The Enantioselective Organocatalytic 1,4-Addition of Electron-Rich Benzenes to α,β-Unsaturated Aldehydes
The first enantioselective organocatalytic alkylation of electron-rich benzene rings with α,β-unsaturated aldehydes has been accomplished. The use of iminium catalysis has provided a new strategy for the enantioselective construction of benzylic stereogenicity, an important chiral synthon for natural product and medicinal agent synthesis. The (2S,5S)-5-benzyl-2-tert-butylimidazolidinone amine catalyst has been found to mediate the conjugate addition of a wide variety of substituted and unsubstituted anilines to unsaturated aldehydes. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. While catalyst quantities of 10 mol % were generally employed in this study, successful alkylations conducted with catalyst loadings as low as 1 mol % are described.
Additional Information© 2002 American Chemical Society. Received 20 February 2002. Published online 12 June 2002. Published in print 1 July 2002. Financial support was provided by AstraZeneca, GlaxoSmithKline, Johnson and Johnson, Materia, Merck Research Laboratories, Research Corporation (Cottrell Scholarship) and Roche Biosciences. We also thank Great Lakes for their generous donation of amino acids.
Supplemental Material - ja025981p_s1.pdf