A facile preparation method for α,α-difluoroalkanecarboxylic acids and esters. A formal difluoromethylene insertion to alkanecarboxylic acids using radical reaction

Article abstract of DOI:10.1016/0040-4020(94)01099-L

Various alkyl radicals generated by the photoreaction of a series of Barton esters reacted with 1,1-dichloro-2,2-difluoroethene to give radical adducts as the major product accompanied with self-trapping products. Primary, secondary, tertiary, benzyl, and some unsaturated alkyl radicals as well as those with another functional group such as ether, carbonyl, and azide were applicable. Barton esters of diacids also afford 1:2 adducts with a small amount of 1:1 adducts and bis-self-trapping products except for the succinic case. These adducts were hydrolyzed with AgNO₃/H₂O-THF to α,α-difluoroalkanecarboxylic acids and methanolyzed with AgNO₃/MeOH to the corresponding methyl esters. 4-Azido-2,2-difluorobutylic acid and the methyl ester were converted to difluoro-GABA and difluoro-γ-lactams.