Pd(II)-Catalyzed Synthesis of Benzocyclobutenes by β-Methylene-Selective C(sp3)-H Arylation with a Transient Directing Group

Philip A Provencher; John F Hoskin; Jonathan J Wong; Xiangyang Chen; Jin-Quan Yu; K N Houk; Erik J Sorensen

doi:10.1021/jacs.1c09368

Pd(II)-Catalyzed Synthesis of Benzocyclobutenes by β-Methylene-Selective C(sp³)-H Arylation with a Transient Directing Group

J Am Chem Soc. 2021 Dec 8;143(48):20035-20041. doi: 10.1021/jacs.1c09368. Epub 2021 Nov 24.

Authors

Philip A Provencher¹, John F Hoskin¹, Jonathan J Wong², Xiangyang Chen², Jin-Quan Yu³, K N Houk², Erik J Sorensen¹

Affiliations

¹ Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
² Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
³ Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.

PMID: 34817163
DOI: 10.1021/jacs.1c09368

Abstract

Methylene-selective C-H functionalization is a significant hurdle that remains to be addressed in the field of Pd(II) catalysis. We report a Pd(II)-catalyzed synthesis of benzocyclobutenes by methylene-selective C(sp³)-H arylation of ketones. The reaction utilizes glycine as a transient directing group and a 2-pyridone ligand, which may govern the methylene selectivity by making intimate molecular associations with the substrate during concerted metalation-deprotonation. This reaction is shown to be highly selective for intramolecular methylene C(sp³)-H arylation, thus enabling sequential C(sp³)-H functionalization.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.