TY - JOUR
T1 - Nontraditional Fragment Couplings of Alcohols and Carboxylic Acids
T2 - C(sp3)-C(sp3) Cross-Coupling via Radical Sorting
AU - Sakai, Holt A.
AU - Macmillan, David W.C.
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/4/13
Y1 - 2022/4/13
N2 - Alcohols and carboxylic acids are among the most commercially abundant, synthetically versatile, and operationally convenient functional groups in organic chemistry. Under visible light photoredox catalysis, these native synthetic handles readily undergo radical activation, and the resulting open-shell intermediates can subsequently participate in transition metal catalysis. In this report, we describe the C(sp3)-C(sp3) cross-coupling of alcohols and carboxylic acids through the dual combination of N-heterocyclic carbene (NHC)-mediated deoxygenation and hypervalent iodine-mediated decarboxylation. This mild and practical Ni-catalyzed radical-coupling protocol was employed to prepare a wide array of alkyl-Alkyl cross-coupled products, including highly congested quaternary carbon centers from the corresponding tertiary alcohols or tertiary carboxylic acids. We demonstrate the synthetic applications of this methodology to alcohol C1-Alkylation and formal homologation, as well as to the late-stage functionalization of drugs, natural products, and biomolecules.
AB - Alcohols and carboxylic acids are among the most commercially abundant, synthetically versatile, and operationally convenient functional groups in organic chemistry. Under visible light photoredox catalysis, these native synthetic handles readily undergo radical activation, and the resulting open-shell intermediates can subsequently participate in transition metal catalysis. In this report, we describe the C(sp3)-C(sp3) cross-coupling of alcohols and carboxylic acids through the dual combination of N-heterocyclic carbene (NHC)-mediated deoxygenation and hypervalent iodine-mediated decarboxylation. This mild and practical Ni-catalyzed radical-coupling protocol was employed to prepare a wide array of alkyl-Alkyl cross-coupled products, including highly congested quaternary carbon centers from the corresponding tertiary alcohols or tertiary carboxylic acids. We demonstrate the synthetic applications of this methodology to alcohol C1-Alkylation and formal homologation, as well as to the late-stage functionalization of drugs, natural products, and biomolecules.
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U2 - 10.1021/jacs.2c02062
DO - 10.1021/jacs.2c02062
M3 - Article
C2 - 35353531
AN - SCOPUS:85127905136
SN - 0002-7863
VL - 144
SP - 6185
EP - 6192
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 14
ER -