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Site-Selective Copper-Catalyzed Azidation of Benzylic C-H Bonds.

ABSTRACT: 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.

SUBMITTER: Suh SE

PROVIDER: S-EPMC7405889 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Site-Selective Copper-Catalyzed Azidation of Benzylic C-H Bonds.

Suh Sung-Eun SE Chen Si-Jie SJ Mandal Mukunda M Guzei Ilia A IA Cramer Christopher J CJ Stahl Shannon S SS

Journal of the American Chemical Society 20200623 26

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<sup>II</sup>-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 ...[more]

PMID: 32539355

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