Synthesis and absolute configuration assignment of 5-amino-1,3,5-triphenyl-pentane-1,3-diol stereoisomers

• Published in: Chirality (New York, N.Y.) Vol. 17; no. 1; pp. 63 - 72
• Main Authors: Uncuta, Cornelia, Caraman, George B., Tanase, Catalin I., Bartha, Emeric, Kravtsov, Victor CH, Simonov, Yurii A., Lipkowski, Janus, Vanthuyne, Nicolas, Roussel, Christian
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2005; Wiley
• Subjects: absolute configuration determination; chemical correlation method; Chemical Sciences; chiral HPLC; Chromatography, High Pressure Liquid; configurational diversity; Crystallography, X-Ray; diastereoselective; Glycols - chemistry; isoxazoline reduction; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Stereoisomerism
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.20098

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. Chirality 17:63–72, 2005. © 2004 Wiley‐Liss, Inc.