Nickel-Catalyzed Dearomative Arylboration of Indoles: Regioselective Synthesis of C2-and C3-Borylated Indolines

Indole dearomatization is an important strategy to access indolines: a motif present in a variety of natural products and biologically active molecules. Herein, a method for transition-metal catalyzed regioselective dearomative arylboration of indoles to generate diverse indolines is presented. The method accomplishes intermolecular dearomatization of simple indoles through a migratory insertion pathway on substrates that lack activating or directing groups on the C2- or C3-positions. Synthetically useful C2- and C3-borylated indolines can be accessed through a simple change in N-protecting group in high regio- and diastereoselectivities (up to >40:1 rr and >40:1 dr) from readily available starting materials. Additionally, the origin of regioselectivity was explored experimentally and computationally to uncover the remarkable interplay between carbonyl orientation of the N-protecting group on indole, electronics of the C2-C3 pi-bond, and sterics. The method enabled the first enantioselective synthesis of (-)-azamedicarpin.

Automated summary

The study introduces a novel method for regioselective dearomatization of indoles catalyzed by transition metals, leading to diverse indolines. By changing the N-protecting group, C2- and C3-borylated indolines can be efficiently accessed with high regio- and diastereoselectivities.