Copper-Mediated Deacetylative Fluorination of Methyl Ketones to Alkyl Fluorides

Keywords

alkyl fluorides - copper catalysis - deacetylative fluorination - methyl ketones

Significance

A copper-mediated protocol for the deacetylative fluorination of readily available methyl ketones to alkyl fluorides is disclosed. The ketones are pre-activated by condensation with an N-alkyl hydrazonamide. This method features broad functional group tolerance, allowing for late-stage functionalization and the degree-controlled synthesis of α-mono-, di-, and trifluoroalkanes starting from a single ketone.

 

MissingLinkText

Comment

Various control experiments and DFT calculations support the shown mechanism. It is noteworthy that the fluorine atom transfer occurs with primary alkyl substrates, whereas an S_N2 process via an alkyl–copper(III) intermediate is more likely with secondary alkyl substrates under slightly more forcing conditions (see dashed box).

 

MissingLinkText

 

MissingLinkText

Publication History

Article published online:
27 August 2025