (m, 2H; NHH), 2.31 (m, 2H; CHN), 2.16 (s, 12H; CMe), 2.1 1 (s, 12H; CMe), 0.92 (m, 4H; CH₂), 0.49 ppm (m, 4H; CH₂); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): 158.2 (m; COMe), 136.8- 109.9 (m; aromatic carbon atoms), 57.0 (s; NCH), 54.2 (s; OMe), 35.5 (s; CH₂), 24.8 (s; CH₂), 21 .7 (s; CMe), 21 .2 ppm (s; CMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20 °C): δ = - 14.3 ppm (s); elemental analysis (%) calculated for C₅₂H₆₂CI₂N₂O₂OsP₂: C 58.36, H 5.84, N 2.62; found: C 59.00, H 5.87, N 2.84. Example 20. Synthesis of irans-[OsCI₂((/=?)-xylbinap)((/^:?,/^:?)-dach)] (20)

[Os₂CI₄(P(m-tolyl)₃)₅] (100 mg, 0.049 mmol) and (f?)-xylbinap (79 mg, 0.107 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (F^-dach (12 mg, 0.105 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 ml_) was added to the product and again evaporated. Heptane (5 ml_) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. Yield: 64 mg (59 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.85 (t, J(H,H) = 7.9 Hz, 2H; aromatic protons), 8.1 1 (d, J(H,H) = 7.41 Hz, 4H; aromatic protons), 7.91 -6.43 (m, 16H; aromatic protons), 5.95 (s, 2H; aromatic protons), 3.38 (m, 2H; NHH), 2.54 (m, 2H; NHH), 2.30 (m, 2H; CHN), 2.17 (s, 12H; Me), 1 .81 (s, 12H; Me), 0.89 (m, 4H; CH₂), 0.46 ppm (m, 4H; CH₂); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 135.2 - 123.3 (m; aromatic carbon atoms), 57.0 (s; NCH), 35.4 (s; CH₂), 24.8 (s; CH₂), 21 .7 (s; CMe), 21 .2 ppm (s; CMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 13.7 ppm (s); elemental analysis (%) calculated for C₅₈H₆₂CI₂N₂OSP₂: C 62.75, H 5.63, N 2.52; found: C 62.47, H 5.84, N 2.42.

Example 21 . Synthesis of irans-[OsCI₂((/^:?)-lvleObiphep)((/^:?)-daipen)] (21 )

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and (F?)-MeObiphep (63 mg, 0.108 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (f?)-daipen (34 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solution was concentrated (0.5 ml_) and on addition of heptane (5 ml_) the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. Yield: 70 mg (62 %). NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.19 (m, 8H; aromatic protons), 7.77 (t, J(H,H) = 8.3 Hz, 2H; aromatic protons), 7.64-6.65 (m, 22H; aromatic protons), 6.16 (d, J(H,H) = 8.5 Hz, 1 H; aromatic proton), 5.98 (d, J(H,H) = 8.7 Hz, 1 H; aromatic proton), 5.16 (broad d, J(H,H) = 1 1 .7 Hz, 2H; NH₂ and CHN), 4.88 (broad d, J(H,H) =10.6 Hz, 1 H; NH₂), 3.78 broad t, J(H,H) =12.4 Hz, 1 H; NH₂), 3.34 (s, 3H; OMe), 3.25 (m, 1 H; NH₂), 3.21 (s, 3H; OMe), 2.91 (s, 3H; OMe), 2.82 (s, 3H; OMe), 1 .77 (m 1 H; CHMe), 0.57 (d, J(H,H) = 6.8 Hz, 3H; CHMe), 0.01 ppm (d, J(H,H) = 6.8 Hz, 3H; CHMe); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 159.3 (s; COMe), 159.2 (s; COMe), 158.3 (d, J(C,P) = 1 1 .4 Hz, COMe), 158.0 (d, J(C,P) = 1 1 .6 Hz, COMe), 136.7- 1 10.1 (m; aromatic carbon atoms), 69.3 (s; NCAr), 64.4 (s; N CH), 54.8 (s; OMe), 54.7 (s; OMe), 54.4 (s; OMe), 54.1 (s; OMe), 28.6 (s; CHMe₂), 22.6 (s; CHMe), 16.1 ppm (s; CHMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 8.5 (d, J(P,P) = 16.0 Hz), -1 1 .5 ppm (d, J(P,P) = 16.0 Hz); elemental analysis (%) calculated for C₅₇H₅₈CI₂N₂O₄OsP₂: C 59.1 1 , H 5.05, N 2.42; found: C 59.54, H 4.83, N 2.44.

