Programmable synthesis of difluorinated hydrocarbons from alkenes through a photocatalytic linchpin strategy

The introduction of difluoromethylene moieties into organic molecules has garnered significant attention due to their profound influence on the physicochemical and biological properties of compounds. Nonetheless, the existing approaches for accessing difluoroalkanes from readily available feedstock chemicals remain limited. In this study, we present an efficient and modular protocol for the synthesis of difluorinated compounds from alkenes, employing the readily accessible reagent, ClCF2SO2Na, as a versatile difluoromethylene linchpin. By means of an organophotoredox-catalysed hydrochlorodifluoromethylation of alkenes, followed by a ligated boryl radical-facilitated halogen atom transfer (XAT) process, we have successfully obtained various difluorinated compounds, including gem-difluoroalkanes, gem-difluoroalkenes, difluoromethyl alkanes, and difluoromethyl alkenes, with satisfactory yields. The practical utility of this linchpin strategy has been demonstrated through the successful preparation of CF2-linked derivatives of complex drugs and natural products. This method opens up new avenues for the synthesis of structurally diverse difluorinated hydrocarbons and highlights the utility of ligated boryl radicals in organofluorine chemistry. We have devised a general and versatile approach for the synthesis of diverse difluorinated alkanes and alkenes by utilizing readily accessible ClCF2SO2Na as a practical difluoromethylene linchpin.

Automated summary

This study presents an efficient and modular protocol for synthesizing difluorinated compounds using readily accessible ClCF2SO2Na as a versatile difluoromethylene linchpin. Various difluorinated compounds were successfully obtained with satisfactory yields, including gem-difluoroalkanes, gem-difluoroalkenes, difluoromethyl alkanes, and difluoromethyl alkenes. The practical utility of this method was demonstrated through the successful preparation of CF2-linked derivatives of complex drugs and natural products. This method opens up new avenues for synthesizing structurally diverse difluorinated hydrocarbons and highlights the utility of ligated boryl radicals in organofluorine chemistry.