The reactivity of tetrahydropyrrolo[1,2-b]isothiazol-3(2H)-one 1,1-dioxides

• Published in: Monatshefte für Chemie 2020-11, Vol.151 (11), p.1759-1772
• Main Authors: Omelian, Taras V., Dobrydnev, Alexey V., Utchenko, Oleksandr Yu, Ostapchuk, Eugeniy N., Konovalova, Irina S., Volovenko, Yulian M.
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Inorganic Chemistry; Organic Chemistry; Original Paper; Physical Chemistry; Theoretical and Computational Chemistry
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-020-02694-3

The present work is devoted to the study of the reactivity of tetrahydropyrrolo[1,2- b ]isothiazol-3(2 H )-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(2 H )-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 (Ph 3 P=CHCO 2 Me). 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