Direct and Enantioselective Organocatalytic α-Chlorination of Aldehydes
The first direct enantioselective catalytic α-chlorination of aldehydes has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective chlorination of aldehydes to generate α-chloro aldehydes, an important chiral synthon for chemical and medicinal agent synthesis. The use of imidazolidinone 3 as the asymmetric catalyst has been found to mediate the halogenation of a large variety of aldehyde substrates with the perchlorinated quinone 1 serving as the electrophilic chlorinating reagent. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. The capacity of catalyst 3 to override the inherent bias of resident stereogenicity in the chlorination of enantiopure β-chiral aldehydes is also described. Catalyst quantities of 5 mol % were generally employed in this study.
Additional Information© 2004 American Chemical Society. Received 25 January 2004. Published online 11 March 2004. Published in print 1 April 2004. Financial support was provided by kind gifts from Bristol-Myers Squibb, Eli Lilly, and Merck Research Laboratories. D.W.C.M is grateful for support from the Sloan Foundation and Research Corporation. Teresa Beeson is thanked for additional enantioselectivity analysis.
Supplemental Material - ja049562zsi20040223_021457.pdf