New Strategic Reactions for Organic Synthesis: Catalytic Asymmetric C−H Activation α to Nitrogen as a Surrogate for the Mannich Reaction

The C−H activation of silyl ethers by means of rhodium carbenoid-induced C−H insertion represents a very direct method for the stereoselective synthesis of silyl-protected β-hydroxy esters. The reaction can proceed with very high regio-, diastereo-, and enantioselectivity and represents a surrogate to the aldol reaction. The reaction is catalyzed by the rhodium prolinate complex Rh2(S-DOSP)4. A critical requirement for the high chemoselectivity is the use of donor/acceptor-substituted carbenoids such as those derived from methyl aryldiazoacetates. A range of silyl ethers may be used such as allyl silyl ethers, tetraalkoxysilanes, and even simple trimethylsilyl alkyl ethers. In general, C−H activation preferentially occurs at methylene sites, as the reactivity is controlled by a delicate balance between steric and electronic effects.