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Selective Late‐Stage Sulfonyl Chloride Formation from Sulfonamides Enabled by Pyry‐BF 4
Author(s) -
GómezPalomino Alejandro,
Cornella Josep
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201910895
Subject(s) - sulfonyl , chemistry , sulfonamide , nucleophile , electrophile , reagent , chloride , organic chemistry , combinatorial chemistry , selectivity , salt (chemistry) , medicinal chemistry , catalysis , alkyl
Reported here is a simple and practical functionalization of primary sulfonamides, by means of a pyrylium salt (Pyry‐BF 4 ), with nucleophiles. This simple reagent activates the poorly nucleophilic NH 2 group in a sulfonamide, enabling the formation of one of the best electrophiles in organic synthesis: a sulfonyl chloride. Because of the variety of primary sulfonamides in pharmaceutical contexts, special attention has been focused on the direct conversion of densely functionalized primary sulfonamides by a late‐stage formation of the corresponding sulfonyl chloride. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides, sulfonates, sulfides, sulfonyl fluorides, and sulfonic acids. The mild reaction conditions and the high selectivity of Pyry‐BF 4 towards NH 2 groups permit the formation of sulfonyl chlorides in a late‐stage fashion, tolerating a preponderance of sensitive functionalities.