Mechanism of the α,α-diarylprolinol trimethylsilyl ether-catalyzed enantioselective C-C, C-N, C-F, C-S, and C-Br bond forming reactions

Theoretical calculations were employed to investigate the enantioselectivity of the alpha,alpha-diarylprolinol trimethylsilyl ether-catalyzed alpha-functionalization of aldehydes with various different electrophiles, via an enol intermediate. The reactions investigated were (i) Michael-aldol condensation, (ii) Michael addition, (iii) Mannich reaction, (iv) alpha-amination of an aldehyde, (v) alpha-fluorination of an aldehyde, (vi) alpha-sulfenylation of an aldehyde, and (vii) alpha-bromination of an aldehyde. In all seven cases, our proposed enol mechanism is able to account for the experimentally observed enantioselectivity of the products. Our calculations strongly suggest that these catalyzed reactions proceed via an enol intermediate and not via an enamine intermediate. (C) 2009 Elsevier Ltd. All rights reserved.