CONSTRUCTION OF SPIROCYCLIC AND PYRROLOCOUMARIN TETHERED POLYCYCLIC SCAFFOLDS AND SUCCINIMIDE DERIVATIVES

Abstract

The thesis entitled “Construction of Spirocyclic and Pyrrolo-coumarin Tethered Polycyclic Scaffolds and Succinimide Derivatives” is divided into three chapters, viz. (i) Introduction, (ii) Objectives, Results and Discussion, and (iii) Experimental. Chapter 1: Introduction In this chapter, synthetic aspects of the polycyclic spirocyclized and polyheterocyclic compounds embedded with pyrrole moiety are discussed. Synthesis of templates with biological importance and having similarities to natural product structures is highly efficient. Owing to their incorporation in a broad range of bioactive natural products, spiro heterocyclic scaffolds have uplifted enormous research interest among synthetic organic and medicinal chemists. Present reaction methodologies provide an efficient way for the synthesis of polycyclic compounds. Polyheterocyclic compounds are found as the main constituent in many drugs and other biologically active compounds like ningallins. The reactions occur in one-pot manner via the construction of multiple bonds such as C–C, C–N, C–S to deliver multifunctional and polycyclic and acyclic compounds. Polycyclic and polyheterocyclic compounds have been synthesized by cycloaddition reactions of functionally active components and acyclic vinyl amines and sulfides have been synthesized via addition elimination reaction. The reactions are highly efficient and are environmentally benign generating molecular complexity without producing hazardous side products. Reactions of acenaphthaquinone-based compounds and indanones, arylidene succinimides and benzoxazinones resulting in the formation of polycyclic, spirocyclized and heterocyclic compouds have been depicted in this chapter. Chapter 2 : Objectives, Result and Discussion This chapter deals with the objectives, results and discussions, which is divided into 6 sections. 2.1 Stereoselective reaction of 2-ylidene acenaphthylenones with benzylidene succinimides In this section, we depicted the studies of [3+2] cycloaddition reaction between alkylidene acenaphthylenones and arylidene-1-phenyl succinimides under base catalysis to generate succinimide substituted spiro[acenaphthylenone-cyclopentane]fused frameworks in a highly regio- and stereoselective manner under mild conditions. The protocol is highly efficient and furnishes products via two consecutive C–C bond formation. The metal-free approach afforded the spiro-cyclized products in good to excellent yield and the main advantage of the protocol was that it did not need any column chromatography. 2.2 Regeoselective reaction of 2-ylidene acenaphthylenones with 1,4-benzoxazinones This section deals with the formation of polyheterocyclic compounds integrated with pyrrole moiety from the reaction between alkylidene acenaphthylenones with benzoxazinones via [3 + 2] cycloaddition reaction. The reaction made use of environmentally benign iodine catalyst and the corrensponding products were obtained in very high yields with a plethora of functional group regioselectivity. Pyrrole ring is found incorporated in many natural compounds. Polypyrrolo compounds were isolated by simple filteration obviating tedious column chromatography technique. 2.3 Regioselective reaction of 2-substituted-2-hydroxy-indane-1,3-diones with 1,4-benzoxazinones This section deals with the formation of polyheterocyclic compounds having pyrrole unit in their core structure. The reaction proceeded via [3 + 2] cycloaddition reaction between 2-substituted-2-hydroxy indane-1,3-diones and benzoxazinones. The protocol involved in the formation of C–C and C–N bonds through a domino reaction. The reaction was facilitated by the use of Lewis-acid catalyst affording the products in good to excellent yield with high functional group tolerance. The products were obtained by simple filtration and washing with methanol and did not need any purification techniques like column chromatography and recrystallization.2.4 Stereoselective reaction of 2-substituted-2-hydroxy-indane-1,3-diones with benzylidene succinimides In this section, the formation of polycyclic compounds via the reaction of 2-substituted-2-hydroxy indane-1,3-diones and arylidene succinimides was detailed. The reaction involes [3 + 2] cycloaddition reaction affording the spirocyclized product in good yield. The reaction proceeded smoothly with good substrate scope. This mild and metal-free approach afforded functionally-rich products of medicinal interest with complete regioselectivity and excellent diastereoselectivity. 2.5 Stereoselective reaction of unsaturated pyrazolones with benzylidene succinimides This protocol deals with the synthesis of Michael adduct constituting pyrrolidine and pyrazole ring incorporated in the structure. The reaction happened between unsaturated pyrazolones and arylidene succinimides. The pure products were islolated by column chromatography in good yield. The protocol utilized easily accessible starting materials and reaction proceeded smoothly with good substrate scope. 2.6 Addition-elimination reactions of thiols and amines with acenaphthylenone-derived nitroolefins The protocol is envisioned for the synthesis of vinyl amines and sulfides by the reaction of acenaphthaquinone-based nitroolefins with thiols and aromatic amines. The reaction occurred in two steps; firstly, addition of nucleophile on nitroolefin followed by elimination of HNO2 affording the Abstract corresponding vinyl amines/sulfides in excellent yield. The protocol is highly efficient as the products were isolated by simple filtration without column chromatography. The reaction proceeded rapidly and the products were obtained within few minutes. The main advantage of this rapid protocol was that it was metal-free and catalyst-free and reaction proceeded in methanol solvent. Chapter 3: Experimental The third chapter details the method for the preparation of compounds. In the chapter, all synthesized compounds are characterized by physical and spectroscopic data such as MP, IR, 1H NMR, 13C NMR, Two-Dimensional NMR and mass spectral data.