TY - JOUR
T1 - LiCl-Accelerated multimetallic cross-coupling of aryl chlorides with aryl triflates
AU - Huang, Liangbin
AU - Ackerman, Laura K.G.
AU - Kang, Kai
AU - Parsons, Astrid M.
AU - Weix, Daniel J.
N1 - Funding Information:
The authors gratefully acknowledge funding from the NIH NIGMS (R01GM097243 to D.J.W.), the NSF (NSF DGE-1419118 to A.M.P. and L.K.G.A.), and SIOC (fellowship to K.K.). D.J.W. is a Camille Dreyfus Teacher-Scholar. Additional funding from Novartis and Boehringer Ingelheim is also gratefully acknowledged. We thank Amanda Spiewak (University of Wisconsin) for assistance in the Pd complex reduction study, Yixing Guo and Prof. Kara Bren (University of Rochester) for assistance in obtaining CV data, and Prof. Alison R. Fout for a helpful discussion on the mechanism of action for LiCl.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/6/30
Y1 - 2019/6/30
N2 - While the synthesis of biaryls has advanced rapidly in the past decades, cross-Ullman couplings of aryl chlorides, the most abundant aryl electrophiles, have remained elusive. Reported here is the first general cross-Ullman coupling of aryl chlorides with aryl triflates. The selectivity challenge associated with coupling an inert electrophile with a reactive one is overcome using a multimetallic strategy with the appropriate choice of additive. Studies demonstrate that LiCl is essential for effective cross-coupling by accelerating the reduction of Ni(II) to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts. The modified conditions tolerate a variety of functional groups on either coupling partner (42 examples), and examples include a three-step synthesis of flurbiprofen.
AB - While the synthesis of biaryls has advanced rapidly in the past decades, cross-Ullman couplings of aryl chlorides, the most abundant aryl electrophiles, have remained elusive. Reported here is the first general cross-Ullman coupling of aryl chlorides with aryl triflates. The selectivity challenge associated with coupling an inert electrophile with a reactive one is overcome using a multimetallic strategy with the appropriate choice of additive. Studies demonstrate that LiCl is essential for effective cross-coupling by accelerating the reduction of Ni(II) to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts. The modified conditions tolerate a variety of functional groups on either coupling partner (42 examples), and examples include a three-step synthesis of flurbiprofen.
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U2 - 10.1021/jacs.9b05461
DO - 10.1021/jacs.9b05461
M3 - Article
C2 - 31257881
AN - SCOPUS:85070024026
SN - 0002-7863
VL - 141
SP - 10978
EP - 10983
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 28
ER -