132. New Strategic Reactions for Organic Synthesis:  Catalytic Asymmetric C−H Activation α to Oxygen as a Surrogate to the Aldol Reaction

Authors: Huw M. L. Davies , Rohan E. J. Beckwith , Evan G. Antoulinakis , and Qihui Jin

J. Org. Chem.,

2003, 68 (16), 6126–6132


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.

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