Method for producing amines by homogeneously catalyzed reductive amination of carbonyl compounds

The invention relates to the preparation of amines by reaction of aldehydes or ketones with ammonia or primary or secondary amines in the presence of hydrogen and in the presence of homogeneous metal catalysts under mild conditions. Metal catalysts which can be used are complexes of late transition metals with phosphorus-containing ligands. The process of the invention also makes possible the synthesis of enantiomerically pure or enantiomerically enriched amines by means of an enantioselective or diastereoselective reaction.

Racemic and enantiomerically pure amines play a dominant role in numerous complex natural substances, for example alkaloids, vitamins or amino acids, whose chemical, pharmaceutical and industrial importance is undisputed. As chemical intermediates amines are employed in, for example, the synthesis of pharmaceuticals, agrochemicals, food additives, dyes or cosmetics. In the field of active compounds, amino acids and amino alcohols play a predominant role.

Heterogeneously catalyzed amination of ketones and aldehydes plays an important role in the synthesis of unfunctionalized and functionalized amines (Catalytic Hydrogenation over Platinum Metals, Academic Press, New York, 1967, p. 291 ff; Catalytic Hydrogenation in Organic Synthesis, Academic Press, New York, 1979, 165 ff). Heterogeneous catalysts which have been used are, for example, CuCr 2 O 4 ·CuO (Kurc et al., Chem. Prum. 1987, 37, 26), Re or Cu (DE-A-19631521), Raney nickel (EP-A0011401), Ru supported on MgO/Al 2 O 3 (DE-A-4010252), Ru supported on γ—Al 2 O 3 (EP-A-0449089), Cu supported on Al 2 O 3 (Barrault et al., Rev. Fr. Corps Gras 1991, 38, 103) or Fe (CA-A-0907059).

However, a heterogeneous reaction has, in principle, considerable disadvantages (J. Hagen, Technische Katalyse, VCH, Weinheim, 1996, p. 10). It has been found that characteristic problems occur in the mass transfer between the phases and result in an appreciable reduction in the reaction rate. For this reason, high reaction temperatures of up to 150° C. and pressures of up to 250 bar are usually necessary for the heterogeneously catalyzed amination. This represents a considerable economic disadvantage in the construction and operation of such plants. The development of new catalysts which make it possible to carry out the desired reaction under milder conditions is therefore of exceptional interest. Furthermore, tolerance of further functional groups which are usually present in the molecule, e.g. in the synthesis of active compounds, is significantly restricted because of the drastic reaction conditions. In addition, the heterogeneous catalysts can be characterized only with difficulty, a fact which can seriously impair the reproducibility of the catalysis results and make rational catalyst design or modification to meet specific objectives difficult or even impossible.

Only very few examples of catalysts in homogeneous systems are known in the literature: dimethylglyoximate complexes of cobalt and rhodium (M. V. Klyuev, M. L. Khidekel, Transition Met. Chem., 1980, 5 134-139). To activate the catalysts, almost stoichiometric amounts of sodium borohydride have to be used. Furthermore, Rh and Co carbonyl complexes (L. Marko, J. Bakos Journal of Organometallic Chemistry, 1974, 81, 411-414) and cobalt-cyano-complexes (M. Murakami, J.-W. Kang Bull. Chem. Soc. Japan, 1963, 36, 763-768) have been described. However, owing to the large amounts of catalyst and the drastic conditions required, the processes described are not practical.

JP 11-343269 describes the synthesis of octylamine from octanal and ammonia, in which a series of homogeneous catalysts such as iron(II) sulfide, nickel acetylacetonate, carbonylrhodium acetylacetonate, palladium acetylacetonate, dodecacarbonylosmium(III), hexacarbonylindium(VI), 1,5-cyclooctadieneplatinum dichloride and ruthenium acetylacetonate with 2,2′-bipyridyl in an extremely complicated process at a high temperature of 150° C. The hydroaminomethylation reaction (P. Eilbracht et al. Chem. Rev. 1999, 99, 3329-3364), for which a reductive amination of an intermediate has been postulated but not proven to date, also proceeds under drastic reaction conditions.

It is therefore an object of the present invention to find a process by means of which the amination can be carried out under mild conditions and the abovementioned problems can be avoided.

Furthermore, the process should also allow the synthesis of enantiomerically pure or enantiomerically enriched amines by use of chirally modified catalysts.

