Year: 2024
Type: preprint
Abstract: Given the prevalence of nitrogen-containing heterocycles in FDA-approved drugs, selectively incorporating a single nitrogen atom emerges as a promising scaffold-hopping approach to enhance chemical diversity in drug discovery libraries. In this study, we harness the distinct reactivity of sulfenylnitrenes, which insert a single nitrogen atom to transform readily available pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, and triazines, respectively. Our additive-free method for skeletal editing employs easily accessible, benchtop-stable sulfenylnitrene precursors over a broad temperature range (–30 to 150 ºC). This chemical approach is compatible with diverse functional groups, including oxidation-sensitive functionalities like phenols and thioethers, and has been applied to various natural products, amino acids, and pharmaceuticals. Furthermore, we have conducted mechanistic studies and explored regioselectivity outcomes through DFT calculations.
Source: ChemRxiv
Institution: University of Oklahoma
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4402883099