deoxyfluorination

Deoxyfluorination is a class of reactions that replaces an oxygen substituent in an organic molecule with fluorine. The term covers both the conversion of alcohols or their derivatives into alkyl fluorides and the conversion of carbonyl groups (aldehydes and ketones) into difluoromethyl motifs. In practice, deoxyfluorination enables the introduction of fluorine by removing an oxygen atom and installing fluorine in its place, often with retention or inversion of configuration depending on the substrate and mechanism.

Most widely used reagents are sulfur(VI) fluoride reagents such as diethylaminosulfur trifluoride (DAST) and Deoxo-Fluor, as well as more recent reagents designed to improve safety and scope. Alcohols react by forming a reactive alkoxysulfuryl intermediate or related leaving groups, which are displaced by fluoride to give alkyl fluorides. For carbonyl substrates, these reagents enable difluorination of C=O bonds, delivering gem-difluoro motifs in the product. Reactions can proceed under mild to moderate conditions but are moisture sensitive and may generate hazardous byproducts.

Substrates include primary, secondary, and tertiary alcohols, as well as benzylic, allylic, and aliphatic examples. Functional groups that survive fluoride are generally tolerated; however, sterically hindered alcohols and sensitive functionalities may pose challenges. Side reactions include elimination, rearrangement, and over-fluorination. Safety concerns: many deoxyfluorination reagents are moisture sensitive and can be exothermically unstable or hazardous on scale; proper handling and quenching are essential.

Deoxyfluorination is widely used to prepare organofluorine building blocks for pharmaceuticals and agrochemicals. Classic examples include conversion of benzyl alcohols to benzyl fluorides and carbonyls to difluoromethyl derivatives, with conditions tailored to substrate class and desired product.