It has now surprisingly been found that the desired amines can be obtained very efficiently by the reductive amination of ketones and aldehydes in the presence of catalytically active transition metal complexes based on phosphorus-containing ligands under very mild conditions.

Under these mild reaction conditions, an enantioselective reaction is possible when using chiral ligands.

The transition metal catalysts used give good to very good yields of the desired amine in the reductive amination. At the same time, a very high amine/alcohol ratio in the products can be achieved.

The process of the invention overcomes the known disadvantages of the metal-catalyzed reductive aminations described hitherto.

The present invention accordingly provides a process for preparing amines of the formula (III)

by reacting a compound of the formula (I)

with a compound of the formula (II)

where the radicals R 1 to R 4 are selected independently from the group consisting of hydrogen, (C 1 -C 24 )-alkyl, (C 2 -C 24 )-alkenyl, (C 2 -C 24 )-alkynyl, (C 6 -C 10 )-aryl, CF 3 , CN, COOH, COOM, where M is a cation, CHO, SO 3 H, COO-alkyl-(C 1 -C 8 ), CONH 2 , CONHalkyl-(C 1 -C 8 ), CONalkyl 2 -(C 1 -C 8 ), CO-alkyl-(C 1 -C 8 ), CO-phenyl, COO-phenyl, COO-aryl-(C 6 -C 10 ), CO-aryl-(C 6 -C 10 ), P(aryl) 2 , Palkyl 2 —(C 1 -C 8 ), PO(aryl) 2 , POalkyl 2 -(C 1 -C 4 ), PO 3 H 2 , POalkyl-(C 1 -C 4 )(O-alkyl-(C 1 -C 6 )), PO(O-alkyl-(C 1 -C 6 )) 2 , SO 3 -alkyl-(C 1 -C 4 ), SO 2 -alkyl-(C 1 -C 6 ), SO-alkyl-(C 1 -C 6 ) or Si(alkyl) 3 —(C 1 -C 8 ), and/or R 3 and R 4 are selected independently from the group consisting of O-alkyl-(C 1 -C 8 ), OCO-alkyl-(C 1 -C 8 ), O-aryl, fluorine, OH, NH 2 , NH-alkyl-(C 1 -C 8 ), N-alkyl 2 -(C 1 -C 8 ), NHCO-alkyl-(C 1 -C 4 ), NHaryl-(C 6 -C 10 ), NHCOO-alkyl-(C 1 - 4 ),

where alkyl is, for the purposes of the present invention, an unbranched or branched aliphatic or cyclic or heterocyclic radical containing at least one (1-4) nitrogen, sulfur or oxygen atom, alkenyl is an olefinic hydrocarbon, alkynyl is an acetylenic hydrocarbon and aryl is an aromatic radical which may also be an aromatic containing at least one (1-4) nitrogen, sulfur or oxygen atom. Alkyl, alkenyl, alkynyl and also aryl may bear substituents selected independently from among hydrogen, O-alkyl-(C 1 -C 8 ), OCO-alkyl-(C 1 -C 8 ), O-phenyl, phenyl, aryl(C 6 -C 10 ), fluorine, chlorine, bromine, iodine, OH, NO 2 , CF 3 , CN, COOH, COOM, where M is a cation (Li + , Na + , K + , Mg 2+ , Ca 2+ , NH 4 + , N(C 1 -C 10 -alkyl) 4 + , N(C 1 -C 10 alkyl/C 6 -C 10 -aryl) 4 + ), CHO, SO 3 H, NH 2 , NH-alkyl-(C 1 -C 8 ), N-alkyl 2 -(C 1 -C 8 ), NHCO-alkyl-(C 1 -C 4 ), COO-alkyl-(C 1 -C 8 ), CONH 2 , CO-alkyl-(C 1 -C 8 ), NHCOH, NHCOO-alkyl-(C 1 -C 4 ), CO-phenyl, COO-phenyl, COO-aryl-(C 6 -C 10 ), CO-aryl-(C 6 -C 10 ), CHCH—CO 2 -alkyl-(C 1 -C 8 ), P(aryl) 2 , CHCHCO 2 H, P-alkyl 2 -(C 1 -C 8 ), PO-aryl 2 , POalkyl 2 -(C 1 -C 4 ), PO 3 H 2 , POalkyl-(C 1 -C 4 )(O-alkyl-(C 1 -C 6 )), PO(O-alkyl-(C 1 -C 6 )) 2 , SO 3 -alkyl-(C 1 -C 4 ), SO 2 -alkyl-(C 1 -C 6 ), SO-alkyl-(C 1 -C 6 ) or Si(alkyl) 3 —(C 1 -C 8 ).

