Increasing enantioselectivities and reactivities by stereochemical tuning:Fenchone-based catalysts in dialkylzinc additions to benzaldehyde

Trimethylsilyl substitutions of the fenchyl alcohols [(1R,2R,4S)-exo-(2-Ar) -1,3,3-trimethylbicyclo]heptan-2-ol, Ar = 2-methoxyphenyl (1) and Ar = 2-(d imethylaminomethyl)phenyl(2)1 yield the chiral ligands 3 [Ar = 2-methoxy-3- (trimethylsilyl)phenyl] and 4 [Ar = 2- (dimethylaminomethyl) 3-(trimethylsi lyl)phenyl]. Increased reactivities and enantioselectivities in diethylzinc additions to benzaldehyde are obtained from 3 (63% ee R) and 4 (93% ee S), relative to 1 (26% ee S) and 2 (73% ee S). X-ray crystal structures of 3 a nd of its methylzinc complex 3-Zn reveal out-of-plane bending of the methox y groups as major geometrical consequences of the trimethylsilyl substituti ons. Analyses of QM/MM ONIOM mu-O transition-structure models for 1, 2, 3, and 4 show that trimethylsilyl-induced distortions of methoxy and of dimeth ylaminomethyl groups explain the observed increased enantioselectivities.