Studies On The Asymmetric Cyanosilylation Of Aldehydes

A series of chiral ligands derived from Ramipril and amines were synthesized. The complexes prepared from these ligands and Ti(OiPr)4 were applied to catalyze asymmetric addition of trimethylsilylcyanide to aldehydes.First, with benzaldehyde as a standard substrate, several factors which affected the enatioselectivity of the reaction were investigated in detail, such as the structure of the ligands, central metal reagents, molar ratio of chiral ligands to Ti(OiPr)4, solvent, concentration of substrate, additives, the amount of additive, amount of catalyst, reaction temperature and so on. Then under the optimized conditions: -78 oC, concentration of benzaldehyde 0.2 M in CH2Cl2, 5 mol% 64h-Ti(OiPr)4 (2:1), in the presence of 20 mol% 4-methylbenzoic acid, benzaldehyde was converted to the corresponding product, 2-hydroxy-2-phenylacetonitrile with 99% yield and 80% ee.Subsequently, a range of aromatic, aliphatic, heterocylic andα,β-unsturated aldehydes were investigated under the optimized conditions. The corresponding products were obtained in 83-99% yields and 45-80% ee.Based on the experiment results, the catalyst cycle was proposed as a pathway in which Lewis acid and Lewis base activated aldehyde and trimethylsilylcyanide, respectively.