Both R 1 and R 2 and also R 3 and R 4 can be linked by covalent bonds so that R 1 and R 2 and/or R 3 and R 4 in each case form a four- to eight-membered ring. R 1 or R 2 may also be part of an organometallic compound.

The reaction is carried out in the presence of hydrogen and a homogeneous catalyst system comprising at least one metal atom selected from the group consisting of Rh, Ru, Ir, Pd, Pt, Co and Ni and one or more monodentate or bidentate achiral or chiral ligands of the formula (IV) or (V)

(R 6 Y 1 )(R 7 Y 1 )P 1 X 1 ZX 2 P 2 (Y 2 R 8 )(Y 2 R 9 )  (IV)

(R 6 Y 1 )(R 7 Y 1 )(R 8 Y 1 )P  (V)

where

R 6 to R 9 are identical or different and are a hydrogen atom or a C 1 -C 50 group, e.g. C 1 -C 24 -alkyl, C 2 -C 20 -alkenyl, C 3 -C 8 -cycloalkyl, C 5 -C 8 -cycloalkenyl, C 6 -C 14 -aryl, phenyl, naphthyl, fuorenyl, C 2 -C 13 -heteroaryl, where the number of heteroatoms from the groups consisting of N, O, S can be 1-4, where the cyclic aliphatic or aromatic radicals are preferably 5- to 7-membered rings,

and in which all the abovementioned substituents may each be substituted by one or more substituents selected independently from among hydrogen, C 1 -C 20 -alkyl, C 2 -C 20 -alkenyl, C 1 -C 10 -haloalkyl, C 3 -C 8 -cycloalkyl, C 5 -C 8 -cycloalkenyl, C 2 -C 9 -heterocycloalkyl, C 1 -C 9 -heterocyclo-alkenyl, C 6 -C 14 -aryl, phenyl, C 2 -C 13 -heteroaryl, where the number of heteroatoms from the group consisting of N, O, S can be 1-4, C 1 -C 10 -alkoxy, OCO-alkyl-(C 1 -C 8 ), O-aryl-(C 5 -C 10 ), O-phenyl, C 1 -C 9 trihalomethylalkyl, fluoro, chloro, bromo, iodo, nitro, hydroxy, trifluoromethylsulfonato, oxo, thio, thiolato, amino, C 1 -C 8 -substituted amino of the types mono- and di-C 1 -C 8 -alkylamino or C 2 -C 8 -alkenylamino or mono-, di-, tri-C 6 -C 8 -arylamino or C 1 -C 8 -alkyl-C 6 -C 10 -arylamino, NH—CO-alkyl-C 1 -C 8 , NH—CO-aryl-C 6 -C 8 , cyano, C 1 -C 8 -acyloxy, carboxyl, carboxylato of the formula COOR 12 , sulfinato, sulfonato of the formula SO 3 R 12 , phosphonato of the formula PO 3 H 2 , PO 3 HR 12 , PO 3 R 12 2 , where R 12 is either a monovalent cation, NH 4 + , N(C 1 -C 10 -alkyl) 4 + , N(C 1 -C 10 -alkyl/C 6 -C 10 -aryl) 4 +, C 1 -C 18 -alkyl or C 6 -aryl, tri-C 1 -C 6 -alkylsilyl, and where two of these substituents may also be bridged, and R 6 and R 7 and/or R 8 and R 9 may also be linked by a covalent bond so as to form a cyclic compound having from four to eight atoms,

