Executive Summary : | The research focuses on developing innovative, catalytic, and pot-economic routes for preparing enantiomerically pure aza-heterocycles with diverse substituents. High-energy 4-membered nitrogen heterocycles, such as azetidines, azetines, and azetidine nitrones, are the structural core found in various bioactive molecules, pharmaceutical agents, and drug molecules. However, asymmetric construction of substituted azetidines nitrones as feed-stock for various transformations is missing in the literature. Traditional protocols only provide access to racemic versions of nitrones, which suffer from limitations such as tedious synthetic routes, costly transition metallic catalysts, unwanted by-products, and harsh reaction conditions. To overcome these difficulties, this proposal aims to develop new catalytic sustainable domino tactics for enantio- and diastereoselective access to high-energy azetidine nitrones and their sophisticated synthetic applications. Organocatalysts have emerged as a powerful toolbox in asymmetric catalysis, capable of efficiently making vital classes of a myriad of stereochemically rich molecules. The proposed project proposes challenging [2+2] cyclization reactions between alkyl-substituted nitroolefins/nitroalkanes/proparglamines and alkyl/arylidene malononitriles/α-alkynyl-β-substituted nitroolefins using suitable catalysts, aiming for various azetidines nitrones with excellent stereoselectivities. The project will focus on developing efficient organocatalytsts for asymmetric [2+2] aza-cyclization reactions involving simple reactants, minimizing catalyst loading, suitable for gram-scale reactions with large substrate scope, easily transmuting synthesized azetidine nitrones into synthetically and biologically promising diverse skeletons, and creating a new catalytic concept for future growth in this area. |