Stereoselective synthesis of (E)-trisubstituted α,β-unsaturated amides and acids

Abstract

Potassium alkoxides of N-acyl-oxazolidin-2-one-syn-aldols undergo stereoselective elimination reactions to afford a range of trisubstituted (E)-α,β-unsaturated amides in >95% de, that may be subsequently converted into their corresponding (E)-α,β-unsaturated acids or (E)-α,β-unsaturated oxazolines in good yield. syn-Aldols derived from α,β-unsaturated aldehydes gave their corresponding trisubstituted (E)-α,β-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)-α,β-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.