Solvent-controlled difluoromethylation of 2′-hydroxychalcones for divergent synthesis of 2′-difluoromethoxychalcones and 2,2-difluoro-3-styryl-2,3-dihydrobenzofuran-3-ols

•Solvent-controlled difluoromethylation of 2′-hydroxychalcones is developed.•The difluoromethyl ethers are obtained with 47–97% yields in p-xylene.•The difluorinated cyclic ethers are obtained with 21–75% yields in acetonitrile.•Difluorocarbene forms two chemical bonds between phenol O and carbonyl C.

The solvent-controlled difluoromethylation of 2′-hydroxychalcones using the shelf-stable reagent difluoromethylene phosphabetaine for divergent synthesis of 2′-difluoromethoxychalcones and 2,2-difluoro-3-styryl-2,3-dihydrobenzofuran-3-ols is developed. When difluoromethylation was performed in p-xylene, 2′-difluoromethoxychalcones were the major product with 47–97% yields, while 2,2-difluoro-3-styryl-2,3-dihydrobenzofuran-3-ols were obtained in 21–75% yields using acetonitrile as solvent. A plausible reaction mechanism was proposed according to the experimental results.

Graphical abstractThe solvent-controlled difluoromethylation of 2′-hydroxychalcones using the shelf-stable reagent difluoromethylene phosphabetaine for divergent synthesis of 2′-difluoromethoxychalcones and 2,2-difluoro-3-styryl-2,3-dihydrobenzofuran-3-ols is developed. When difluoromethylation was performed in p-xylene, 2′-difluoromethoxychalcones were the major product with 47–97% yields, while 2,2-difluoro-3-styryl-2,3-dihydrobenzofuran-3-ols were obtained in 21–75% yields using acetonitrile as solvent.Figure optionsDownload full-size imageDownload as PowerPoint slide