一鍋化多米諾骨牌式轉換合成骨架多樣性異環小分子

Abstract

The recent emergence of multicomponent cascade reactions has provided novel approaches that expand the compendium of methods to assemble libraries of heterocyclic compounds. Tandem reactions are widely employed in organic synthesis due to high atom economy, minimum waste generation, and construction of complex molecules through two or more bond formations in one pot. The present thesis deals with the synthesis of nitrogen heterocycles via domino transformations. The thesis is divided into four chapters for the sake of convenience and better understanding. The first chapter deals with a novel and highly efficient copper catalyzed tandem synthesis of triazolo quinazolinones. The synthetic strategy involves a sequential one-pot click reaction followed by aerobic intramolecular C-H amidation. Two distinct important transformations were carried out in one-pot by employing a single cost effective copper catalyst. The milder, rapid, oxidant and ligand free reaction conditions as well as broader substrate scope are the salient features of this novel protocol. In the second chapter, a novel and highly chemoselective protocol for the construction of thioxoimidazolidinone and aminoimidazolone framework is developed. The influence of reaction conditions on the product outcome was studied thoroughly and established two distinct approach for their selective formation. In such a one-pot reaction, ambient temperature conditions generally resulted in the formation of thioxoimidazolidinones while the microwave irradiation provided aminoimidazolones exclusively. An attempt to elucidate the observed chemoselectivity is described and supported by X-ray studies. One-pot synthesis of marine alkaloid Leucettamine B was achieved based on this novel protocol. The third chapter describes a novel one-pot, three-component reaction employing variously substituted benzimidazole-linked amino pyridines, aldehydes and isonitriles catalyzed by scandium (III) triflate under solvent-free conditions. This new synthetic methodology facilitates the rapid generation of intricate molecular frameworks in three-dimensional fashion leading to benzimidazole-imidazo[1,2-a] pyridines. This approach is envisaged as an environmentally benign process and a simple operation to the biological interesting compounds. The present synthetic sequence permits the introduction of three points of structural diversity to expand chemical space with high purity and excellent yields. The final chapter emphasizes the one-pot, domino synthesis of benzimidazole linked thiazitine derivatives on ionic liquid support. Three component reaction of 2-aminobenzimidazole with isothiocyanates and diidomethane was developed. The reaction sequence involves the formation of thiourea, S-alkylation with diiodomethane followed by ring closing to furnish thiazitines. To incorporate more skeletal diversity, we have demonstrated solution phase synthesis of thiazolidines and selenazolidines using dichloroethane as two carbon electrophile.

The recent emergence of multicomponent cascade reactions has provided novel approaches that expand the compendium of methods to assemble libraries of heterocyclic compounds. Tandem reactions are widely employed in organic synthesis due to high atom economy, minimum waste generation, and construction of complex molecules through two or more bond formations in one pot. The present thesis deals with the synthesis of nitrogen heterocycles via domino transformations. The thesis is divided into four chapters for the sake of convenience and better understanding. The first chapter deals with a novel and highly efficient copper catalyzed tandem synthesis of triazolo quinazolinones. The synthetic strategy involves a sequential one-pot click reaction followed by aerobic intramolecular C-H amidation. Two distinct important transformations were carried out in one-pot by employing a single cost effective copper catalyst. The milder, rapid, oxidant and ligand free reaction conditions as well as broader substrate scope are the salient features of this novel protocol. In the second chapter, a novel and highly chemoselective protocol for the construction of thioxoimidazolidinone and aminoimidazolone framework is developed. The influence of reaction conditions on the product outcome was studied thoroughly and established two distinct approach for their selective formation. In such a one-pot reaction, ambient temperature conditions generally resulted in the formation of thioxoimidazolidinones while the microwave irradiation provided aminoimidazolones exclusively. An attempt to elucidate the observed chemoselectivity is described and supported by X-ray studies. One-pot synthesis of marine alkaloid Leucettamine B was achieved based on this novel protocol. The third chapter describes a novel one-pot, three-component reaction employing variously substituted benzimidazole-linked amino pyridines, aldehydes and isonitriles catalyzed by scandium (III) triflate under solvent-free conditions. This new synthetic methodology facilitates the rapid generation of intricate molecular frameworks in three-dimensional fashion leading to benzimidazole-imidazo[1,2-a] pyridines. This approach is envisaged as an environmentally benign process and a simple operation to the biological interesting compounds. The present synthetic sequence permits the introduction of three points of structural diversity to expand chemical space with high purity and excellent yields. The final chapter emphasizes the one-pot, domino synthesis of benzimidazole linked thiazitine derivatives on ionic liquid support. Three component reaction of 2-aminobenzimidazole with isothiocyanates and diidomethane was developed. The reaction sequence involves the formation of thiourea, S-alkylation with diiodomethane followed by ring closing to furnish thiazitines. To incorporate more skeletal diversity, we have demonstrated solution phase synthesis of thiazolidines and selenazolidines using dichloroethane as two carbon electrophile.