The use of chiral (salen)TiCl2 complexes to induce the asymmetric addition of trimethylsilyl cyanide to aldehydes has been investigated. The complexes are catalytically active at substrate-to-catalyst ratios as high as 1000:1, and the optimal catalyst (2e) which is derived from (R,R)-1,2-diaminocyclohexane and 3,5-di-tert-butyl-2-hydroxybenzaldehyde produces trimethylsilyl ethers of cyanohydrins with up to 90% enantiomeric excess at ambient temperature. Water plays a key role in these reactions since under strictly anhydrous conditions much lower enantiomeric excesses are produced. The role of water has been shown to be to generate dimeric complexes of the form [(salen)Ti(μ-O)]2 (4) which are the real catalyst precursors. A structure for one of these complexes (4a derived from (R,R)-1,2-diaminocyclohexane and 2-hydroxybenzaldehyde) has been determined by X-ray crystallography. The dimeric complexes are more active than the dichloride precursors, and at substrate-to-catalyst ratios between 100 and 1000:1 give cyanohydrin trimethylsilyl ethers with up to 92% enantiomeric excess in less than 1 h at ambient temperature.

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A longstanding problem in enantioselective catalysis concerns the transformation of prochiral ketones into chiral amines. To date, this reaction is mainly associated with the hydrogenation of imines or enamine derivatives using late transition metal complexes based on chiral P-ligands. However, the one-pot reduction of a suitable intermediate arising from the reaction of the carbonyl compounds and amine would be much more favorable (direct reductive amination), since one step is saved. In this account, we report on the story of the development of chiral Rh-diphosphine catalysts, which can be used for this enantioselective transformation. For example, a-amino acids were prepared by this methodology in up to 98% ee. Before we achieved this goal, all possible products arising from the reaction between carbonyl component and starting amine, like imines, enamines and N,O-acetals, and serving therefore as potential substrates, were successfully subjected to hydrogenation. Apparently, in the direct reductive amination, different substrates may serve as precursors for chiral amine products depending on the starting material and reaction conditions. This matter complicates the rational design of catalysts. Therefore, the use of high-throughput methods for identification of efficient catalysts is recommended.

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