Open AccessNickel-Catalyzed Dearomative Arylboration of Indoles: Regioselective Synthesis of C2- and C3-Borylated Indolines
Author(s) -
Grace L. Trammel,
Rositha Kuniyil,
Phillip F. Crook,
Peng Liu,
M. Kevin Brown
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c05902
Subject(s) - regioselectivity , chemistry , indole test , combinatorial chemistry , steric effects , intermolecular force , catalysis , functional group , molecule , stereochemistry , organic chemistry , polymer
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.