X 1 and X 2 are each, independently of one another, a direct phosphorus-carbon bond, O, S or NR 10 , where R 10 corresponds to one of the radicals defined for R 6 -R 9 , Y 1 and Y 2 is a direct phosphorus-carbon bond, —O— or —NR 11 —, where R 11 corresponds to one of the radicals defined for R 6 -R 9 , Z corresponds to 1-6 carbon atoms which are bound to one another by single or multiple bonds and connect the unit (R 6 Y 1 )(R 7 Y 1 )PX 1 to the unit X 2 P(Y 2 R 8 )(Y 2 R 9 ), where Z may be part of an aliphatic, cycloaliphatic, olefinic, cycloolefinic system which may contain from one to four heteroatoms from the group consisting of N, O, S, a metallocene, in particular a ferrocene, a 1,1′-disubstituted ferrocene, 1-(1-ethylenyl)-2-ferrocenyl or a 1,2-disubstituted ferrocene, or one or more aromatic or heteroaromatic ring systems, where the ring system comprises a total of from 2 to 14 carbon atoms which may be monosubstituted or polysubstituted by substituents as specified for R 6 -R 9 or directly by C 1 -C 10 -alkoxy, OCO-alkyl-(C 1 -C 8 ), O-aryl-(C 5 -C 10 ), O-phenyl, C 1 -C 9 -trihalomethylalkyl, trifluoromethyl, trichloromethyl, fluoro, chloro, bromo, iodo, nitro, hydroxy, trifluoromethylsulfonato, oxo, thio, thiolato, amino, C 1 -C 8 -substituted amino of the formulae NH 2 , NH-alkyl-C 1 -C 8 , NH-aryl-C 5 -C 6 , N-alkyl 2 —C 1 -C 8 , N-aryl 2 -C 5 -C 6 , N-alkyl 3 —C 1 -C 8 + , N-aryl 2 —C 5 -C 6 -aryl-C 5 -C 6 + , C 1 -C 6 -acyloxy, carboxylato of the formulae COOH and COOR 12 , sulfinato, sulfonato of the formulae SO 3 H and SO 3 R 12 , phosphonato of the formulae PO 3 H 2 , PO 3 HR 12 and PO 3 R 12 2 , where R 12 is either a monovalent cation, NH 4 + , N(C 1 -C 10 -alkyl) 4 + , N(C 1 -C 10 -alkyl/C 6 -C 10 -aryl) 4 + , C 1 -C 8 -alkyl or C 6 -aryl, C 1 -C 6 -trialkylsilyl, NHCO-alkyl-(C 1 -C 4 ), COO-alkyl-(C 1 -C 8 ), CONH 2 , CON(alkyl-(C 1 -C 8 )) 2 , CO-alkyl-(C 1 -C 8 ), CO-alkenyl-(C 1 -C 8 ), NHCOO-alkyl-(C 1 -C 4 ), CO-aryl-(C 6 -C 10 ), CO-phenyl, COO-aryl-(C 6 -C 10 ), COO-phenyl, CHCH—CO 2 -alkyl-(C 1 -C 8 ), CHCHCO 2 H, and P is a trivalent phosphorus atom.

In a preferred embodiment, R 1 to R 4 are each, independently of one another, hydrogen, (C 1 -C 12 )-alkyl, (C 2 -C 12 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 6 -C 10 )-aryl, CF 3 , CN, COOH, COOM, where M is a cation (Li + , Na + , K + , Mg 2+ , Ca 2+ , NH 4 + , N(C 1 -C 10 -alkyl) 4 + , N(C 1 -C 10 -alkyl/C 6 -C 10 -aryl) 4 + ), COO-alkyl-(C 1 -C 8 ), CONH 2 , CO-alkyl-(C 1 -C 8 ), CO-phenyl, COO-phenyl, COO-aryl-(C 6 -C 10 ), CO-aryl-(C 6 -C 10 ), PO(aryl-C 6 -C 10 ) 2 , POalkyl 2 -(C 1 -C 4 ), PO 3 H 2 , PO(alkyl-(C 1 -C 4 ))(O-alkyl-(C 1 -C 4 )), PO(O-alkyl-(C 1 -C 6 )) 2 or Si(alkyl) 3 -(C 1 -C 8 ) and/or R 3 and R 4 are selected independently from the group consisting of O-alkyl-(C 1 -C 8 ), OCO-alkyl-(C 1 -C 8 ), O-aryl(C 6 -C 10 ), OH, NH 2 , NH-alkyl-(C 1 -C 8 ), N-alkyl 2 -(C 1 -C 8 ), NHCO-alkyl-(C 1 -C 4 ), NHCOO-alkyl-(C 1 -C 4 ),

