Issue 46, 2023

Kinetically-driven reactivity of sulfinylamines enables direct conversion of carboxylic acids to sulfinamides

Abstract

Sulfinamides are some of the most centrally important four-valent sulfur compounds that serve as critical entry points to an array of emergent medicinal functional groups, molecular tools for bioconjugation, and synthetic intermediates including sulfoximines, sulfonimidamides, and sulfonimidoyl halides, as well as a wide range of other S(IV) and S(VI) functionalities. Yet, the accessible chemical space of sulfinamides remains limited, and the approaches to sulfinamides are largely confined to two-electron nucleophilic substitution reactions. We report herein a direct radical-mediated decarboxylative sulfinamidation that for the first time enables access to sulfinamides from the broad and structurally diverse chemical space of carboxylic acids. Our studies show that the formation of sulfinamides prevails despite the inherent thermodynamic preference for the radical addition to the nitrogen atom, while a machine learning-derived model facilitates prediction of the reaction efficiency based on computationally generated descriptors of the underlying radical reactivity.

Graphical abstract: Kinetically-driven reactivity of sulfinylamines enables direct conversion of carboxylic acids to sulfinamides

Supplementary files

Article information

Article type
Edge Article
Submitted
07 sen 2023
Accepted
08 okt 2023
First published
09 okt 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2023,14, 13384-13391

Kinetically-driven reactivity of sulfinylamines enables direct conversion of carboxylic acids to sulfinamides

H. T. Dang, A. Porey, S. Nand, R. Trevino, P. Manning-Lorino, W. B. Hughes, S. O. Fremin, W. T. Thompson, S. K. Dhakal, H. D. Arman and O. V. Larionov, Chem. Sci., 2023, 14, 13384 DOI: 10.1039/D3SC04727J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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