Example 22. Synthesis of irans-[OsCI₂((/=?)-binap)((/^:?)-daipen)] (22)

[Os₂CI₄(P(m-tolyl)₃)₅] (100 mg, 0.049 mmol) and (f?)-binap (67 mg, 0.108 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (f?)-daipen (34 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 ml_) was added to the product and again evaporated. Heptane (5 ml_) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. Yield: 69 mg (59 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.64 (t, J(H,H) = 8.0 Hz, 1 H; aromatic proton), 8.39-6.35 (m, 39H; aromatic protons), 4.99 (broad m, 2H; NH₂ and CHN), 4.43 (broad d, J(H,H) =10.8 Hz, 1 H; NH₂), 3.61 (broad t, J(H,H) =13.8 Hz, 1 H; NH₂), 3.35 (s, 3H; OMe), 3.25 (m, 1 H; NH₂), 3.19 (s, 3H; OMe), 1 .74 (m 1 H; CHMe), 0.52 (d, J(H,H) = 6.8 Hz, 3H; CHMe), 0.02 ppm (d, J(H,H) = 7.5 Hz, 3H; CHMe); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 159.3 (s; COMe), 159.2 (s; COMe), 136.3- 1 13.6 (m; aromatic carbon atoms), 69.3 (s; NCAr), 64.7 (s; N CH), 54.9 (s; OMe), 54.7 (s; OMe), 28.6 (s; CHMe), 22.6 (s; CHMe), 16.1 ppm (s; CHMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 9.81 (d, J(P,P) = 16.5 Hz), -1 1 .8 ppm (d, J(P,P) = 16.5 Hz); elemental analysis (%) calculated for C₆₃H₅₈CI₂N₂O₂OsP₂: C 63.15, H 4.88, N 2.34; found: C 63.58, H 4.89, N 2.55.

Example 23. Synthesis of frans-[OsCI₂((fl)-xylMeObiphep)((fl)-daipen)] (23)

[Os₂CI₄(P(m-tolyl)₃)₅] (100 mg, 0.049 mmol) and (f?)-xylMeObiphep (88 mg, 0.127 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (f?)-daipen (34 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 100°C for 45 min. The solvent was evaporated, heptane (5 ml_) was added to the product and again evaporated. Heptane (5 ml_) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. Yield: 79 mg (63 %). The product was obtained as a mixture of two diastereoisomers (trans isomer = 80%). ³¹ P{¹ H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 10.4 (d, J(P,P) = 16.5 Hz), - 10.8 (d, J(P,P) = 15.0 Hz; minor isomer), -13.2 (d, J(P,P) = 15.0 Hz; minor isomer), -13.8 ppm (d, J(P,P) = 16.5 Hz); elemental analysis (%) calculated for C₆5H₇ CI₂N₂O₄OsP₂: C 61 .46, H 5.87, N 2.21 ; found: C 62.14, H 5.69, N 2.29.

Example 24. Synthesis of irans-[OsCI₂((/^:?)-xylbinap)((/^:?)-daipen)] (24)

[Os₂CI₄(P(m-tolyl)₃)₅] (100 mg, 0.049 mmol) and (f?)-xylbinap (86 mg, 0.1 18 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (f?)-daipen (34 mg, 0.108 mmol) was added at room temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (5 mL) was added to the product and again evaporated. Heptane (5 mL) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 mL) and dried under reduced pressure. Yield: 75 mg (58 %). ¹H NMR (200.1 MHz, C₆D₆, 20°C): δ = 8.93 (t, J(H,H) = 8.3 Hz, 1 H; aromatic proton), 8.74 (t, J(H,H) = 7.9 Hz, 1 H; aromatic proton), 8.17-6.31 (m, 28H; aromatic protons), 5.93 (d, J(H,H) = 12.2 Hz, 2H; aromatic protons), 4.95 (broad m, 2H; NH₂ and CHN), 4.28 (broad d, J(H,H) = 8.8 Hz, 1 H; NH₂), 3.61 (broad m, 1 H; NH₂), 3.36 (s, 3H; OMe), 3.29 (m, 1 H; NH₂), 3.19 (s, 3H; OMe), 2.13 (s, 6H; CMe), 2.00 (s, 6H; CMe), 1 .77 (s, 6H; CMe), 1 .76 (s, 6H; CMe), 1 .66 (m 1 H; CHMe), 0.51 (d, J(H,H) = 6.8 Hz, 3H; CHMe), 0.02 ppm (d, J(H,H) = 6.5 Hz, 3H; CHMe); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 159.2 (s; COMe), 136.3 - 1 13.4 (m; aromatic carbon atoms), 69.3 (s; NCAr), 64.5 (s; NCH), 54.8 (s; OMe), 54.6 (s; OMe), 28.4 (s; CHMe), 22.6 (s; CHMe), 21 .5 (s; CMe), 21 .2 (s; CMe), 15.9 ppm (s; CHMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 13.1 ppm (d, J(P,P) = 16.5 Hz), -14.6 ppm (d, J(P,P) = 16.5 Hz); elemental analysis (%) calculated for C₇₁ H₇₄CI₂N₂O₂OsP₂: C 65.08, H 5.69, N 2.14; found: C 65.61 , H 5.83, N 1 .99. Example 25. Synthesis of trans-[OsC\₂{{R,R)-skewphos){{R,R)-0pen)] (25)