where alkyl is an unbranched or branched aliphatic or cyclic or heterocyclic (containing at least one nitrogen or oxygen atoms (1-4)) radical, alkenyl is an olefinic hydrocarbon, alkynyl is an acetylenic hydrocarbon and aryl is an aromatic radical which may also be an aromatic containing at least (1-4) one nitrogen, oxygen and/or sulfur atom. Alkyl, alkenyl and alkynyl and also aryl may bear substituents selected independently from among hydrogen, O-alkyl-(C 1 -C 8 ), OCO-alkyl-(C 1 -C 8 ), O-phenyl, phenyl, aryl-C 6 -C 10 , fluorine, chlorine, bromine, iodine, OH, NO 2 , Si-alkyl 3 -(C 1 -C 8 ), CF 3 , CN, COOH, COOM, where M is a monovalent cation selected from the group consisting of Na, K, Rb, Cs, NH 4 , N(C 1 -C 10 -alkyl) 4 , N(C 1 -C 10 -alky/C 6 -C 10 -aryl) 4 , and SO 3 H, N-alkyl 2 -(C 1 -C 8 ), SO 2 -alkyl-(C 1 -C 6 ), SO-alkyl-(C 1 -C 6 ), NHCO-alkyl-(C 1 -C 4 ), COO-alkyl-(C 1 -C 8 ), CONH 2 , CO-alkyl-(C 1 -C 8 ), CO-phenyl, COO-phenyl, COO-aryl-(C 6 -C 10 ), CO-aryl-(C 6 -C 10 ), PO-phenyl 2 , POalkyl 2 -(C 1 -C 4 ), PO 3 H 2 , POalkyl-(C 1 -C 4 )(O-alkyl-(C 1 -C 6 )), PO(O-alkyl-(C 1 -C 6 )) 2 , Si(alkyl) 3 —(C 1 -C 8 ), where alkyl and aryl are as defined above.

Both R 1 and/or R 2 and also R 3 and R 4 may be linked by covalent bonds so as to form a five- to seven-membered ring. R 1 or R 2 may also be part of an organometallic compound, in particular part of a ferrocene-containing molecule.

As homogeneous metal atom-ligand complex, preference is given to using metal complexes having central atoms from the group consisting of Rh, Ru, Ir, Pd, Pt, Ni, in particular those which contain rhodium or iridium as central atom.

Preferred ligands are ligands of the formula (IV), among which further preference is given to those in which R 6 to R 9 are each, independently of one another, C 1 -C 8 -alkyl, C 5 -C 6 -cycloalkyl, C 6 -aryl, C 4 -C 5 -heteroaryl, where the number of heteroatoms is 1-2, selected from the group consisting of N, O, S, and the ring size is 5-6, or are naphthyl, with these groups being able to bear one or more substituents, preferably substituents selected independently from among hydrogen, C 1 -C 10 -alkyl, C 1 -C 6 -haloalkyl, C 5 -C 6 -cycloalkyl, C 2 -C 9 -heterocycloalkyl, C 6 -aryl, phenyl, C 4 -C 5 -heteroaryl, where the number of heteroatoms from the group consisting of N, O, S, can be 1-2, C 1 -C 6 -alkoxy, OCO-alkyl-(C 1 -C 6 ), O-aryl-C 6 , C 1 -C 6 -trihalomethylalkyl, fluoro, chloro, bromo, iodo, nitro, hydroxy, oxo, thio, thiolato, amino, C 1 -C 8 -substituted amino of the types mono-, di-, tri-C 1 -C 8 -alkylamino or C 2 -C 8 -alkenylamino or mono- and di-C 6 -C 8 -arylamino or C 1 -C 8 -alkyl-C 6 -C 8 -arylamino, NH—CO-alkyl-C 1 -C 8 , NHCO-aryl-C 6 -C 8 , C 1 -C 8 -acyloxy, carboxyl, carboxylato of the formula COOR 12 , sulfinato, sulfonato of the formula SO 3 R 12 , phosphonato of the formula PO 3 H 2 , PO 3 HR 12 , PO 3 R 12 2 , where R 12 can be either a monovalent or divalent cation (Li + , Na + , K + , Mg 2+ , Ca 2+ ), NH 4 + , N(C 1 -C 10 -alkyl) 4 + , N(C 1 -C 10 -alkyl/C 6 -C 10 -aryl) 4 + , C 1 -C 8 -alkyl or C 6 -aryl, and tri-C 1 -C 6 -alkylsilyl.

Preference is also given to ligands in which Y 1 and y 2 are each a direct phosphorus-carbon bond and in which Z comprises from one to four carbon atoms, particularly preferably two carbon atoms.

Particular preference is given to systems in which a seven-membered ring can be formed from Z, X 1 , X 2 , P 1 and P 2 together with a coordinated metal.

