Enantioselective copper-catalyzed dearomative borylative cyclization of indoles and mechanistic insights

Abstract

Alicyclic nitrogen heterocycles, such as enantioenriched polycyclic fused [1,2-a]indoline derivatives, are widespread in natural products, agrochemicals and pharmaceutical agents. Existing methods predominantly rely on the recent emerging Heck-type catalytic asymmetric dearomatization (CADA) protocol, wherein noble palladium catalysts commonly necessitate the form aryl-Pd species-triggered these transformations. In contrast, a more sustainable base metal catalysis paradigm through alkyl metal species disrupting the aromaticity, that is, the utilization of challenging asymmetric Csp³–Csp³ bond formation entry to such important chiral densely functionalized polycyclic molecular scaffolds, remains an elusive task. Herein, we report the first copper-catalyzed dearomative borylative cyclization of indoles under mild reaction conditions, affording an array of valuable Bpin-containing pyrrolo-fused [1,2-a]indolines bearing four consecutive stereogenic centers with excellent enantio- and diastereoselectivity. The synthetic potential was documented via an array of useful transformations. Density functional theory (DFT) calculation studies elucidated the origin of the chemo-, regio-, enantio- and diastereoselectivities of this conversion.