Potassium Tert-butoxide Mediated Benzyl Radical Generation From Halo Compounds and Multi-Component Reactions With Selenourea and Carboxylic Acids for the Synthesis of Selenoesters

Abstract

Selenoesters are precursors for Native Chemical Ligation (NCL), and diselenide-selenoester ligation (DSL), which are essential chemical processes for protein synthesis. They also act as synthons for the generation of acyl radicals, hydrogen selenide, and selenoacids. Selenoesters can potentially be used to prepare amino acid conjugates via amidation reaction. Generally, selenoesters synthesis from carboxylic acids involves two steps, conversion to acyl chlorides and followed by reaction with diselenides. A new multicomponent reaction for the synthesis of selenoesters directly from carboxylic acids, selenourea, alkyl/aryl/allyl halides is reported. Potassium-tert-butoxide (t-BuOK) acts as a radical initiator for generation of benzyl radicals from halo compounds under microwave heating. Selenourea acted as source of selenium, and potassium-tert-butoxide played dual role, as a base and a radical initiator. A new reaction mechanism is proposed and the reaction proceeds via a benzyl radical intermediate. The radical intermediate was trapped by a radical quencher (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) and it was isolated, characterized by 1H and 13C NMR in order to prove the proposed new mechanism. The selenoesters were isolated in a moderate to good yields, and the reaction is well tolerated with several aromatic carboxylic acids. The reaction was also suitable for benzylic and allylic halo compounds, and aryl sulfonates.