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

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

Chemistry

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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.

Original language	English (US)
Pages (from-to)	20035-20041
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	143
Issue number	48
DOIs	https://doi.org/10.1021/jacs.1c09368
State	Published - Dec 8 2021

All Science Journal Classification (ASJC) codes

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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

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.",

author = "Provencher, {Philip A.} and Hoskin, {John F.} and Wong, {Jonathan J.} and Xiangyang Chen and Yu, {Jin Quan} and Houk, {K. N.} and Sorensen, {Erik J.}",

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T1 - Pd(II)-Catalyzed Synthesis of Benzocyclobutenes by β-Methylene-Selective C(sp3)-H Arylation with a Transient Directing Group

AU - Provencher, Philip A.

AU - Hoskin, John F.

AU - Wong, Jonathan J.

AU - Chen, Xiangyang

AU - Yu, Jin Quan

AU - Houk, K. N.

AU - Sorensen, Erik J.

PY - 2021/12/8

Y1 - 2021/12/8

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AB - 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.

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

Abstract

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