Diastereoselective Construction of Structurally Diverse Spirooxindoles via Annulation of Morita-Baylis-Hillman Adducts of Isatin

Abstract

The carbon−carbon bond forming reactions have always remained as one of the most indispensable reactions in organic synthesis. Among various carbon−carbon bond forming reactions, the Morita−Baylis−Hillman (MBH) reaction is one of the very useful and potential transformations with enormous synthetic utility. The dense functionalities and versatile reactivity of Morita-Baylis-Hillman (MBH) adducts make them powerful precursors for building various carbocyclic, heterocyclic and other important compounds of biological significance. In recent the years, isatin-derived Morita-Baylis-Hillman (MBH) carbonates have emerged as versatile synthons for constructing multi-functional spirooxindole scaffolds under organocatalytic conditions. In this thesis novel uses of MBH carbonates of isatin have been explored for the efficient organocatalytic transformations to synthesize useful scaffolds such as spiroheterocycles. Various interesting and useful spiroheterocycles such as bis-spirooxindoles, cyclopropyl spirooxindoles, spirooxindole dihydofuran fused pyrazolones, spirocyclopentadienes, cyclopenetene spirooxindoles and spirooxindole dihydopyrrole fused pyrazolones have been synthesized by utilizing Morita-Baylis-Hillman carbonates of isatin under tertiary amine catalysis. We have developed highly efficient organocatalytic [3+2] and [2+1] annulations between isatin-derived Morita−Baylis−Hillman carbonate and 3-methyleneoxindoles to access bis-spirooxindoles appended with cyclopentene and cyclopropane derivatives. Later, we explored the utility of cinchona derived chiral tertiary amine catalyst in the cycloaddition between isatin-derived Morita−Baylis−Hillman adducts and pyrazolone 4, 5-diones to construct enantiopure spirooxindole dihydrofuran fused pyrazolones scaffold. We have successfully employed aurones and thioaurones as a suitable C2 synthon in [3+2] annulation with MBH carbonates of isatin to construct structurally diverse and multi-functionalized sprio fused carbopentacyclic scaffold under suitable Lewis base catalysis. Further, we have also synthesized the spirooxindole dihydropyrrole fused pyrazolone derivatives utilizing Morita−Baylis−Hillman carbonates of isatins and pyrazolone derived ketimines under DMAP catalysis.