Abstract

The present work is devoted to the study of the reactivity of tetrahydropyrrolo[1,2-b]isothiazol-3(2H)-one 1,1-dioxide framework. This scaffold possesses two reaction centers: the EWG-activated methylene group and the carbonyl functionality, which are the basic variation points. At the same time, the attached 3a-substituent had a significant impact on the course of the explored reactions and its role was also investigated. In this regard, the corresponding 3a-unsubstituted and 3a-methylated tetrahydropyrrolo[1,2-b]isothiazol-3(2H)-one 1,1-dioxides were chosen as model substances involved in chemical properties evaluation. With a view to pre-assess the activity of the model compounds, a deuteration study was conducted. Furthermore, the interaction with a variety of electrophilic and nucleophilic agents was explored. The most striking difference in the chemical behavior was observed in the reaction with the Wittig reagent triphenylcarbethoxymethylenephosphorane (Ph₃P=CHCO₂Me). In particular, unlike the 3a-unsubstituted substrate, the 3a-methylated one gave the unusual phosphonium betaine, namely 3a-methyl-2-[2-(triphenylphosphonio)acetyl]-3a,4,5,6-tetrahydropyrrolo[1,2-b]isothiazol-3-olate 1,1-dioxide. The proposed mechanistic insights of this reaction have been discovered.

Graphic abstract

中文翻译：

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四氢吡咯并[1,2-b]异噻唑-3（2 H）-1,1-二氧化物的反应活性

摘要

本工作致力于四氢吡咯并[1,2 - b ]异噻唑-3（2H）-1,1-二氧化物骨架的反应性研究。该支架具有两个反应中心：EWG活化的亚甲基和羰基官能度，这是基本的变化点。同时，附着的3a取代基对所探索反应的进程有重大影响，并且还研究了其作用。在这方面，相应的3a-未取代和3a-甲基化的四氢吡咯并[1,2 - b ]异噻唑-3（2 H）-选择一种1,1-二氧化物作为参与化学性质评估的模型物质。为了预先评估模型化合物的活性，进行了氘化研究。此外，还探讨了与各种亲电子试剂和亲核试剂的相互作用。在与Wittig试剂三苯基碳乙氧基亚甲基磷烷（Ph ₃ P = CHCO ₂ Me）的反应中，观察到最明显的化学行为差异。特别地，与3a-未取代的底物不同，3a-甲基化的底物产生了不同寻常的beta甜菜碱，即3a-甲基-2- [2-（2-（三苯基膦酰基）乙酰基] -3a，4,5,6-四氢吡咯并[1,2] - b ]异噻唑-3-醇钠1,1-二氧化物。已经发现了该反应的建议机理见解。

图形摘要