Enantioselective Organocatalytic α-Fluorination of Aldehydes
The first direct enantioselective catalytic α-fluorination of aldehydes has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective fluorination of aldehydes to generate α-fluoro aldehydes, an important chiral synthon for medicinal agent synthesis. The use of imidazolidinone 1 as the asymmetric catalyst has been found to mediate the fluorination of a large variety of aldehyde substrates with N-fluorobenzenesulfonimide serving as the electrophilic source of fluorine. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. While catalyst quantities of 20 mol % were generally employed in this study, successful halogenation can be accomplished using catalyst loadings as low as 2.5 mol %.
Additional Information© 2005 American Chemical Society. Received March 21, 2005. Publication Date (Web): May 19, 2005. Financial support was provided by the NIHGMS (R01 GM66142-01) and kind gifts from Amgen and Merck. Mike Brochu is thanked for experimental efforts.
Supplemental Material - ja051805fsi20050421_051112.pdf