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

Sung Eun Suh, Si Jie Chen, Mukunda Mandal, Ilia A. Guzei, Christopher J. Cramer, Shannon S. Stahl

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 CuII-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.

Original languageEnglish (US)
Pages (from-to)11388-11393
Number of pages6
JournalJournal of the American Chemical Society
Volume142
Issue number26
DOIs
StatePublished - Jul 1 2020

Bibliographical note

Funding Information:
This work was supported by funding from the NIH (R01 GM126832 and R35 GM134929). Spectroscopic instrumentation was supported by a gift from Paul J. Bender, the NSF (CHE-1048642), and the NIH (1S10 OD020022-1). M.M. acknowledges a doctoral dissertation fellowship from the University of Minnesota. The authors thank Dr. Joshua A. Buss for providing a sample of Gomberg’s dimer and Amelia M. Wheaton for assistance with X-ray crystallography.

Publisher Copyright:
© 2020 American Chemical Society.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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