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.