Open AccessRegioselective Alkylative Cross-Coupling of Remote Unactivated C(sp3)–H Bonds
Author(s) -
Scott M. Thullen,
Sean M. Treacy,
Tomislav Rovis
Publication year - 2019
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.9b07014
Subject(s) - chemistry , regioselectivity , selectivity , catalysis , alkylation , amide , hydrogen bond , alkyl , hydrogen atom , yield (engineering) , medicinal chemistry , surface modification , combinatorial chemistry , photochemistry , stereochemistry , organic chemistry , molecule , materials science , metallurgy
The functionalization of unactivated C( sp 3 )-H bonds poses a significant challenge due to their ubiquity and relative similarity in most organic frameworks. Herein, we describe the use of a combined photoredox and nickel catalytic system for the regioselective C( sp 3 )-C( sp 3 ) coupling of unactivated C( sp 3 )-H bonds and alkyl bromides. Positional selectivity is dictated by a 1,5-hydrogen atom transfer (HAT) reaction by a pendent amide. Interception of this radical by a Ni catalyst allows distal alkylation to occur in good yield and excellent selectivity.