Enhancement of the Catalytic Activity of Chiral H 8 ‐BINOL Titanium Complexes by Introduction of Sterically Demanding Groups at the 3‐Position

The activity of chiral titanium catalysts derived from H 8 ‐BINOL ligands in the enantioselective arylation of an aldehyde with PhTi(O i Pr) 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‐H 8 ‐BINOL (DTBP=3,5‐di‐ tert ‐butylphenyl) and DAP‐H 8 ‐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(O i Pr) 3 units in a DPP‐H 8 ‐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 H 8 ‐BINOL catalyst system.