Structure/Enantioselectivity Study of the Asymmetric Addition of Trimethylsilylcyanide to Benzaldehyde Catalyzed by Ti(IV)−Schiff Base Complexes

Abstract

In the presence of titanium tetraisopropoxide, tridentate salen ligands derived from cis-1-amino-2-indanol have been utilized in the asymmetric addition of trimethylsilylcyanide to benzaldehyde, which gave the cyanohydrins in up to 85% ee. We have examined the reaction of titanium tetraisopropoxide with these salen ligands by NMR spectrometry and X-ray crystallography. Reaction of ligands derived from salicylaldehydes with bulky substituents in the 3-position with titanium tetraisopropoxide gave the L*Ti(O-i-Pr)2 complexes, which are the proposed precatalysts in the asymmetric addition reaction. These ligands give good to very good enantioselectivity in the asymmetric trimethylsilylcyanation reaction. However, with groups smaller than tert-butyl in the 3-position, substantial amounts (up to 73%) of the catalytically inactive L2*Ti species are formed, resulting in large drops in the ee's of the cyanohydrins. The L2*Ti species were formed as mixtures of diastereomers, one of which has been characterized by X-ray crystallography. The crystal structure shows the titanium to be bonded to two ligands with a pseudo-octahedral coordination geometry. The ligands are bound in a meridional fashion and the complex is C2-symmetric. Use of 2 equiv of ligand relative to titanium tetraisopropoxide resulted in significant reductions in the ee of the cyanohydrin product, presumably due to formation of increased amounts of the inactive diastereomeric L2*Ti complexes.