To compare the crystalline-state conformations of MαNP acid esters with those existing in the solution state, X-ray crystallographic analyses of 22 MαNP esters and two MαNP acids were carried out. It was found that all 27 conformers observed in the solid state have structures in which the 2-CH 3 group and the 2Ј-H of the naphthyl group are synperiplanar and are almost always located in the same plane. In addition, the CH 3 -O7-C2-C1 moiety in all cases has an antiperiplanar structure within the MαNP plane. From further analyses, 22 conformers adopt the so-called syn structure, in which the O7-C2-C1-O6 moiety is synperiplanar. On the other hand, the remaining five conformers have the so-called anti structure. With regard to the rotational conformation around C1ЈЈ-O5, all conformers have structures similar to the synperiplanar conformation. In the so-called syn conformers, the interatomic distance d(H8Ј-O6) is distributed between 2.48 Å and 2.96 Å, while the distance d(H8Ј-O7) varies between 2.26 Å and 2.56 Å, indicating the weak bifurcated hydrogen

The MαNP acid method has been applied to racemic aliphatic acetylene alcohols in order to simultaneously prepare enantiopure alcohols and to determine their absolute configurations by 1 H NMR anisotropy. Racemic acetylene alcohols 6-8, 11, and 20 were esterified with MαNP acid (S)-(+)-1 to yield diastereomeric MαNP esters which were efficiently separated by HPLC on silica gel with separation factors α in the range 1.60-1.93. The 1 H NMR anisotropy factors ∆δ [= δ(2nd fr.) -δ(1st fr.)] were calculated from the data of the first-(22a-

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.

Racemic 2-aryl-2-methoxypropionic acids were enantioresolved by the use of (S)-(-)-phenylalaninol 4. For instance, racemic 2-methoxy-2-phenylpropionic acid (+/-)-7 was condensed with phenylalaninol (S)-(-)-4 yielding a diastereomeric mixture of amides, which was easily separated by HPLC on silica gel affording the first-eluted amide (-)-13a and the second-eluted amide (+)-13b: alpha = 3.19, Rs = 3.49. The absolute configuration of amide (-)-13a was determined to be (R;S) by X-ray crystallography by reference to the S configuration of the phenylalaninol moiety. Amide (R;S)-(-)-13a was converted to oxazoline (R;S)-(-)-14a, from which enantiopure 2-methoxy-2-phenylpropionic acid (R)-(-)-7 was recovered. Other 2-aryl-2-methoxypropionic acids, (R)-(-)-8, (R)-(-)-9, (R)-(+)-10, (R)-(-)-11, and (R)-(-)-12, were similarly prepared in enantiopure forms with the use of phenylalaninol (S)-(-)-4, and their absolute configurations were clearly determined by X-ray crystallography or by chemical correlation.

Abstract:The development and