Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source

Stavros K. Kariofillis; Benjamin J. Shields; Makeda A. Tekle-Smith; Michael J. Zacuto; Abigail G. Doyle

doi:10.1021/jacs.0c02805

Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source

Stavros K. Kariofillis, Benjamin J. Shields, Makeda A. Tekle-Smith, Michael J. Zacuto, Abigail G. Doyle

Research output: Contribution to journal › Article

2 Scopus citations

Abstract

Methylation of organohalides represents a valuable transformation, but typically requires harsh reaction conditions or reagents. We report a radical approach for the methylation of (hetero)aryl chlorides using nickel/photoredox catalysis wherein trimethyl orthoformate, a common laboratory solvent, serves as a methyl source. This method permits methylation of (hetero)aryl chlorides and acyl chlorides at an early and late stage with broad functional group compatibility. Mechanistic investigations indicate that trimethyl orthoformate serves as a source of methyl radical via β-scission from a tertiary radical generated upon chlorine-mediated hydrogen atom transfer.

Original language	English (US)
Pages (from-to)	7683-7689
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	142
Issue number	16
DOIs	https://doi.org/10.1021/jacs.0c02805
State	Published - Apr 22 2020

All Science Journal Classification (ASJC) codes

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

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10.1021/jacs.0c02805

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Kariofillis, S. K., Shields, B. J., Tekle-Smith, M. A., Zacuto, M. J., & Doyle, A. G. (2020). Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source. Journal of the American Chemical Society, 142(16), 7683-7689. https://doi.org/10.1021/jacs.0c02805

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abstract = "Methylation of organohalides represents a valuable transformation, but typically requires harsh reaction conditions or reagents. We report a radical approach for the methylation of (hetero)aryl chlorides using nickel/photoredox catalysis wherein trimethyl orthoformate, a common laboratory solvent, serves as a methyl source. This method permits methylation of (hetero)aryl chlorides and acyl chlorides at an early and late stage with broad functional group compatibility. Mechanistic investigations indicate that trimethyl orthoformate serves as a source of methyl radical via β-scission from a tertiary radical generated upon chlorine-mediated hydrogen atom transfer.",

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Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source. / Kariofillis, Stavros K.; Shields, Benjamin J.; Tekle-Smith, Makeda A.; Zacuto, Michael J.; Doyle, Abigail G.

In: Journal of the American Chemical Society, Vol. 142, No. 16, 22.04.2020, p. 7683-7689.

Research output: Contribution to journal › Article

TY - JOUR

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AB - Methylation of organohalides represents a valuable transformation, but typically requires harsh reaction conditions or reagents. We report a radical approach for the methylation of (hetero)aryl chlorides using nickel/photoredox catalysis wherein trimethyl orthoformate, a common laboratory solvent, serves as a methyl source. This method permits methylation of (hetero)aryl chlorides and acyl chlorides at an early and late stage with broad functional group compatibility. Mechanistic investigations indicate that trimethyl orthoformate serves as a source of methyl radical via β-scission from a tertiary radical generated upon chlorine-mediated hydrogen atom transfer.

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