Catalytic Asymmetric N-Alkylation of Indoles and Carbazoles through 1,6-Conjugate Addition of Aza-para-quinone Methides.

Abstract

Catalytic asymmetric N-alkylation of indoles and carbazoles represents a family of important but underdeveloped reactions. Herein, we describe a new organocatalytic strategy in which in situ generated aza-para-quinone methides are employed as the alkylating reagent. With the proper choice of a chiral phosphoric acid and an N-protective group, the intermolecular C-N bond formation with various indole and carbazole nucleophiles proceeded efficiently under mild conditions with excellent enantioselectivity and functional-group compatibility. Control experiments and kinetic studies provided important insight into the reaction mechanism.