Catalytic Net Oxidative C-C Activation and Silylation of Cyclopropanols with a Traceless Acetal Directing Group

Redox-neutral carbon-carbon (C-C) bond activation and functionalization strategies of cyclopropanols that give metallo homoenolate have offered merits to construct a range of useful beta-functionalized ketones in an inverse-polarity fashion. Discovery and identification of oxidative C-C activation reactions of cyclopropanols that generate metallo enolate-homoenolate would provide an opportunity to afford alpha,beta-difunctionalized ketones. We report catalytic, net oxidative C-C activation, and silylation of cyclopropanols with traceless acetal directing groups under consecutive Ir and Rh catalysis in regio-, stereo-, and chemo-selective fashion. In detail, Ir-catalyzed hydrosilylation of cyclopropyl acetates provides the acetal directing group in quantitative yield. Rh-catalyzed proximal C-C silylation of the resulting cyclopropyl silyl acetal produces the metallo enolate-homoenolate equivalent, dioxasilepine, which uniquely holds an interconnected beta-silyl moiety and Z-vinyl acetal. Upon sequential treatment of a silaphile that removes the acetal directing group and electrophile, the seven-membered silicon-containing heterocycle, serving as the ketone alpha,beta-dianion equivalent, delivers alpha,beta-difunctionalized ketones. Scope of the hitherto unexplored reactivity of cyclopropanols toward net oxidative C-C silylation and the versatility of the resulting dioxasilepines were demonstrated. These include late-stage, net oxidative C-C silylation of biologically relevant molecules and facile production of a range of alpha,beta-difunctionalized ketones. Preliminary mechanistic studies suggest that the C-C activation harnessing the electron-rich Wilkinson-type catalyst is likely the turnover-determining step and a Rh-pi interaction is the key to the efficient metal insertion to the proximal C-C bond in cyclopropanols.

Automated summary

In this study, a method for oxidative C-C activation and silylation of cyclopropanols was reported. By consecutive iridium and rhodium catalysis, α,β-difunctionalized ketones were synthesized with high selectivity.