- Selective Late-Stage Sulfonyl Chloride Formation from Sulfonamides Enabled by Pyry-BF4
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Reported here is a simple and practical functionalization of primary sulfonamides, by means of a pyrylium salt (Pyry-BF4), with nucleophiles. This simple reagent activates the poorly nucleophilic NH2 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-BF4 towards NH2 groups permit the formation of sulfonyl chlorides in a late-stage fashion, tolerating a preponderance of sensitive functionalities.
- Gómez-Palomino, Alejandro,Cornella, Josep
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supporting information
p. 18235 - 18239
(2019/11/13)
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- Cyclopropanesulfonyl Chloride: Its Mechanism of Hydrolysis and Reactions with Tertiary Amines in Organic Media
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Cyclopropanesulfonyl chloride (1) has been synthesized and its reactions examined to see if the three-membered ring leads to unusual reactions in either 1 or the corresponding sulfene, cyclopropanethione S,S-dioxide (2). pH-rate profiles, primary kinetic isotope effects (KIE's), and pH-product ratio experiments are in full agreement with mechanisms of hydrolysis of 1 like those of a simple alkanesulfonyl chlorides (J.Am.Chem.Soc.1992,114,1743-1749), specifically, (a) below pH 7.2 by SN2-S reaction with water and (b) above pH 7.3, elimination by hydroxide to form the sulfene (2) which is trapped by (i) water below pH 12.0 and (ii) hydroxide above pH 12.0.The products of the reaction of cyclopropanesulfonyl-1-d chloride (9) with triethylamine and 2-propanol in dichloromethane indicate that most of the reaction goes via 2; the analogous reaction with trimethylamine apparently proceeds by a direct formation of the sulfonylammonium chloride (14) which then yields the α-deuterated N,N-dimethyl sulfonamide (12, R=Me).The evident sulfene formation processes in the reaction of triethylamine with ethenesulfonyl, 2-propanesulfonyl, and cyclopropanesulfonyl chlorides show very low primary KIE's (1.5), pointing to highly product-like transition states.Reaction of 1 with an enamine (1-pyrrolidino-2-methylpropene, 20) in the presence of a base in either water or dichloromethane gave cyclopropanesulfonpyrrolidide (23) and an aldehyde adduct (24), but no four-membered cycloadduct (21).
- King, James F.,Lam, Joe Y. L.,Ferrazzi, Gabriele
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p. 1128 - 1135
(2007/10/02)
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