Photocycloaddition of N-Acyl Enamines to Aldehydes and Its Application to the Synthesis of Diastereomerically Pure 1,2-Amino Alcohols

The regio- and stereoselective synthesis of the protected cis -3-aminooxetanes cis - 5 and cis - 7 is reported. The oxetanes were obtained by the photocycloaddition of aliphatic ( 6c − e ) and aromatic ( 4, 6a ) aldehydes to the corresponding enamides ( 1a − d, h ) or enecarbamates ( 1e − g ). The enamine derivatives used in the Paternò−Büchi reaction were either commercially available or prepared from the corresponding acetaldehyde imines 2 by acylation. The oxetane formation proceeded with good-to-excellent simple diastereoselectivity for aromatic aldehydes (56−82% yield) and moderate selectivity for aliphatic aldehydes (46−55% yield). The cis -3-aminooxetanes are precursors for syn - and anti -1,2-amino alcohols. The relative configuration established in the photochemical step was retained upon nucleophilic ring opening between the oxygen atom and carbon atom C-4. By this means, syn -1,2-amino alcohols such as 8 and 10 were available in good yields. In contrast, the N -Boc-protected cis -3-aminooxetanes cis - 5 e and cis - 5 f were transformed into anti -1,2-amino alcohols. Upon treatment with trifluoroacetic acid, they underwent an intramolecular nucleophilic substitution at the carbon atom C-2 of the oxetane and the oxazolidinones 11 and 12 were formed. Because the substitution occurs with inversion of configuration, anti -1,2-amino alcohols, e.g., ephedrine ( 15 ), are accessible.