Stereoselective C-O silylation and stannylation of alkenyl acetates

Carbon-heteroatom bond formation reactions are of high interest in synthetic organic chemistry. Here, the authors report the cobalt-catalyzed synthesis of tri- and tetrasubstituted alkenyl silanes and stannanes via C-O functionalization of vinyl acetates using silylzinc pivalate and stannylzinc chloride as the nucleophiles. Facile formation of carbon-heteroatom bonds is a long-standing objective in synthetic organic chemistry. However, direct cross-coupling with readily accessible alkenyl acetates via inert C-O bond-cleavage for the carbon-heteroatom bond construction remains challenging. Here we report a practical preparation of stereoselective tri- and tetrasubstituted alkenyl silanes and stannanes by performing cobalt-catalyzed C-O silylation and stannylation of alkenyl acetates using silylzinc pivalate and stannylzinc chloride as the nucleophiles. This protocol features a complete control of chemoselectivity, stereoselectivity, as well as excellent functional group compatibility. The resulting alkenyl silanes and stannanes show high reactivities in arylation and alkenylation by Hiyama and Stille reactions. The synthetic utility is further illustrated by the facile late-stage modifications of natural products and drug-like molecules. Mechanistic studies suggest that the reaction might involve 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.

Automated summary

The authors present a cobalt-catalyzed synthesis of tri- and tetrasubstituted alkenyl silanes and stannanes via C-O functionalization of vinyl acetates using silylzinc pivalate and stannylzinc chloride as nucleophiles. This reaction is challenging but has significant importance in synthetic organic chemistry.