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. 2024 Feb 2;89(3):1898-1909.
doi: 10.1021/acs.joc.3c02557. Epub 2024 Jan 18.

Nitro-sulfinate Reductive Coupling to Access (Hetero)aryl Sulfonamides

Sandra E Gatarz  1 , Oliver M Griffiths  1 , Henrique A Esteves  1 , Wenhua Jiao  1 , Peter Morse  2 , Ethan L Fisher  2 , David C Blakemore  2 , Steven V Ley  1
Affiliations

Nitro-sulfinate Reductive Coupling to Access (Hetero)aryl Sulfonamides

Sandra E Gatarz et al. J Org Chem. .

Abstract

A method to assemble (hetero)aryl sulfonamides via the reductive coupling of aryl sulfinates and nitroarenes is reported. Various reducing conditions with sodium bisulfite and with or without tin(II) chloride in DMSO were developed using an ultrasound bath to improve reaction homogeneity and mixing. A range of (hetero)aryl sulfonamides bearing a selection of functional groups were prepared, and the mechanism of the transformation was investigated. These investigations have led us to propose the formation of nitrosoarene intermediates, which were established via an independent molecular coupling strategy.

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Conflict of interest statement

The authors declare the following competing financial interest(s): The authors declare no competing financial interest(s) other than WJ, PM, ELF and DCB are employees and stockholders of Pfizer Inc.

Figures

Figure 1
Figure 1
Drugs containing (hetero)aryl sulfonamides.
Scheme 1
Scheme 1. (a–e) Previously Reported Nitro-sulfinate Reductive Coupling Strategies as Alternative S–N Bond-Forming Reactions
Scheme 2
Scheme 2. a) Control Experiment Using N-Phenyl Hydroxylamine (5), (b) Control Experiment Using Azobenzene Dioxide (6a), (c) Dissolution-Influenced Equilibrium of Azobenzene Dioxide 6a and Nitrosobenzene (6b), (d) Sodium Bisulfite-Mediated Reduction of N-Sulfonyl Hydroxylamine 7, and (e) Control Experiment Using a Slowly Added Solution of Nitrosobenzene (6b)
Scheme 3
Scheme 3. Proposed Reaction Mechanism
See this image and copyright information in PMC

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