Selective Late-Stage Sulfonyl Chloride Formation from Sulfonamides Enabled by Pyry-BF4
Selective Late-Stage Sulfonyl Chloride Formation from Sulfonamides Enabled by Pyry-BF4
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DOI：
10.1002/anie.201910895
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发表时间：
2019-10-28
影响因子：
16.6
通讯作者：
Cornella, Josep
中科院分区：
文献类型：
--
作者：
Gomez-Palomino, Alejandro;Cornella, Josep
本文报道了一种简单而实用的伯磺酰胺的官能化，通过吡喃盐（Pyry-BF 4），与亲核试剂。这种简单的试剂可以激活磺酰胺中的弱亲核性NH 2基团，从而形成有机合成中最好的亲电子试剂之一：磺酰氯。由于在制药环境中的伯磺酰胺的多样性，特别关注通过相应磺酰氯的后期形成直接转化密集官能化的伯磺酰胺。各种亲核试剂可以参与这种转化，从而允许合成复杂的磺酰胺、磺酸盐、硫化物、磺酰氟和磺酸。温和的反应条件和Pyry-BF 4对NH 2基团的高选择性允许在后期形成磺酰氯，耐受敏感官能团的优势。
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.