Stereoselective C–O Silylation and Stannylation

Abstract On the basis of umpolung strategy, a practical preparation of stereoselective tri- and tetrasubstituted alkenyl silanes and stannanes by performing cobalt-catalyzed cross-coupling between readily available alkenyl acetates and solid Me2PhSi‒ZnOPiv•Li2(Cl)(OPiv), as well as (nBu)3Sn‒ZnCl•LiCl under remarkably mild reaction conditions has been developed. In this reaction, direct C‒O bond silylation and stannylation character by their complete control of chemoselectivity, stereoselectivity, as well as excellent functional group compatibility, thus providing an expedient route to prepare tri- and tetrasubstituted alkenyl silanes and stannanes. The resulting polysubstituted alkenyl silanes and stannanes show high reactivity in arylation and alkenylation by Hiyama and Stille reactions. The synthetic utility of our protocol was further illustrated by the facile late-stage modifications of natural products and druglike molecules. Detailed mechanistic studies suggest that the reaction involves a chelation-assisted oxidative insertion of cobalt species to C‒O bond. We anticipate that our findings should prove instrumental for potential applications of this technology to organic syntheses and drug discoveries in medicinal chemistry.