Mechanistic insight enables practical, scalable, room temperature Chan–Lam N-arylation of N-aryl sulfonamides
Abstract
Sulfonamides are profoundly important in pharmaceutical design. C–N cross-coupling of sulfonamides is an effective method for fragment coupling and structure–activity relationship (SAR) mining. However, cross-coupling of the important N-arylsulfonamide pharmacophore has been notably unsuccessful. Here, we present a solution to this problem via oxidative Cu-catalysis (Chan–Lam cross-coupling). Mechanistic insight has allowed the discovery and refinement of an effective cationic Cu catalyst to facilitate the practical and scalable Chan–Lam N-arylation of primary and secondary N-arylsulfonamides at room temperature. We also demonstrate utility in the large scale synthesis of a key intermediate to a clinical hepatitis C virus treatment.
Citation
Vantourout , J C , Li , L , Bendito-Moll , E , Chabbra , S , Arrington , K , Bode , B E , Isidro-Llobet , A , Kowalski , J A , Nilson , M G , Wheelhouse , K M P , Woodard , J L , Xie , S , Leitch , D C & Watson , A J B 2018 , ' Mechanistic insight enables practical, scalable, room temperature Chan–Lam N -arylation of N -aryl sulfonamides ' , ACS Catalysis , vol. 8 , pp. 9560-9566 . https://doi.org/10.1021/acscatal.8b03238
Publication
ACS Catalysis
Status
Peer reviewed
ISSN
2155-5435Type
Journal article
Description
The authors thank the EPSRC and GSK for a studentship (JCV).Collections
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