Mechanistic insight enables practical, scalable, room temperature Chan–Lam N-arylation of N-aryl sulfonamides

Julien C. Vantourout; Ling Li; Enrique Bendito-Moll; Sonia Chabbra; Kenneth Arrington; Bela E. Bode; Albert Isidro-Llobet; John A. Kowalski; Mark G. Nilson; Katherine M. P. Wheelhouse; John L. Woodard; Shiping Xie; David C. Leitch; Allan J. B. Watson

doi:10.1021/acscatal.8b03238

Mechanistic insight enables practical, scalable, room temperature Chan–Lam N-arylation of N-aryl sulfonamides

Julien C. Vantourout, Ling Li, Enrique Bendito-Moll, Sonia Chabbra, Kenneth Arrington, Bela E. Bode, Albert Isidro-Llobet, John A. Kowalski, Mark G. Nilson, Katherine M. P. Wheelhouse, John L. Woodard, Shiping Xie, David C. Leitch, Allan J. B. Watson

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	9560-9566
Number of pages	7
Journal	ACS Catalysis
Volume	8
Early online date	6 Sept 2018
DOIs	https://doi.org/10.1021/acscatal.8b03238
Publication status	E-pub ahead of print - 6 Sept 2018

Keywords

Boronic acid
Boronic ester
Catalysis
Chan-Lam
Copper
Sulfonamide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acscatal.8b03238

Vantourout_2018_ACSC_Mechanisticinsight_AAM
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
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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, 8, 9560-9566. Advance online publication. https://doi.org/10.1021/acscatal.8b03238

@article{480b468588e944f8a585e428ef1a84f2,

title = "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.",

keywords = "Boronic acid, Boronic ester, Catalysis, Chan-Lam, Copper, Sulfonamide",

author = "Vantourout, \{Julien C.\} and Ling Li and Enrique Bendito-Moll and Sonia Chabbra and Kenneth Arrington and Bode, \{Bela E.\} and Albert Isidro-Llobet and Kowalski, \{John A.\} and Nilson, \{Mark G.\} and Wheelhouse, \{Katherine M. P.\} and Woodard, \{John L.\} and Shiping Xie and Leitch, \{David C.\} and Watson, \{Allan J. B.\}",

note = "The authors thank the EPSRC and GSK for a studentship (JCV).",

year = "2018",

month = sep,

day = "6",

doi = "10.1021/acscatal.8b03238",

language = "English",

volume = "8",

pages = "9560--9566",

journal = "ACS Catalysis",

issn = "2155-5435",

publisher = "American Chemical Society (ACS)",

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Vantourout, JC, Li, L, Bendito-Moll, E, Chabbra, S, Arrington, K, Bode, BE, Isidro-Llobet, A, Kowalski, JA, Nilson, MG, Wheelhouse, KMP, Woodard, JL, Xie, S, Leitch, DC & Watson, AJB 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

TY - JOUR

T1 - Mechanistic insight enables practical, scalable, room temperature Chan–Lam N-arylation of N-aryl sulfonamides

AU - Vantourout, Julien C.

AU - Li, Ling

AU - Bendito-Moll, Enrique

AU - Chabbra, Sonia

AU - Arrington, Kenneth

AU - Bode, Bela E.

AU - Isidro-Llobet, Albert

AU - Kowalski, John A.

AU - Nilson, Mark G.

AU - Wheelhouse, Katherine M. P.

AU - Woodard, John L.

AU - Xie, Shiping

AU - Leitch, David C.

AU - Watson, Allan J. B.

N1 - The authors thank the EPSRC and GSK for a studentship (JCV).

PY - 2018/9/6

Y1 - 2018/9/6

N2 - 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.

AB - 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.

KW - Boronic acid

KW - Boronic ester

KW - Catalysis

KW - Chan-Lam

KW - Copper

KW - Sulfonamide

UR - https://www.scopus.com/pages/publications/85053679390

U2 - 10.1021/acscatal.8b03238

DO - 10.1021/acscatal.8b03238

M3 - Article

SN - 2155-5435

VL - 8

SP - 9560

EP - 9566

JO - ACS Catalysis

JF - ACS Catalysis

ER -

Mechanistic insight enables practical, scalable, room temperature Chan–Lam N-arylation of N-aryl sulfonamides

Abstract

Keywords

UN SDGs

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