Enantioselective Fluoronation With a Simple Organic Catalyst

Key words

fluorination - prolines - N-fluorodibenzene­-sulfonimide

Significance

Fluorinated molecules are very important in medicinal, agricultural and materials science. This report is the first asymmetric fluorination of aldehydes with a simple catalyst obtaining extremely high ee’s. The use of methyl tert-butyl ether as a solvent proved to be critical to reduce difluorination. The use of N-fluorodibenzenesulfonimide (NFSI), which is a commercially available, stable and easy to handle fluoride source, is an excellent complement to the already simple catalyst system. The optically active α-fluorinated aldehydes were directly reduced to the corresponding α-fluorinated alcohols since the α-fluorinated aldehydes are unstable and more volatile than starting materials.

Comment

The authors have shown this proline-derived catalyst to be efficient for fluorination under ideal conditions (low catalyst loading, room temperature) for a variety of substrates. The catalyst is believed to operate through fluorination of the enamine intermediate. The proposed reason for the high yields of mono-fluorinated compounds with high ee’s is rationalized through shielding of the α-proton by the bulky aryl groups, prohibiting racemization. For the same catalyst and asymmetric epoxidation see: J. Am. Chem. Soc. 2005, 127, 6964-6965.