A new, mild, and efficient synthesis of 2,2-difluoro-3-hydroxyacids through a selective haloform reaction.
[reaction: see text] Long-chain 2,2-difluoro-3-hydroxyacids have been synthesized in a new, straightforward manner by treatment of 4-hydroxy-1,1,1,3,3-pentafluoroalkyl ketones, easily obtained by reaction of pentafluoroenolate 2 with aldehydes and ketones, with base under mild conditions. The reaction sequence is marked by the selective cleavage of the CO-CF3 bond, as well as the absence of products arising from the alternative CO-CF2R bond cleavage. The process represents a convenient approach for the synthesis of 2,2-difluoro-3-hydroxyacids, as it is short, provides good to excellent yields under mild conditions, and uses hexafluoro-2-propanol, a very cheap reagent, as the fluorine source.
Jiménez
O
O
Barcelona Science Parc, University of Barcelona, Josep Samitier 1-5, 08028-Barcelona, Spain.
Bosch
M P
MP
Guerrero
A
A