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

Abstract

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 π-bond, and sterics. The method enabled the first enantioselective synthesis of (−)-azamedicarpin.

Pd(ii)/Lewis acid catalyzed regioselective olefination of indole with dioxygen

“…20–22 Over the past years, modifications and fabrications of the indole unit have aroused great interest in organic synthesis, especially for the direct C–H regioselective functionalization of the indole ring which can construct versatile unique heterocyclic frameworks. 23–27 Among the existing indole skeletons in nature, 3-vinylindoles have attracted much attention from both industrial and academic communities because of their biological and pharmaceutical value and because they can be easily obtained through the direct olefination of indoles at the C-3 position. To date, versatile protocols have been explored for the syntheses of 3-vinylindole and its derivatives through olefination.…”

Cooperative Pd/Cu Catalysis for Alkene Arylboration: Opportunities for Divergent Reactivity

“…While reactions of unactivated alkenes are particularly challenging, Semba et al have made a notable advance (Scheme H) . While not highlighted in this review, recent developments in Ni catalysis have led to the development of a general process for 1,2-arylboration of unactivated alkenes. , …”

Recent Advances in Non-Precious Metal Catalysis

“…The synthetic application of this methodology was demonstrated by two-step access to the key substituted indanol intermediate previously applied 13 in the synthesis of quebrachamine (Scheme 8). 17 This methodology provides access to substituted indoles with excellent control of the regioselectivity and diastereoselectivity for the formation of C(2) or C(3) borylated indolines. The nature of the N-protecting group plays an important role in controlling the regioselectivity.…”