TY - JOUR
T1 - Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source
AU - Kariofillis, Stavros K.
AU - Shields, Benjamin J.
AU - Tekle-Smith, Makeda A.
AU - Zacuto, Michael J.
AU - Doyle, Abigail G.
N1 - Funding Information:
This material is based on work supported by the National Science Foundation Graduate Research Fellowship Program under Grant Number DGE-1656466 (to S.K.K.). M.A.T.-S. wishes to thank Princeton’s Presidential Postdoctoral Fellowship for funding. A.G.D. gratefully acknowledges Celgene, Princeton Innovation Fund, and NIGMS (R35 GM126986) for financial support. We thank Prof. David MacMillan and Dr. Laura K. G. Ackerman for helpful suggestions.
Publisher Copyright:
© 2020 American Chemical Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/22
Y1 - 2020/4/22
N2 - 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.
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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U2 - 10.1021/jacs.0c02805
DO - 10.1021/jacs.0c02805
M3 - Article
C2 - 32275411
AN - SCOPUS:85083366970
VL - 142
SP - 7683
EP - 7689
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 16
ER -