Copper catalyzed benzylic sp3 C-H alkenylation

Ting-An Chen; Richard J Staples; Timothy H Warren

doi:10.1039/d4sc03430a

Copper catalyzed benzylic sp³ C-H alkenylation

Chem Sci. 2024 Sep 19;15(42):17685-17690. doi: 10.1039/d4sc03430a. Online ahead of print.

Authors

Ting-An Chen^{1

2}, Richard J Staples², Timothy H Warren²

Affiliations

¹ Department of Chemistry, Georgetown University Washington D.C. 20057 USA.
² Department of Chemistry, Michigan State University East Lansing Michigan 48824 USA [email protected].

Abstract

The prenyl group is present in numerous biologically active small molecule drugs and natural products. We introduce benzylic C-H alkenylation of substrates Ar-CH₃ with alkenylboronic esters (CH₂)₃O₂B-CH[double bond, length as m-dash]CMe₂ as a pathway to form prenyl functionalized arenes Ar-CH₂CH[double bond, length as m-dash]CMe₂. Mechanistic studies of this radical relay catalytic protocol reveal diverse reactivity pathways exhibited by the copper(ii) alkenyl intermediate [Cu^II]-CH[double bond, length as m-dash]CMe₂ that involve radical capture, bimolecular C-C bond formation, and hydrogen atom transfer (HAT).