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The synthesis and characterization of a new series of aryl-and cycloalkyl-substituted aminophosphine phosphinites (1-8) obtained from the reaction of the three precursors (S)-2-hydroxymethyl azetidine, (S)-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline, and (S)-2hydroxymethylindoline and chlorophosphines is described. The aromatic ring in (S)-2hydroxymethylindoline has allowed the synthesis and isolation of tricarbonyl chromium complexed amino alcohols syn-10 and anti-10, which were similarly converted into the corresponding aminophosphine phosphinites 11-13, presenting a stereogenic center and a planar chirality. Ligand 5 ((S)-Cp,Cp-IndoNOP) revealed an unprecedented 31 P NMR fluxional behavior related to a rotation inhibition around the P-heteroatom (N and O) bonds. These new AMPP ligands were used in the enantioselective hydrogenation of various R-functionalized ketones, i.e., dihydro-4,4-dimethyl-2,3-furandione 14, N-benzyl benzoylformamide 15, ethylpyruvate 16, and 2-(N,N-dimethyl)aminoacetophenone hydrochloride 17. The stereoelectronic effects generated by the presence of the tricarbonyl chromium moiety onto the hydrogenations have been assessed. The beneficial effect of the matching chiralities in ligand syn-12 associated with the use of the most appropriate nonchiral ligand Cl has resulted in a win of 13% of ee for the rhodium-based hydrogenation of 15. While using the most suitable new chiral AMPP ligand from this study, the four above-mentioned substrates were converted into the corresponding optically active alcohols in >99% ee (l4/5), >99% ee (15/6), 87% ee (16/5), and >99% ee (17/5), respectively.

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The chiral new aminophosphine-phosphinites (AMPP's 1-7) have been synthesised and applied successfully in the enantioselective hydrogenation of dihydro-4,4-dimethyl-2,3-furandione 8, Nbenzylbenzoylformamide 9, and ethylpyruvate 10 providing the hydroxy products in up to 97, 95, and 80% ee, respectively.Transition metal catalysed enantioselective hydrogenation of ketones provides efficient ways to enantiopure hydroxy substituted building blocks for organic synthesis. For that purpose, the use of rhodium and ruthenium catalysts modified by chiral diphosphines has been the most successful. Up to date, an abundance of chiral bisphosphines have been developed for their application in the asymmetric hydrogenation of enamides, ketones and imines. 1 Interestingly, even though particularly efficient ligands have been reported, the design of new ligands has been continuously attracting research interest for more than two decades. 2 In fact, from a practical viewpoint, it is still of strong current interest to develop highly effective diphosphines ligands. 3Our interest in the synthesis of chiral diphosphines employing naturalproduct based precursors, i.e. aminoalcohols and their derivatives both easily accessible from the chiral pool, has allowed a convenient access to a large number of aminophosphine-phosphinite type ligands. The latter have been used with success in various asymmetric reactions. 4 A very successful application of such ligands is the asymmetric hydrogenation of functionalized ketones. 5 As a result of our observations, we concluded that two important points have to be fulfilled in order to obtain highly efficient AMPP ligands for the hydrogenation of carbonyl functions. Firstly, the presence of cycloalkyl substituents on the phosphorus atoms of the diphosphine increases both the rates and selectivities of the reaction. Secondly, the structure of the chiral backbone has to provide limited flexibility and beneficial steric factors allowing consequently increased enantioselectivities. This fact has already been proven by previous experimental results. 5,6 On the other hand, some of us have an ongoing interest in the synthesis of chiral aminoalcohol ligands derived from α-aminoacids and their application in asymmetric reactions such as the enantioselective addition of diethyl zinc to aldehydes 7 and the enantioselective reduction of prochiral ketones with BH 3 ·THF. 8 As a consequence, several "natural" and "artificial" auxiliaries presenting various steric and substitution patterns have been prepared and were tested for their catalytic and inductive abilities in the above reactions. As some of them seem to be particularly well suited for a transformation into diphosphines, we thought to use them in order to probe the above hypothesis. In this paper, we report the synthesis of the resulting new aminophosphine-phosphinites and their application in asymmetric hydrogenation of ketones.The three β-aminoalcohol precursors used in this study i.e. (S)-1-pyrrolidin-2-ylcyclopentanol, 9 (S)-2-hydroxymethyl azetidine, ...

1999 stereochemistry stereochemistry (general, optical resolution) O 0030 04 -041 Enantioselective Hydrogenation of Functionalized Ketones. Synthesis and Application of New Chiral Aminophosphine-Phosphinite Ligands. -New chiral aminophosphine-phosphinites such as (I) are easily obtained by coupling of chiral amino alcohols with chlorophosphines. They are successfully applied to enantioselective hydrogenation of derivatives of α-ketocarboxylic acids. -(PASQUIER, C.; EILERS, J.; REINERS, I.; MARTENS, J.; MORTREUX, A.; AGBOSSOU, F.; Synlett (1998) 10, 1162-1164; Lab. Catal.