Open AccessSite-Selective Copper-Catalyzed Azidation of Benzylic C–H Bonds
Author(s) -
Sung-Eun Suh,
Si Jie Chen,
Mukunda Mandal,
Ilia A. Guzei,
Christopher J. Cramer,
Shan S. Stahl
Publication year - 2020
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.0c05362
Subject(s) - chemistry , azide , selectivity , tetrazole , amine gas treating , combinatorial chemistry , catalysis , copper , molecule , pyrrole , surface modification , density functional theory , organic chemistry , computational chemistry
Site selectivity represents a key challenge for non-directed C-H functionalization, even when the C-H bond is intrinsically reactive. Here, we report a copper-catalyzed method for benzylic C-H azidation of diverse molecules. Experimental and density functional theory studies suggest the benzyl radical reacts with a Cu II -azide species via a radical-polar crossover pathway. Comparison of this method with other C-H azidation methods highlights its unique site selectivity, and conversions of the benzyl azide products into amine, triazole, tetrazole, and pyrrole functional groups highlight the broad utility of this method for target molecule synthesis and medicinal chemistry.