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-aminooxetan es cis-5 and cis-7 is reported. The oxetanes were obtained by the photocycl oaddition of aliphatic (6c-e) and aromatic (4, 6a) aldehydes to the corresp onding enamides (1a-d,h) or enecarbamates (le-g). The enamine derivatives u sed in the Paterno-Buchi reaction were either commercially available or pre pared from the corresponding acetaldehyde imines 2 by acylation. The oxetan e formation proceeded with good-to-excellent simple diastereoselectivity fo r aromatic aldehydes (56-82% yield) and moderate selectivity for aliphatic aldehydes (46-55% yield). The cis-3-aminooxetanes are precursors for syn- a nd anti-1,2-amino alcohols. The relative configuration established in the p hotochemical step was retained upon nucleophilic ring opening between the o xygen 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-5e and cis-5f were transformed into anti-1,2-amino alcohols. Upon treatment with trifluoroacetic acid, they underwent an intr amolecular nucleophilic substitution at the carbon atom C-2 of the oxetane and the oxazolidinones II and 12 were formed. Because the substitution occu rs with inversion of configuration, anti-1,2-amino alcohols, e.g., ephedrin e (15), are accessible.