In the Sharma lab, we are investigating the untapped potential of sulfur in regulating and fine-tuning the behavior of carbenes/nitrenes due to its metallomimetic characteristics. Specifically, we are studying a unique class of sulfur-based carbenes and nitrenes, termed sulfenylcarbenes and sulfenylnitrenes, where a sulfur atom in the +2-oxidation state is bonded to a carbene-carbon or nitrene-nitrogen, respectively.

Nitrogen-containing heterocycles are ubiquitous in commercial drugs, making their selective modification a key strategy for expanding chemical diversity in drug discovery libraries. Here, we introduce efficient skeletal editing methods leveraging the unique reactivity of sulfenyl-carbenes/nitrenes to insert single carbon or nitrogen atoms. These transformations enable the conversion of pyrroles, indoles, and imidazoles into challenging scaffolds such as pyridines, pyrimidines, quinolines, quinazolines, and triazines. Notably, sulfenylcarbenes exhibit inverse chemoselectivity compared to conventional carbenes, selectively targeting alkenes while tolerating reactive groups like alcohols, carboxylic acids, and amines. Sulfenylnitrenes, generated thermally across a broad temperature range (–30 to 150 °C), also exhibit remarkable compatibility with diverse functional groups, including oxidation-sensitive functionalities like phenols and thioethers. These versatile methodologies have been applied to complex natural products, amino acids, and pharmaceuticals. Mechanistic insights and regioselectivity outcomes, supported by DFT calculations, highlight the potential of sulfenyl-carbenes/nitrenes for precise molecular framework modification.
Recent Publications:
ChemRxiv, Preprint Available! DOI: 10.26434/chemrxiv-2024-f80wf-v2
ChemRxiv, Preprint Available! DOI: 10.26434/chemrxiv-2024-6dncp