Stereoselective synthesis of (E)-trisubstituted alpha,beta-unsaturated amides and acids.
Potassium alkoxides of N-acyl-oxazolidin-2-one-syn-aldols undergo stereoselective elimination reactions to afford a range of trisubstituted (E)-alpha,beta-unsaturated amides in >95% de, that may be subsequently converted into their corresponding (E)-alpha,beta-unsaturated acids or (E)-alpha,beta-unsaturated oxazolines in good yield. syn-Aldols derived from alpha,beta-unsaturated aldehydes gave their corresponding trisubstituted (E)-alpha,beta-unsaturated-amides with poorer levels of diastereocontrol, whilst there was a similar loss in (E)-selectivity during elimination of syn-aldols derived from chiral aldehydes. These elimination reactions proceed via rearrangement of the potassium alkoxide of the syn-aldol to a 1,3-oxazinane-2,4-dione enolate intermediate that subsequently eliminates carbon dioxide to afford a trisubstituted (E)-alpha,beta-unsaturated amide. The (E)-selectivity observed during the E1cB-type elimination step has been rationalised using a simple conformational model that employs a chair-like transition state to explain the observed stereocontrol.
Feuillet
Fred J P
FJ
Department of Chemistry, University of Bath, BA2 7AY, UK.
Cheeseman
Matt
M
Mahon
Mary F
MF
Bull
Steven D
SD
D000577:Amides / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000138:chemical synthesis*; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis; D013237:Stereoisomerism
D000577:Amides; D002264:Carboxylic Acids; D010080:Oxazoles