[OsCI₂(PPh₃)₃] (200 mg, 0.191 mmol) and (fl^-skewphos (101 mg, 0.229 mmol) were dissolved in toluene (1 .5 mL) and the solution was refluxed at 120°C for 4 h. The ligand (F^-dpen (45 mg, 0.210 mmol) was added at room temperature and the solution was refluxed at 100°C for 45 min. The solvent was evaporated and on addition of ethyl ether (3 mL) the formation of a yellow precipitate was observed, which was filtered off and washed with ethyl ether (3x2 mL). The solution was dried under reduced pressure to obtain a brown oil. The product was treated with heptane (2 mL) and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 mL) and dried under reduced pressure. Yield: 70 mg (40%). The product was obtained as a mixture of two diastereoisomers {trans isomer > 65 %). NMR (200.1 MHz, C₆D₆, 20°C): δ = 7.86- 6.72 (m; aromatic protons), 4.53 - 3.10 (m; NCH, NH_2, PCH), 2.20-0.70 ppm (m; CH₂, CH₃); ¹³C{¹H} NMR (50.3 MHz, C₆D₆, 20°C for the major isomer): δ = 139.8- 126.5 (m; aromatic carbon atoms), 63.9 (s; NCH), 38.3 (s; CH₂), 18.9 ppm (s; CH₃); ³¹ P{¹ H} NMR (81 .0 MHz, C₆D₆, 20°C): δ 0.54 (d, J(P,P) = 17.3 Hz; minor isomer), - 10.6 (s), -1 1 .7 ppm (d, J(P,P) = 17.3 Hz; minor isomer); elemental analysis (%) calculated for C₄₃H₄6Cl2N₂OsP2: C 56.51 , H 5.07, N 3.07; found: C 56.1 1 , H 4.97, N 3.16.

Example 26. Synthesis of irans-[OsCI₂((S)-xylbinap)((/^:?,/^:?)-dppn)] (26)

[Os₂CI₄(P(m-tolyl)₃)5] (100 mg, 0.049 mmol) and (S)-xylbinap (86 mg, 0.1 17 mmol) were dissolved in toluene (1 ml_) and the solution was refluxed at 120°C for 4 h. The ligand (F^-dppn (24 mg, 0.106 mmol) was added at ambient temperature and the solution was refluxed at 120°C for 1 h. The solvent was evaporated, heptane (3 ml_) was added to the product and again evaporated. Heptane (3 ml_) was added to the obtained product and the formation of a yellow precipitate was observed. The solid was filtered off, washed with heptane (2x3 ml_) and dried under reduced pressure. The product was then purified through silica gel (toluene) to remove traces of tri(m-tolyl)phosphine. Yield: 59 mg (49 %). ¹ H NMR (200.1 MHz, C₆D₆, 20°C): δ = 9.01 (t, J(H,H) = 8.1 Hz, 2H; aromatic protons), 8.03 (d, J(H,H) = 7.1 Hz, 4H; aromatic protons), 7.89-6.31 (m, 26H; aromatic protons), 5.88 (s, 2H; aromatic protons), 4.77 (broad m, 2H; NCH), 3.44-3.24 (broad m, 4H; NH₂), 2.01 -1 .77 ppm (m, 26H; CMe); ¹³C{¹ H} NMR (50.3 MHz, C₆D₆, 20°C): δ = 135.2 - 123.3 (m; aromatic carbon atoms), 50.2 (s; NCH), 39.8 (s; CH₂), 21 .4 (s; CMe), 21 .1 ppm (s; CMe); ³¹ P{¹H} NMR (81 .0 MHz, C₆D₆, 20°C): δ = - 13.1 ppm (s); elemental analysis (%) calculated for C₆₇H₆₆CI₂N₂OsP₂: C 65.84, H 5.44, N 2.29; found: C 65.54, H 4.67, N 2.51 .

