Studies On The Asymmetric Cyanosilylation Of Aldehyde

Seventeen chiral aza ligands derived from different readily available amino acids, diamines and amino alcohols were synthesized. The complexes prepared in situ from these ligands and Ti(O-iPr)₄ were applied to catalyze asymmetric addition of trimethylsilylcyanide to aldehydes.First, with benzaldehyde as a standard substrate, we investigated several factors in detail that affect the enatioselectivity of the reaction, such as the structure of the ligands, central metal, molar ratio of chiral ligands to Ti(O-iPr)₄, solvent, concentration of substrates, additive, the amount of additive, different amount of catalyst, reaction temperature and so on. Then we got the optimized reaction conditions: 0 ℃, concentration of benzaldehyde = 0.25M in CH₂Cl₂, 15 mol% 83d - Ti(O-iPr)₄ (1:2) (in situ), in the presence of p-nitrobenzic acid (the molar ratio of additive to 83d is 1:2 ). Under the optimal conditions, benzaldehyde was converted to the corresponding product, 2-hydroxy-2-phenylacetonitrile with 88% ee.Then, the asymmetric addition of trimethylsilyl cyanide to a range of different aromatic, aliphatic, heterocylic aldehydes were investigated under the optimal conditions. The corresponding products were obtained in 24-98% yields and 17-92% ee.