TY - JOUR
T1 - Cross-Electrophile Coupling of Unactivated Alkyl Chlorides
AU - Sakai, Holt A.
AU - Liu, Wei
AU - Le, Chi
AU - MacMillan, David W.C.
N1 - Funding Information:
The authors are grateful for financial support provided by the National Institute of General Medical Sciences (NIGMS), the NIH (under award no. R35GM134897-01), the Princeton Catalysis Initiative, and kind gifts from Merck, Janssen, BMS, Genentech, Celgene and Pfizer. H.A.S acknowledges Princeton University for a first-year fellowship and acknowledges Princeton University, E. Taylor, and the Taylor family for an Edward C. Taylor Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS. The authors thank P. Jeffrey for assistance with X-ray structure determination and I. Pelczer for assistance with NMR structure determination.
Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/7/8
Y1 - 2020/7/8
N2 - Alkyl chlorides are bench-stable chemical feedstocks that remain among the most underutilized electrophile classes in transition metal catalysis. Overcoming intrinsic limitations of C(sp3)-Cl bond activation, we report the development of a novel organosilane reagent that can participate in chlorine atom abstraction under mild photocatalytic conditions. In particular, we describe the application of this mechanism to a dual nickel/photoredox catalytic protocol that enables the first cross-electrophile coupling of unactivated alkyl chlorides and aryl chlorides. Employing these low-toxicity, abundant, and commercially available organochloride building blocks, this methodology allows access to a broad array of highly functionalized C(sp2)-C(sp3) coupled adducts, including numerous drug analogues.
AB - Alkyl chlorides are bench-stable chemical feedstocks that remain among the most underutilized electrophile classes in transition metal catalysis. Overcoming intrinsic limitations of C(sp3)-Cl bond activation, we report the development of a novel organosilane reagent that can participate in chlorine atom abstraction under mild photocatalytic conditions. In particular, we describe the application of this mechanism to a dual nickel/photoredox catalytic protocol that enables the first cross-electrophile coupling of unactivated alkyl chlorides and aryl chlorides. Employing these low-toxicity, abundant, and commercially available organochloride building blocks, this methodology allows access to a broad array of highly functionalized C(sp2)-C(sp3) coupled adducts, including numerous drug analogues.
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U2 - 10.1021/jacs.0c04812
DO - 10.1021/jacs.0c04812
M3 - Article
C2 - 32564602
AN - SCOPUS:85088210871
SN - 0002-7863
VL - 142
SP - 11691
EP - 11697
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 27
ER -