Chlorodifluoromethyl aryl ketones and sulfones as difluorocarbene reagents: The substituent effect

We have investigated the different chlorodifluoromethyl aryl ketones 1a–1g and sulfones 2a–2h as difluorocarbene reagents for O- and N-difluoromethylations. It was found that the sulfone reagents 2 were generally more efficient in difluoromethylation than the ketone reagents 1. Furthermore, while the different substituents on ketone reagents 1 did not show a remarkable impact on the difluoromethylation reaction, the substituent effect on the sulfone reagents 2 was much more significant. Finally, we found that p-chlorophenyl chlorodifluoromethyl sulfone 2d and p-nitrophenyl chlorodifluoromethyl sulfone 2h were among the most powerful difluorocarbene reagents in this category for O-difluoromethylations.

Graphical abstractThis paper describes the interesting substitution effect in chlorodifluoromethyl aryl ketones and sulfones as difluoromethylating agents for phenols. It was found that, while the different substitution groups on ketone reagents 1 did not show a remarkable impact on the difluoromethylation reaction, the substitution effect on the sulfone reagents 2 was much more significant. Finally, we figured out that p-chlorophenyl chlorodifluoromethyl sulfone 2d and p-nitrophenyl chlorodifluoromethyl sulfone 2h were among the most powerful difluorocarbene reagents in this category.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Chlorodifluoromethyl aryl ketones 1 and sulfones 2 were surveyed as:CF2 reagents. ► The substitution groups on reagents 1 and 2 showed different effect on their reactivity. ► Two of the most efficient difluorocarbene reagents in this category have been selected. ► The different substitution effects on 1 and 2 were rationalized.