Enhancement of the Catalytic Activity of Chiral H8 -BINOL Titanium Complexes by Introduction of Sterically Demanding Groups at the 3-Position.

Abstract

The activity of chiral titanium catalysts derived from H8 -BINOL ligands in the enantioselective arylation of an aldehyde with PhTi(OiPr)3 is significantly enhanced by an increase of the size of the substituent at the 3-position. High enantioselectivity (> 90 % ee) can be obtained even at a substrate/catalyst ratio (S/C) of 800 for DTBP-H8 -BINOL (DTBP=3,5-di-tert-butylphenyl) and DAP-H8 -BINOL (DAP=3,5-di(9-anthraceny)phenyl). These titanium catalysts are successfully applied to the enantioselective arylation and heteroarylation of aldehydes at a S/C ratio of 400 by using organotitanium reagents generated in situ from bromide precursors. The remarkable weakening of the intramolecular aggregation of the two -Ti(OiPr)3 units in a DPP-H8 -BINOL (DPP=3,5-diphenylpheny)-derived bis-titanium complex is revealed by X-ray and variable-temperature (VT)-NMR studies. Based on these observations, a catalytic cycle, involving the rate-limiting aryl group transfer followed by aldehyde complexation and enantioselective arylation, is proposed to account for the high activity of the 3-substituted H8 -BINOL catalyst system.