Rhodium-Catalyzed Enantio- and Diastereoselective Synthesis of Allenyl Alcohols via Three-Component Dicarbofunctionalization of 1,3-Enynes

Multicomponent reactions have the advantage of high step-economy with the formation of multiple bonds in a controlled manner in a single operation. Nevertheless, asymmetric C–H bond activation that enables three-component coupling remains largely underexplored. Reported herein is rhodium-catalyzed C–H bond activation of indoles and sequential addition to 1,3-enyne and an activated aldehyde, allowing facile synthesis of chiral allenyl alcohols in high regio-, enantio-, and diastereoselectivity under mild reaction conditions. Mechanistic studies suggested the involvement of C–H bond activation and olefin insertion that gives a rhodium(III) propargyl intermediate, and the interaction between the propargyl and the aldehyde is both enantio- and diastereo-determining. In particular, a silver additive serves to enhance the diastereoselectivity.