Z is preferably a C 1 -C 6 -alkyl or C 2 -C 6 -alkenyl group or is part of a C 3 -C 8 -cycloalkyl, C 5 -C 8 -cycloalkenyl, C 2 -C 9 -heterocycloalkyl, C 1 -C 9 -heterocycloalkenyl, C 6 -C 14 -aryl, phenyl, naphthyl, fluorenyl, C 2 -C 9 -heteroaryl group, where the number of heteroatoms from the group consisting of N, O, S can be 1-4,

where all these groups may be monosubstituted or polysubstituted as described above.

If Z is part of a cyclic structural element, three- to nine-membered ring systems are preferred. Particular preference is given to five- to seven-membered ring systems. The ring system may contain from one to four heteroatoms from the group consisting of N, O, S, preferably one or two. The nitrogen of the ring system can be present as NR 10 , NR 10 R 11+ , NR 10 H + , NC(O)R 10 . The ring systems can be monosubstituted or polysubstituted as indicated for R 6 to R 9 or directly by alkoxy, halo, nitro, hydroxy, oxo, thio, thiolato, amino, substituted amino, cyano, sulfonato, phosphonato, trialkylsilyl groups, where the substituents may also be bridged to one another.

Particularly preferred ring systems are phenyl, ferrocenyl, cyclopentyl, cyclohexyl, pyridyl, pyrrole, furyl, thiophene, tetrahydrofuran, tetrahydrothiophene, piperidyl, pyrrolidinyl, dioxolane or sulfolane rings which may each be unsubstituted or substituted as described above.

For the purposes of the present invention, metallocenes such as ferrocenes are formally included in the group of aromatics.

The ligand system used according to the invention preferably comprises, in R 6 -R 12 , independently of one another, alkyl, cycloalkyl or/and aryl which each contain from 1 to 20, in particular from 1 to 6, carbon atoms.

Examples of achiral or chiral ligands are compounds of the formulae VI, VII, VIII, IX, X and XI,

where R 6 to R 10 and R 13 , R 14 are each, independently of one another, hydrogen, (C 1 -C 24 )-alkyl, (C 6 -C 10 )-aryl, O—(C 1 -C 24 )-alkyl or O—(C 6 -C 10 )-aryl and R 6 and R 7 and/or R 8 and R 9 may also be linked by a covalent bond so as to form a cyclic compound having from four to eight atoms, and m is 0, 1 or 2, n is 1, 2, 3, 4, 5 or 6 and k is 0 or 1.

Z is as defined above.

For the purposes of the present invention, alkyl is an unbranched or branched aliphatic or cyclic hydrocarbon and aryl is an aromatic radical which may also be an aromatic containing at least one nitrogen or oxygen atom.

Ligands of the formulae (VI) to (XI) include, for example, ones in which R 6 to R 9 and R 13 , R 14 are selected independently from the group consisting of (C 3 -C 8 )-alkyl, (C 6 -C 10 )-aryl, O—(C 5 -C 8 )-alkyl, O—(C 6 -C 10 )-aryl, where alkyl is an unbranched or branched aliphatic or cyclic hydrocarbon and aryl is an aromatic radical, and m is from zero to two and n is from one to six. Both alkyl and aryl may bear substituents selected independently from among hydrogen, O-alkyl-(C 1 -C 8 ), O-phenyl, phenyl, aryl, fluorine, chlorine, OH, NO 2 , Si-alkyl 3 -(C 1 -C 4 ), CF 3 , CN, SO 3 H, N-alkyl 2 -(C 1 -C 4 ), CO-phenyl, COO-phenyl, COO-aryl-(C 6 -C 10 ), CO-aryl-(C 6 -C 10 ), PO-phenyl 2 , POalkyl 2 -(C 1 -C 4 ), PO(O-alkyl-(C 1 -C 6 )) 2 , Si(alkyl) 3 -(C 1 -C 8 ), where alkyl and aryl are as defined above.

In these ligands, R 6 and R 7 and/or R 8 and R 9 may also be linked by a covalent bond so as to form a cyclic compound having from five to seven atoms.

