Alpha'-hydroxyenones as mechanistic probes and scope-expanding surrogates for alpha,beta-unsaturated aldehydes in N-heterocyclic carbene-catalyzed reactions.
N-heterocyclic carbene-catalyzed reactions of alpha,beta-unsaturated aldehydes and a variety of electrophiles allow the facile preparation of a diverse array of annulation products including trisubstituted cyclopentenes, gamma-lactams, and bicyclic beta-lactams. The substrate scope of these reactions, however, is limited by the difficulties of preparing the starting alpha,beta-unsaturated aldehydes. We now report that alpha'-hydroxyenones, which can be prepared in a single convenient step from aromatic and heteroaromatic aldehydes, can serve as efficient surrogates for enals in the annulation reactions. This protocol allows the facile preparation and use of substrates bearing nitrogen heterocycles. These reagents have also allowed us to demonstrate that, in contrast to other classes of aldehydes, the formation of the Breslow intermediate from enals and N-heterocyclic carbenes is irreversible under the reaction conditions.
Chiang
Pei-Chen
PC
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Rommel
Michael
M
Bode
Jeffrey W
JW
D000438:Alcohols / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry; D002384:Catalysis; D003517:Cyclopentanes / Q000138:chemical synthesis*; D007659:Ketones / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry
D000438:Alcohols; D000447:Aldehydes; D000475:Alkenes; D003517:Cyclopentanes; D007659:Ketones; D007769:Lactams; C030011:carbene; D008697:Methane