B. Catalytic tests with the osmium(ll) complexes

The osmium(ll) complexes of the present invention can be used for preparing alcohols starting from the corresponding ketones or aldehydes, by hydrogenation or hydrogen transfer reactions. In the presence of the new osmium-based catalysts and a base such as an alkali metal alkoxide, various alcohols can be obtained by reduction of R⁹C(=0)R¹⁰ cyclic ketones, linear dialkyls, alkylary I ketones and diarylketones where R⁹ and R¹⁰ represent a saturated or unsaturated aliphatic group, or an aryl group, which can have or not have alkyl substituent groups, substituent groups containing oxygen, halogen atoms, or a heterocyclic group. By utilizing the same catalysts, R⁹C(=0)H aldehydes can also be reduced to alcohols.

The experimental conditions employed in the various catalytic tests are described in detail in the examples given below.

B1. Non-asymmetric reduction of ketones and aldehydes by hydrogenation

All the procedures were carried out under hydrogen atmosphere, using previously distilled ethanol.

Example 27. Catalytic reduction of acetophenone in the presence of osmium(ll) complexes

The process for acetophenone reduction catalyzed by the complex (2) is described. The same method was used with the complexes (3-8) and the results are presented in table 3.

a) Reduction of acetophenone catalyzed by the complex (2)

The catalyst solution was prepared in a 10 ml flask with side arm (Schlenk), adding 2 ml of ethanol to the complex (2) (1 .5 mg, 1 .71 μηιοΙ). By means of stirring, the complex dissolved completely in a few minutes.

Separately, in a 25 ml flask with side arm (Schlenk), 0.17 ml of NaOEt (0.25 M, 0.043 mmol) and 0.5 ml_ of the previously prepared solution containing the catalyst were added to a solution of previously distilled acetophenone (0.5 ml_, 4.30 mmol) in ethanol (7.4 ml). The entire mixture was then drawn off into a reactor temperature-controlled at 70 °C. Molecular hydrogen (H₂) was introduced at a pressure of 5 bar. The hydrogen addition was considered the start time of the reaction. The acetophenone/catalyst/NaOEt molar ratio was 10000/1 /100 and the substrate concentration was 0.5 M. The data for the gas chromatographic analyses are presented in table 3.

Example 28. Reduction of ketones and aldehydes by hydrogenation with the complex (2).

The process for ketone and aldehyde reduction catalyzed by the complex (2) at 60 °C was analogous to that described in example 27 for acetophenone reduction and the results are presented in table 4.

B2. Asymmetric reduction of ketones by hydrogenation

All the procedures were performed under hydrogen atmosphere, using previously distilled ethanol.

Example 29. Catalytic reduction of acetophenone by hydrogenation in the presence of the complex (16)

The reduction of acetophenone catalyzed by the complex (16) is described. The same method was used with the complexes (9)-(26) and the results are presented in table 5.

The catalyst solution was prepared in a 10 ml flask with side arm (Schlenk), adding 2 ml of ethanol to the complex (16) (2.0 mg, 1 .7 μηιοΙ). By means of agitation, the complex dissolved completely in a few minutes.

Separately, in a 25 ml flask with side arm (Schlenk), 0.17 mL of NaOEt (0.25 M, 0.043 mmol) and 0.5 mL of the previously prepared solution containing the catalyst were added to a solution of previously distilled acetophenone (0.5 mL, 4.30 mmol) in ethanol (7.4 mL). The entire mixture was then drawn off into a reactor temperature-controlled at 60 °C. Molecular hydrogen (H₂) was introduced at a pressure of 5 bar. The hydrogen addition was considered the start time of the reaction. The ketone/catalyst/NaOEt molar ratios were 10000/1 /100 and the substrate concentration was 0.5 M. The data for the gas chromatographic analyses are presented in table 5.

Example 30. Catalytic reduction of ketones by hydrogenation in the presence of the complexes (16, 17).

The process of ketone and aldehyde reduction catalyzed by the complex (16) was analogous to that described in example 29 for acetophenone reduction and the results are presented in table 6.

