Studies On The Cyanosilylation Of Carbonyl Compounds

Nine hydrogenated chiral Schiff bases derived from (1R, 2S)-l,2-diphenyl-2-aminoethanol and 2-hydroxybenzaldehyde with different substituents were synthesized, as well as four other hydrogenated chiral Schiff bases with only one chiral carbon center and one hydrogenated chiral Salen ligand. The complexes prepared in situ from these ligands and Ti(O-iPr)4 were then applied to the asymmetric addition of trimethylsilylcyanide to aldehydes.First, with benzaldehyde as a test substrate, we investigated several factors in detail that affect the enatioselectivity, such as the structure of the ligands(steric and electric effects); central metal; molar ratio of chiral ligands to Ti(O-iPr)4; solvent; concentration of substrates; different amount of catalyst; reaction temperature and so on. Then we got the optimized reaction conditions: -20C, concentration of benzaldehyde = 0.5M in CH2Cl2, 5 mol% (1R, 25)-l,2-diphenyl-2-(N-2'-hydroxy-3'-methyl-benzyl)aminoethanol(57b) -Ti(O-iPr)4 (1:1) (in situ). Under these optimal conditions, benzaldehyde was converted to the corresponding product, 2-hydroxy-2-phenylacetonitrile with 92% ee.Then, 18 different aromatic, aliphatic, heterocylic aldehydes were studied under the optimal conditions. The corresponding products were obtained in90-99% yields and 57-93% ee.At last, the author discussed the different results between hydrogenated chiral Schiff bases catalytic system and chiral Schiff bases reported by Oguni, and suggested the possible reasons for the virtues of this catalytic system.In addition, the use of phenolic N-oxide as a catalyst for cyanosilylation of ketones was found to be a convenient and high effective method for praperation of racemic cyanohydrins. The phenolic N-oxide (down to 5 mol%) was used to afford racemic cyanohydrins with excellent isolated yields (up to 99%). This approach covers the substrate range of aliphatic, aromatic, heterocyclic and steric hindrance ketones. The low catalyst loading, high concentration, metal-free, room temperature, short reaction time, mild conditions and the good generality of substrates all make this protocol practical.