Open AccessCopper-Catalyzed Cross-Coupling of Benzylic C–H Bonds and Azoles with Controlled N-Site Selectivity
Author(s) -
Si Jie Chen,
Dung L. Golden,
Shane W. Krska,
Shan S. Stahl
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.1c07117
Subject(s) - chemistry , selectivity , catalysis , combinatorial chemistry , copper , molecule , coupling (piping) , stereochemistry , medicinal chemistry , computational chemistry , organic chemistry , mechanical engineering , engineering
Azoles are important motifs in medicinal chemistry, and elaboration of their structures via direct N-H/C-H coupling could have broad utility in drug discovery. The ambident reactivity of many azoles, however, presents significant selectivity challenges. Here, we report a copper-catalyzed method that achieves site-selective cross-coupling of pyrazoles and other N-H heterocycles with substrates bearing (hetero)benzylic C-H bonds. Excellent N -site selectivity is achieved, with the preferred site controlled by the identity of co-catalytic additives. This cross-coupling strategy features broad scope for both the N-H heterocycle and benzylic C-H coupling partners, enabling application of this method to complex molecule synthesis and medicinal chemistry.