Starting from 2,4,6-triphenylpyrylium perchlorate, 5-amino-1,3,5-triphenyl-pentane-1,3-diol stereoisomers 4 were obtained in a simple two-step synthesis: reaction with hydroxylamine, and reduction with LAH of the resulting 2-isoxazoline ketone derivative 2. The eight stereoisomers of 4 were separated in a single shot on a chiral stationary phase cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD-H). The absolute configuration of the title compounds, intermediate 2-isoxazoline ketone 2 and isoxazoline alcohol derivative 3 were determined using a combination of diastereoselective synthesis, affiliation of the sign in chemical interconversion method, and X-ray determination. 2-Isoxazoline ketone 2 enantiomers and isoxazoline alcohol 3 enantiomers were obtained by chiral HPLC on Chiralpak AD column. 2-Isoxazoline ketone 2 enantiomers can be racemized via a retro Michael addition.
Copyright 2004 Wiley-Liss, Inc.