Synthesis of enantiopure phthalides including 3-butylphthalide, a fragrance component of celery oil, and determination of their absolute configurations.

Enantiopure phthalides 2 and 5-8 were synthesized via enantioresolution of the corresponding alcohols with a chiral auxiliary of camphorsultam dichlorophthalic acid, (1S,2R,4R)-(-)-CSDP acid 3, followed by solvolysis with KOH in MeOH and the catalytic oxidation of chiral glycols with iridium complex 28. The absolute configurations of phthalides 2 and 5-8 were determined by applying the (1)H-NMR anisotropy method of MalphaNP acid (4), 2-methoxy-2-(1-naphthyl)propionic acid, to the chiral synthetic precursory alcohols. In the case of 3-phenylphthalide (R)-(-)-7, the absolute configuration determined by the (1)H-NMR anisotropy method using MalphaNP acid 4 agreed with that by the X-ray crystallographic method. By applying these methods, 3-butylphthalide (S)-(-)-2, a fragrance component of essential oil of celery, has been synthesized in an enantiopure form, and its absolute configuration was unambiguously determined.

The effects of aromatic substituents on the chromatographic enantioseparation of diarylmethyl esters with the whelk-O1 chiral stationary phase.

Members of a series of diarylmethanols, diarylmethyl pivalates, and diarylmethyl acetates (analyte sets 1-26) were enantioresolved with the (S,S)-Whelk-O1 chiral stationary phase (CSP). An analogue of the (S,S)-Whelk-O1 selector was combined with enantioenriched samples of the various diarylmethyl pivalates and thereby used as a chiral solvating agent (CSA) for high field 1H NMR studies. The absolute configurations of a number of chiral diarylmethyl pivalates were assigned using this approach, and hydrolysis of the pivalates allowed assignment of the absolute configurations of the corresponding diarylmethanols. Chromatographic, 1H NMR, and X-ray evidence are given in support of a chiral recognition model for the enantioresolution of diarylmethyl esters on this CSP.

Enantioresolution of fluorinated diphenylmethanols and determination of their absolute configurations by X-Ray crystallographic and 1H NMR anisotropy methods.

Various fluorinated diphenylmethanols were enantioresolved by the methods of chiral camphorsultam-dichlorophthalic acid (CSDP acid) and/or 2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP acid) yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X-ray crystallography of CSDP esters and/or by the (1)H NMR anisotropy method of MalphaNP esters for the first time.

Enantioresolution and absolute configurations of chiral meta-substituted diphenylmethanols as determined by X-ray crystallographic and 1H NMR anisotropy methods.

meta-Substituted diphenylmethanols were enantioresolved by the method of chiral phthalic acid yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X-ray crystallography of chiral phthalate esters and/or by the (1)H NMR anisotropy method using 2-methoxy-2-(1-naphthyl)propionic acid.

Comparison of CD spectra of (2-methylphenyl)- and (2,6-dimethylphenyl)-phenylmethanols leads to erroneous absolute configurations.

Enantiopure (2,6-dimethylphenyl)phenylmethanol (+)-(3) and analog (+)-(4) were prepared and their CD spectra were found opposite to that of (2-methylphenyl)phenylmethanol (R)-(-)-(2), the absolute configuration of which was previously established by X-ray crystallography. Therefore the S absolute configuration was once assigned to (+)-3 and (+)-4. After that we have succeeded in the X-ray analyses of chiral dichlorophthalate esters of (+)-3 and (+)4, which clearly indicated R absolute configuration. It is thus evident that comparison of the CD spectra of alcohols 2, 3, and 4 leads to erroneous absolute configurations.