Metallaphotoredox Perfluoroalkylation of Organobromides

Xiangbo Zhao; David W.C. MacMillan

doi:10.1021/jacs.0c09977

Metallaphotoredox Perfluoroalkylation of Organobromides

Xiangbo Zhao, David W.C. MacMillan

Chemistry

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

Abstract

Ruppert-Prakash type reagents (TMSCF3, TMSC2F5, and TMSC3F7) are readily available, air-stable, and easy-to-handle fluoroalkyl sources. Herein, we describe a mild, copper-catalyzed cross-coupling of these fluoroalkyl nucleophiles with aryl and alkyl bromides to produce a diverse array of trifluoromethyl, pentafluoroethyl, and heptafluoropropyl adducts. This light-mediated transformation proceeds via a silyl-radical-mediated halogen atom abstraction pathway, which enables perfluoroalkylation of a broad range of organobromides of variable steric and electronic demand. The utility of the method is demonstrated through the late-stage functionalization of several drug analogues.

Original language	English (US)
Pages (from-to)	19480-19486
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	142
Issue number	46
DOIs	https://doi.org/10.1021/jacs.0c09977
State	Published - Nov 18 2020

All Science Journal Classification (ASJC) codes

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

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10.1021/jacs.0c09977

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title = "Metallaphotoredox Perfluoroalkylation of Organobromides",

abstract = "Ruppert-Prakash type reagents (TMSCF3, TMSC2F5, and TMSC3F7) are readily available, air-stable, and easy-to-handle fluoroalkyl sources. Herein, we describe a mild, copper-catalyzed cross-coupling of these fluoroalkyl nucleophiles with aryl and alkyl bromides to produce a diverse array of trifluoromethyl, pentafluoroethyl, and heptafluoropropyl adducts. This light-mediated transformation proceeds via a silyl-radical-mediated halogen atom abstraction pathway, which enables perfluoroalkylation of a broad range of organobromides of variable steric and electronic demand. The utility of the method is demonstrated through the late-stage functionalization of several drug analogues.",

author = "Xiangbo Zhao and MacMillan, {David W.C.}",

note = "Funding Information: Financial support was provided by the National Institute of General Medical Sciences (NIGMS), the NIH (under Award R35GM134897-01), the Princeton Catalysis Initiative, and kind gifts from Merck, Janssen, BMS, Genentech, Celgene and Pfizer. X.B. is grateful for a postdoctoral fellowship from the Shanghai Institute of Organic Chemistry. We thank Yufan Liang, Ian Perry, Xiaheng Zhang, Wei Liu, and Vlad Bacauanu for their help in preparing this paper.",

year = "2020",

month = nov,

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doi = "10.1021/jacs.0c09977",

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T1 - Metallaphotoredox Perfluoroalkylation of Organobromides

AU - Zhao, Xiangbo

AU - MacMillan, David W.C.

N1 - Funding Information: Financial support was provided by the National Institute of General Medical Sciences (NIGMS), the NIH (under Award R35GM134897-01), the Princeton Catalysis Initiative, and kind gifts from Merck, Janssen, BMS, Genentech, Celgene and Pfizer. X.B. is grateful for a postdoctoral fellowship from the Shanghai Institute of Organic Chemistry. We thank Yufan Liang, Ian Perry, Xiaheng Zhang, Wei Liu, and Vlad Bacauanu for their help in preparing this paper.

PY - 2020/11/18

Y1 - 2020/11/18

N2 - Ruppert-Prakash type reagents (TMSCF3, TMSC2F5, and TMSC3F7) are readily available, air-stable, and easy-to-handle fluoroalkyl sources. Herein, we describe a mild, copper-catalyzed cross-coupling of these fluoroalkyl nucleophiles with aryl and alkyl bromides to produce a diverse array of trifluoromethyl, pentafluoroethyl, and heptafluoropropyl adducts. This light-mediated transformation proceeds via a silyl-radical-mediated halogen atom abstraction pathway, which enables perfluoroalkylation of a broad range of organobromides of variable steric and electronic demand. The utility of the method is demonstrated through the late-stage functionalization of several drug analogues.

AB - Ruppert-Prakash type reagents (TMSCF3, TMSC2F5, and TMSC3F7) are readily available, air-stable, and easy-to-handle fluoroalkyl sources. Herein, we describe a mild, copper-catalyzed cross-coupling of these fluoroalkyl nucleophiles with aryl and alkyl bromides to produce a diverse array of trifluoromethyl, pentafluoroethyl, and heptafluoropropyl adducts. This light-mediated transformation proceeds via a silyl-radical-mediated halogen atom abstraction pathway, which enables perfluoroalkylation of a broad range of organobromides of variable steric and electronic demand. The utility of the method is demonstrated through the late-stage functionalization of several drug analogues.

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