Abstract
The difluoromethyl group (CF(2)H) has garnered significant interest in medicinal chemistry owing to its unique biochemical and physicochemical properties. Its deuterated counterpart (CF(2)D), building on the established utility of CF(2)H, exhibits multifaceted potential for advancing biomedical research and therapeutic development. While the incorporation of the difluoromethyl group (CF(2)H) into drug molecules has matured, efficient installation of its deuterated counterpart (CF(2)D) remains a formidable challenge in medicinal chemistry. This study reports a novel (deuterio)difluoromethyl imidazolate reagent IMDN-SO(2)CF(2)X (X = D, H), which is used to successfully construct various highly selective (deuterio)difluoromethyl compounds in the form of (deuterio)difluoromethyl radicals while maintaining high deuteration rates, achieving >99% isotopic purity in deuterium incorporation. The reagent enables precise CF(2)D and CF(2)H installation in natural products and synthetic bioactive compounds, showing broad substrate compatibility. This establishes a robust deuteration platform for drug discovery.