Rhodium-Catalyzed Enantioselective Formal [4+1] Cyclization of Benzyl Alcohols and Benzaldimines: Facile Access to Silicon-Stereogenic Heterocycles

The carbon-to-silicon switch in formation of bioactive sila-heterocycles with a silicon-stereogenic center has garnered significant interest in drug discovery. However, metal-catalyzed synthesis of such scaffolds is still in its infancy. Herein, a rhodium-catalyzed enantioselective formal [4+1] cyclization of benzyl alcohols and benzaldimines has been realized by enantioselective difunctionalization of a secondary silane reagent, affording chiral-at-silicon cyclic silyl ethers and sila-isoindolines, respectively. Mechanistic studies reveal a dual role of the rhodium-hydride catalyst. The coupling system proceeds via rhodium-catalyzed enantio-determining dehydrogenative OH silylation of the benzyl alcohol or hydrosilylation of the imine to give an enantioenriched silyl ether or silazane intermediate, respectively. The same rhodium catalyst also enables subsequent intramolecular cyclative C−H silylation directed by the pendent Si-H group. Experimental and DFT studies have been conducted to explore the mechanism of the OH bond silylation of benzyl alcohol, where the Si-O reductive elimination from a Rh(III) hydride intermediate has been established as the enantiodetermining step.