Mechanistic insight enables practical, scalable, room temperature Chan–Lam N-arylation of N-aryl sulfonamides
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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.
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
Copyright © 2018 American Chemical Society. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1021/acscatal.8b03238
DescriptionThe authors thank the EPSRC and GSK for a studentship (JCV).
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