Research Projects

The proposed research aims to develop a novel catalytic platform for the enantioselective construction of C(sp³)–heteroatom bonds, particularly C(sp³)–N and C(sp³)–S bonds, which are key linkages in a wide range of bioactive molecules and pharmaceuticals. The central innovation of the project lies in harnessing readily available alkyl boronic pinacol esters (alkyl Bpins) in a copper-catalyzed, amino radical transfer (ART) strategy to achieve enantioselective C(sp³)–heteroatom bond formation under mild, photocatalyst-free conditions. Chiral alkyl amines and thiol-containing molecules are highly privileged motifs in drug discovery and chemical biology, yet current methods for their asymmetric synthesis from simple precursors remain limited. This project addresses a key gap in the field: the enantioselective functionalization of C(sp³) centers via radical intermediates, a domain where traditional cross-coupling faces limitations such as slow transmetalation, β-hydride elimination, and protodeborylation, especially with non-activated alkyl boron pinacol esters. The proposed strategy is based on our recently developed strategy, which involves: i) generation of aminyl radicals from redox-active dialkyl aminobenzoates; ii) amino radical transfer (ART) activation of alkyl Bpins to form prochiral or achiral alkyl radicals; and iii) capture of these radicals by a chiral copper catalyst, followed by enantioselective C(sp³)–N or C(sp³)–S bond formation with heteronucleophiles such as sulfonamides, carboxylic amides, or sulfenamides. This radical-based enantioconvergent strategy opens a new frontier in asymmetric catalysis by enabling direct access to three-dimensional, drug-like chemical space, which is increasingly recognized as critical for improving the success rates of clinical drug candidates. The successful development of this methodology will offer a modular and general synthetic platform for accessing a variety of chiral heteroatom-containing motifs, including: a) chiral alkyl amine derivatives, b) chiral thiols, sulfilimines, and sulfoximines, and iii) β-Amino-γ-lactams and other medicinally relevant scaffolds. The synthesis of chiral pharmacophores, enabling late-stage functionalization and structural diversification of drug-like molecules bearing α-chiral amines and thiols, will address a critical scientific and societal need by advancing modern therapeutic development. The innovative nature of the chemistry is expected to stimulate broad interest within the scientific and pharmaceutical community, fostering deeper mechanistic understanding, further discovery, applications in medicinal chemistry, and collaborative opportunities. Participation in these projects will equip students with advanced skills in synthetic methodology, catalysis, ligand design, and mechanistic studies. This research is poised to produce high-impact publications, drive translational outcomes, and strengthen India’s expertise in API synthesis through advances in modern synthetic chemistry.