Research Projects

Atropisomerism—arising from hindered rotation about single bonds—plays a vital role in the activity and selectivity of numerous biologically active compounds, natural products, and chiral ligands. Developing new catalytic strategies for the enantioselective construction of atropisomers remains a significant challenge in asymmetric synthesis. The current proposal seeks to develop a novel approach that enables remote control of atroposelectivity via organocatalytic activation of alkynes, generating reactive vinylidene para-quinone methide (p-VQM) intermediates in situ. Vinylidene-p-QMs are highly conjugated, reactive species that can mediate cascade cyclization or nucleophilic addition processes, allowing spatial and stereochemical information to be transmitted across molecular frameworks. Despite their synthetic potential, their use in asymmetric catalysis—especially for atroposelective bond formation—is underexplored. This project aims to design and synthesize arylalkyne-tethered precursors that, under the influence of chiral Brønsted bases or hydrogen-bonding organocatalysts, undergo in situ formation of vinylidene p-QMs, followed by stereoselective annulation or bond rotation restriction to furnish axially chiral biaryls or heterocycles. Key aspects of the strategy include: 1. Organocatalytic generation of p-VQM intermediates under mild, metal-free conditions. 2. Remote stereochemical induction, enabling control over axial chirality through catalytic, non-covalent interactions. 3. Exploration of diverse substrate scopes, including enynes, conjugated moiety, and aryl-ketone systems. Mechanistic investigations, including kinetic studies and computational modeling, will help elucidate the reaction pathways and stereo-determining steps. The proposed methodology could open new vistas in atroposelective synthesis and provide access to novel chiral scaffolds relevant to medicinal chemistry and ligand design. Ultimately, this project will contribute to advancing organocatalysis beyond traditional enamine and iminium activation, exploring alkynes as valuable yet underutilized electrophilic partners. It aligns with green chemistry principles and has the potential to yield high-impact publications and inspire future synthetic applications.