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

Abstract

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.

Attempts to separate (–)‐α‐thujone, (+)‐β‐thujone epimers from camphor enantiomers by enantioselective HPLC with polarimetric detection

“…It is well documented in the literature that these CSPs are also outstanding chromatographic supports to separate compounds, which are not enantiomers . As an example, the eight stereoisomers issuing from the three stereocentres in 5‐amino‐1,3,5‐triphenyl‐pentane‐1,3‐diol have been baseline separated in a single step . In the case of a pair of enantiomers, the ratio of the peak areas directly provides the enantiomeric ratio without the need for further calibration, whereas in other cases a calibration is required for quantification, as in classical HPLC.…”

Efficient and Regioselective Synthesis of 5-Hydroxy-2-isoxazolines: Versatile Synthons for Isoxazoles, β-Lactams, and γ-Amino Alcohols

“…To develop the approach, our initial efforts were directed toward the synthesis of racemic amino alcohol using 6a as a model substrate. When 4.0 equiv of BH 3 ·THF was used, we observed that the conversion to the desired product 3-amino-3-phenylpropan-1-ol 2a was of 91% yield (Scheme ) . Similarly, products 2b and 2c were also isolated in good yields under the same conditions. , …”

Synthesis, chiral separation, and absolute configuration of bis‐(N‐aryl) atropisomeric triads: 1,2‐Bis‐[4‐methyl‐2‐(thi)oxo‐2,3‐dihydrothiazol‐3‐yl]‐benzene

“…In such a case, the use of chromatography on chiral support with polarimetric detection is an excellent option. [56][57][58] Having determined the chromatographic conditions and sign of first and second eluted enantiomers for each pair in rac-1, rac-2, and rac-3, it was quite easy to select the right chromatographic system to show that starting from enantiopure (1)aS,aS-1, (1)-2 and (1)-3 were obtained (Scheme 4). Chiralcel OB-H was the only column able to separate the enantiomers of the Compounds 1, 2, and 3 in the same run.…”