Effect of Nucleophile Deprotonation on SuFEx: Synthesis of Sulfonamides

Abstract

In a quest for efficient SuFEx-type transformations we studied reactions of amines with 4-fluorobenzenesulfonyl fluoride. The substrate may react by fluoride substitution at the aromatic ring (S_NAr) and at the sulfonyl group (SuFEx). Analysis of the reaction course revealed that deprotonation of the N-nucleophile controls the reaction course: neutral amines in DMF attack at the aromatic ring, whereas amine anions, generated in equilibrium with LiHMDS in toluene, favor sulfonyl substitution. Using the base-promoted conditions we synthesized a set of substituted sulfonamides in high yields.

Key words

SuFEx - sulfonyl fluorides - amines - sulfonamides - nucleophilic substitution

Publication History

Received: 24 July 2024

Accepted after revision: 21 October 2024

Accepted Manuscript online:
21 October 2024

Article published online:
18 November 2024

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