Research Projects

Asymmetric synthesis has received worldwide interest due to the increasing demand for optically pure chiral compounds in pharmaceuticals, agrochemicals, natural products, and materials science. In this context, tremendous progress has been achieved over the past two decades towards the synthesis of enantiomerically enriched chiral molecules with central, axial, planar, and helically chirality. Against this backdrop, there has been limited advancement in the catalytic enantioselective synthesis of heteroatom stereogenic compounds. In this context, the development of new synthetic methodologies to access heteroatom stereogenicity by utilizing N-heterocyclic carbene (NHC) organocatalysis appears interesting and would likely open new avenues for asymmetric catalysis under metal-free, and possibly mild conditions. This proposal envisions extending NHC organocatalysis beyond its well-established applications in the synthesis of centrally and axially chiral molecules. The focus will be directed toward achieving stereocontrol at heteroatoms, specifically sulfur, phosphorus, silicon, and germanium. Only a limited number of studies have demonstrated the enantioselective synthesis of S-, P-, and Si-stereogenic compounds via NHC catalysis, and notably, there are no reports to date on the asymmetric synthesis of molecules bearing a germanium stereocenter. This work thus aims to address this significant gap and pioneer new frontiers in asymmetric organocatalysis. As part of this effort, we have designed a series of strategic transformations, including the NHC-catalyzed kinetic resolution of N-aryl sulfinamides and the dynamic kinetic resolution of dialdehydes, aimed at the construction of molecules bearing sulfur-centered stereogenicity. Moreover, NHC-catalyzed desymmetrization of diazaphosphepine oxides, methyl divinylphosphine oxide and dearomative amination strategy has been envisioned to access the molecule bearing ‘P’ stereogenic center. Additionally, NHC-catalyzed (3+3) annulation strategy was envisioned to deliver ‘P’ stereogenic center with point chirality. We also plan the NHC-catalyzed Stetter reaction and acylation strategy to access various heterocycles bearing Si stereogenic centers. Notably, we also propose the first NHC-catalyzed desymmetrization strategy for the enantioselective construction of Ge-stereogenic centers. Moreover, the kinetic resolution strategy for the synthesis two FDA approved drugs such as (R)-cyclophosphamide and Esomeprazole has been envisioned in this proposal.