Exploration of Morita-Baylis-Hillman Adducts of Pyrazoledione and 3-Methyleneoxindole to Access Multifunctional Spiroheterocycles with Contiguous Chiral Centres

Abstract

Organocatalysis has become one of the essential pillars of asymmetric catalysis, complementing enzyme and chiral metal catalysis. Over the last few decades, various carbon-carbon and carbon-hetero (C-C and C-X) bond-forming reactions such as the aldol reaction, Diels-Alder reaction, Mannich reaction, Friedel-Craft reaction, Morita-Baylis-Hillman (MBH) reaction, Stetter reaction, etc. have been explored under organocatalytic condition. Among these, the Morita-Baylis-Hillman (MBH) reaction has become one of the most important, popular, and versatile methods for constructing C-C, C-X bonds. The dense functionalities and versatile reactivity of Morita-Baylis-Hillman (MBH) adducts make them powerful precursors for building various carbocyclic, heterocyclic, and biologically important compounds. In recent years, pyrazolonone-derived MBH carbonates have emerged as a versatile synthon for constructing multi-functional spiropyrazolonone scaffolds under organocatalytic conditions.

We have been working in the field of organocatalysis over the years. We have effectively utilized the Morita-Baylis-Hillman carbonates of pyrazolonone and 3-Methylene Oxindole to construct different spiroheterocycles. Diastereoselective bis-spiropyrazolonone and spirooxindole have been successfully synthesized under tertiary amine catalysis. These spiroheterocycles have been synthesized via (3+2) cycloaddition pathway. Later, we explored the photoreactivity of 3-methylene oxindole under visible light irradiation to construct highly diastereoselective 3-4 fused spirooxindoles in one pot. Interestingly, this light-driven diasterioselective (4+2) cyclization occurs at an unusual unactivated C4 position (of 3-methylene Oxindole) without requiring any pre-functionalization. Further, we have successfully demonstrated the base catalyzed diastereoselective synthesis of tetraazadispiro pyrazolone framework via oxa-Michael cascade (4 + 2) annulation in a rapid reaction time (2 mins). Further, we extended the scope of base catalysed transformation for the diastereoselective synthesis of spiropyrazolone fused pyrolidines in rapid time (5-20 min).