Table 6. Catalytic reduction of ketones (0.5 M) in the presence of the complexes (16, 17). S/C ratio = 10000, NaOEt = 1 mol %. The reaction was conducted in ethanol at 60 °C at a 5 bar H₂ pressure

Example 31 . Catalytic reduction of acetophenone in the presence of the complexes (18) and (25) prepared in situ

The process of acetophenone reduction catalyzed by the complex (18) is described. The same method was used for the complex (25) and the results are presented in table 7.

The catalyst was prepared in a 10 ml flask with side arm (Schlenk), adding 0.5 ml of toluene to the complex (1 ) (2.6 mg, 2.5 μηιοΙ) and to the phosphine {R,S)- josiphos* (2.2 mg, 3.1 μηποΙ) and the entire mixture was refluxed for 3-4 hours. (R,R)-dpen (0.7 mg, 3.3 μηιοΙ) was then added and the solution was held at 100°C for 1 -2 hours. Finally, 2.5 ml of ethanol were added.

Separately, in a 25 ml flask with side arm (Schlenk), 0.34 ml of NaOEt (0.25 M, 0.085 mmol) and 0.5 mL of the previously prepared solution containing the catalyst were added to a solution of previously distilled acetophenone (0.5 ml_, 4.30 mmol) in ethanol (7.2 ml). The entire mixture was then drawn off into a reactor temperature-controlled at 70 °C. Molecular hydrogen (H₂) was introduced at a pressure of 5 bar. The hydrogen addition was considered the start time of the reaction. The acetophenone/catalyst/NaOEt molar ratios were 10000/1 /200 and the substrate concentration was 0.5 M. The data for the gas chromatographic analyses are presented in table 7.

Table 7. Catalytic reduction of acetophenone (0.5 M) in the presence of the complex (18) and (25) prepared in situ. The acetophenone/complex/NaOEt molar ratio was 10000/1 /200. The reaction was conducted in ethanol at 70 °C at a 5 bar

B3 Reduction of ketones by hydrogen transfer

All the procedures were performed under argon atmosphere, using previously deaerated and distilled 2-propanol.

Example 32. Catalytic reduction of acetophenone in the presence of the complexes (2), (9) and (11 ).

The process of acetophenone reduction catalyzed by the complex (2) is described. The same method was used for the complexes (9) and (11 ) and the results are presented in table 8.

The catalyst solution was prepared in a 10 ml flask with side arm (Schlenk), adding 2 ml of 2-propanol to the complex (2) (1 .80 mg, 2.1 μηιοΙ). By means of agitation, the complex dissolved completely in a few minutes.

Separately, in a 50 ml flask with side arm (Schlenk), 1 ml_ of the previously prepared solution containing the catalyst and 0.4ml_ of a 0.1 M NaO/Pr solution (0.04 mmol) in 2-propanol were added under reflux to a solution of acetophenone (240 μΙ_, 2.06 mmol) in 18.6 ml_ of 2-propanol. The complex addition was considered the start time of the reaction. The acetophenone/catalyst/NaO/Pr molar ratio was 2000/1 /50 and the substrate concentration was 0.1 M.

Claims

Claims

1 . Osmium(l l) complexes represented by the general formula (I)

wherein :

X, L, U can be:

X independently of each other a halogen, an alkoxy (OY) (Y = C-|-C₇ alkyl group optionally substituted) and a hydrogen atom ;

L a phosphine ligand selected from the groups:

a) a non-chiral bidentate phosphine selected from the group consisting of 1 ,4-bis(diphenylphosphino)butane (dppb), 1 , 1 '- bis(diphenylphosphino)ferrocene (dppf) and bis[2- (diphenylphosphino)phenyl]methanone (dpbp);

b) a chiral bidentate phosphine selected from the group consisting of (F?)-(6,6'-dimethoxybiphenyl-2,2'- diyl)bis(diphenylphosphine) [(/=?)-MeObiphep], (fl)-(6,6'- dimethoxybiphenyl-2,2'-diyl)bis[bis(3,5-dimethylphenyl)phosphine] [(fl)-3,5-xylMeObiphep], (S)-(6,6'-dimethoxybiphenyl-2,2'- diyl)bis(diphenylphosphine) [(S)-MeObiphep], (Α)-(1 .1 '- binaphthalene-2,2'-diyl)bis(diphenylphosphine) [(f?)-binap], (f?)-(1 , 1 '- binaphthalene-2,2'-diyl)bis[bis(3,5-dimethylmethyl)phosphine] [(R)- 3,5-xylbinap], (S)-(1 , 1 '-binaphthalene-2,2'-diyl)bis[bis(3,5- dimethylphenyl)phosphine] [(S)-3,5-xylbinap], (fl)-1 -{(S)-2-[bis(3,5- dimethyl-4-methoxyphenyl)phosphine]ferrocenyl}

ethyldicyclohexylphosphine [(f?, S)-josiphos*] and (2f?,4/^:?)-2,4- bis(diphenylphosphine)pentane [(R, R)-bdpp\ ;

