Gold-Catalyzed Cascade Cyclization Of Indolyl Homopropargyl Amides:Stereospecific Construction Of Bridged Aza-[n.2.1] Skeletons

Gold-catalyzed nucleophilic addition reactions to alkynes have received tremendous interest since the last decade and been widely used in the facile synthesis of an incredible variety of complex molecules,especially the valuable cyclic compounds.Among these,the terminal alkynes can undergo various highly regioselective transformations catalyzed by gold,thus providing an efficient way for C-C,C-H and C-X bond formation.However,Markovnikov regioselectivity is normally observed in this kind of nucleophilic addition.Here we report an efficient gold-catalyzed anti-Markovnikov cycloisomerization-initiated tandem reaction of indolyl homopropargyl amides,where gold catalyzes both the hydroamination and Friedel-Crafts alkylation process.This method delivers valuable bridged aza-[n.2.1]skeletons with wide substrate scope,and high diastereoselectivity and enantioselectivity by a chirality-transfer strategy.Moreover,a mechanistic rationale for this novel cascade cyclization is supported by both control experiments and theoretical calculations.