fluoroketones

Fluoroketones are ketones in which one or more fluorine atoms are directly incorporated into the molecule. The most common motifs are alpha-fluoroketones, where fluorine is on the carbon adjacent to the carbonyl group (R-CHF-CO-R'), and trifluoromethyl ketones, where a CF3 substituent is attached to the alpha carbon (R-CO-CF3). Fluoroketones can also bear several fluorine atoms in other positions, giving rise to difluoro- or polyfluoro-ketones.

Fluorine's strong electronegativity withdraws electron density from the carbonyl, generally increasing the carbonyl's electrophilicity and influencing the acidity of adjacent protons. Fluorination often enhances metabolic stability and lipophilicity, making fluoroketones attractive motifs in medicinal chemistry. The presence of fluorine also provides characteristic signals in 19F NMR, aiding structural analysis and purity assessment.

Synthesis methods for fluoroketones fall into two broad categories. Alpha-fluorination of ketones introduces a fluorine atom onto the alpha carbon using electrophilic fluorinating reagents such as Selectfluor or NFSI, yielding alpha-fluoroketones. Trifluoromethyl ketones form when a CF3 group is installed onto the alpha position or onto a ketone precursor using difluoromethyl or CF3 sources (for example, difluorocarbene reagents or Ruppert–Prakash-type protocols). Other routes include oxidative or catalytic transformations that install fluorinated moieties onto preformed carbonyl compounds.

Applications of fluoroketones span organic synthesis and medicinal chemistry. They serve as versatile intermediates for nucleophilic additions to the carbonyl, as precursors to other fluorinated motifs, and as building blocks in the development of pharmaceuticals and agrochemicals. Their fluorinated character can improve potency, selectivity, and metabolic stability while enabling access to diverse fluorinated frameworks.