L' a diamine bidentate ligand represented by the general formula (I I)

wherein R⁵, R⁶, R⁷ and R⁸ and the R¹ - R⁴ groups can be equal to or different from each other and can be hydrogen atoms, linear or branched aliphatic groups, C1-C20 alkyls or C₂-C₂o alkenyls, C3-C20 cycloaliphatic groups and C₆-C₂2 aryl groups and wherein at least one among R⁵, R⁶, R⁷ and R⁸ is hydrogen, and the bridged group G can be a single bond or a -(CR'R")_X- chain with x equal to 1 or 2 where R' and R" can be equal to or different from each other and are H, saturated or unsaturated linear or branched aliphatic groups, cycloaliphatic groups, and aryl groups having the aforementioned meanings for R¹ - R⁸.

2. Osmium(l l) complexes according to claim 1 , wherein the ligand U is selected from the group consisting of ethylenediamine (en), 1 ,3-propanediamine (pn), 1 ,4-butanediamine (bn), 1 ,2-diaminocyclohexane (dach), N,N-dimethyl- ethylenediamine (Ν,Ν-dimen), {R, R}^ ,2-diphenylethylenediamine [(R,R)-0pen], {R, R)^ ,2-diaminocyclohexane [{R, R)-0ach], {R, Ry\ ,3-diphenylpropanediamine [{R, R)-0ppn] and (f?)-1 , 1 -dianisyl-2-isopropyl-1 ,2-ethylenediamine [(f?)-daipen).

3. Osmium(l l) complexes according to claim 1 , wherein the ligand X is selected from the group consisting of chlorine, bromine, hydrogen and OCH₂CF₃.

4. Osmium(l l) complexes according to any one of claims 1 -3 having a cis and/or trans configuration.

5. Method for preparing osmium(l l) complexes according to claim 1 , comprising at least the steps of :

a) selecting an osmium precursor from the complexes of formula [OsX₂(PAr₃)₃] (Ar = Ph, p-tolyl), [Os₂X₄(P(m-tolyl)₃)₅] and OsX₂("Hgand'), wherein the "Hgand" is selected from benzene, p-cymene, cyclooctadiene, and wherein in said precursors X has the meanings defined in claim 1 for the osmium(l l) complexes;

b) reacting said precursor in an organic solvent at temperatures comprised between 40 °C and 1 20 °C with the diphosphine ligand L, and then in the same reaction mixture with the diamine ligand U, both ligands being added in amounts in excess of the reaction stoichiometry.

6. Method for preparing osmium(l l) complexes according to claim 5, comprising a further treatment of the reaction mixture, either before or after the reaction step b) between the precursor and the selected ligands L and/or U, for the partial or complete replacement of the ligand X when the ligand X of the precursor is partially or completely different from the ligand X of the osmium complex to be prepared.

7. Method for preparing osmium(ll) complexes according to claims 5 and 6, wherein the precursors are selected from [Os₂CI₄(P(m-tolyl)₃)5] and [OsCI₂(PPh₃)₃].

8. Method for preparing osmium(ll) complexes according to any one of claims 5-7, comprising the further steps of:

preparing and separating the precursor as intermediate of the osmium(ll) complexes;

separating and purifying the obtained osmium(ll) complexes from the reaction mixture.

9. The complex [Os₂CI -tolyl)₃)5] represented by the structural formula

wherein P is P m-tolyl)₃.

10 Use of osmium(ll) complexes according to any one of claims 1 -4 as catalysts in the symmetric or asymmetric reduction reactions of carbonyl compounds.

1 1 . Use of osmium(ll) complexes according to claim 10, wherein the reduction reaction of said carbonyl compounds is by hydrogenation or by hydrogen transfer.

12. Use of osmium(ll) complexes according to any one of claims 1 -4 as catalysts in the reduction reactions of carbonyl compounds obtained in situ during said reduction reaction.