Asymmetric Organocatalytic Benzylation of α,β-Unsaturated Aldehydes with Toluenes

The direct organocatalytic enantioselective benzylation by using toluenes and α,β-unsaturated aldehydes is presented. The reaction is catalyzed by tert-butyldimethylsilyl-protected diphenylprolinol in the presence of a mild organic base and proceeds with excellent yields and enantioselectivities up to >99 % ee. This reactivity is based on a synergistic effect between the iminium ion intermediate and the base-activated toluene. Toluene derivatives having various electron-withdrawing substituents were also applied in this unprecedented transformation. The synthetic potential is demonstrated by manipulations of the products to, for example, biologically active phenylbenzazepines.