Typical representatives of the ligand systems used in the process of the invention are phosphine and diposphine ligands and modifications of this ligand type, for example dppb (1,4-bis(diphenylphosphino)butane), dcypb (1,4-bis(dicyclohexylphosphino)butane), bppm (2-diphenylphosphino-methyl-4-diphenylphosphino-1-tert-butoxycarbonylpyrrolidine), diop (2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane) (Kagan et al., J. Amer. Chem. Soc. (1972), 94, 6429), (2R,3R,5R,6R)-2,3-dimethoxy-2,3-dimethyl-5,6-bis(diphenylphosphinomethyl)-1,4-dioxane (Berens et al., J. Org. Chem. (1995), 60, 8204), TPPTS (tris-(3-sulfophenyl)phosphine trisodium salt) (Herrmann et al., Angew. Chem., Int. Ed. Engl. (1995), 34, 811), BINAS (2,2′-bis[[bis(3-sulfophenyl)phosphino]methyl]-4,4′,7,7′-tetrasulfo-1,1′-binaphthyl octasodium salt) (Herrmann et al., Inorg. Synth. (1998), 32, 8), diphosphinite ligands based on carbohydrates as described, for example, in DD 140036 and WO 95/18787 and related ligand systems such as dpoe (1,2-bis(diphenylphosphinoxy)ethane), bdpch ((1R,2R)-(trans)-1,2-bis-(diphenylphosphinoxy)cyclohexane) and aminophosphine phosphinites (Agbossou et al., Coordination Chemistry Rev. 1998, 178-180, 1615), e.g. the PROPRAHOS analog (2R)-1-[[(diphenyl-phosphino)(cyclopenthyl)amino]methyl]-2-diphenylphosphinoxy-3-(1-naph-thalenyloxy)propane (Krause et al., J. Mol. Catal. A: Chem. (1995), 104, 147) and aminophosphines, e.g. (4S)-2-(2-(diphenylphosphino)phenyl)-4-isopropyl-1,3-oxazoline (Koch G., Lloyd-Jones G. C., Loiseleur O., Pfaltz A., Pretot R., Schaffner S., Schnider P., von Matt P. Recl. Trav. Chim. Pays-Bas 1995, 114, 206-10).

The phosphorus-containing ligands can be prepared under conditions with which those skilled in the art are familiar (for example by methods as are described in Chemistry of Organophosphorus Compounds, Ed. F. R. Hartley, Serial Ed. S. Patai, Vol. 1, John Whiley, 1990). Some of the ligands and/or metal complexes are commercially available (for example from Aldrich or Strem/ABCR).

The catalytically active metal complexes can be synthesized by, for example, reacting the phosphorus-containing ligands in a known manner (EP-A-0158875; EP-A-0437690) with rhodium, iridium, ruthenium, palladium, platinum, cobalt or nickel complexes containing labile ligands (e.g. [Rh(COD) 2 ]BF 4 , [RuCl 2 (COD)] n , [Ir(COD)Cl] 2 ). Furthermore, all methods with which an organometallic chemist is familiar can be utilized for generating appropriate complexes.

The catalysts can be produced in situ from the metal precursor and the ligand, or they are used in isolated form.

The process of the invention is generally carried out at a temperature of −40-100° C., preferably at −20-60° C.

The initial hydrogen pressure in the process of the invention can be varied in a wide range from 0.1 bar to 300 bar. The process is preferably carried out at 1 bar-100 bar, particularly preferably from 20 to 60 bar.

It can be advantageous to carry out the process of the invention in the presence of additives.

Additives are acids such as p-toluenesulfonic acid, tetrafluoroboric acid, phosphoric acid, sulfuric acid or acetic acid, bases such as sodium hydroxide, potassium hydroxide, tertiary amines, proton sponges, cesium carbonate, acetate or sodium carbonate, salts such as halides of the alkali metals or ammonium halides, phase transfer catalysts, surfactants or cyclodextrins, which are employed in amounts of 0-100 mol % based on the amine (II) used.

Preferred solvents for the reductive amination are alcohols, in particular C 1 -C 6 -alkanols, particularly preferably methanol, ethanol, propanol, isopropanol, or else water and mixtures thereof. In the case of sparingly soluble substrates, solvent mixtures of alcohols and halogenated hydrocarbons and/or ethers, in particular cyclic ethers such as THF, and/or aromatic hydrocarbons such as toluene are also useful.

The process can also be carried out in a 2-phase system as described, for example, in DE 19737053.

The catalyst is usually used in amounts of from 0.001 to 5 mol %, preferably from 0.001 to 0.01 mol %, based on the carbonyl component of the formula (I).

The following examples illustrate the invention without restricting it to them.