Development of A New Reagent for Ee Determination with High Resolution Based on the Fine Chemistry Designing

1. 由于MTPA结构固有的空间拥挤导致氯（1d）对仲醇的反应性不足，以及两种MTPA异构体之间的化学位移差异（delta - adelta值）非常小，因此用MTPA(1)法测定ee失败的例子很多。为了开发一种在分辨率和反应性上都远远超过MTPA的新试剂，我们重点研究了结构2-9。对这些新候选化合物2c-e-9c-e的三种具有代表性的衍生物进行了合成，但由于其多官能团结构的不稳定性，无法得到7c-e和8c-e衍生物。从得到的二对异构体的^<19>F核磁共振光谱中，发现CFPA衍生物9c-e的δ δ δ值比MTPA衍生物1c-e的δ δ δ值大几倍。CFPA-Cl （9b）的反应活性远高于MTPA-Cl （1b）。为了实际使用CFPA （1b）作为新的ee测定试剂，我们随后尝试制备了9a.3的旋光形式。N-[R(+)- -苯基乙基]苯甲酰甲酰胺依次进行氢氰化和氟化反应，得到具有光学活性的酰胺的非星形混合物，并通过分数重结晶分离。将White法应用于这两种异构体，得到了具有光学活性的酸(+)-9a和(-)-9a，并用草醛氯处理得到了相应的氯化物(+)-9b和(-)-9b。通过对9b与醇和胺反应得到的各种化合物的^<19>F NMR研究，表明CFPA法比传统的MTPA法更有效和实用。

1. Many instances have been reported where ee determination by MTPA (1) method failed because of insufficient reactivity of the chloride (1d) towards secondary alcohols due to inherent steric crowdness of the MTPA structure and because of very small chemical shift differences (DELTAdelta values) between the two MTPA diastreomers. In order to develop for a new reagent far surpassing MTPA in its ability of both resolution and reactivity, we have focused on the structures 2-9. Synthesis of the three representative diastreomers for these new candidates 2c-e-9c-e was attempted, however, the derivatives 7c-e and 8c-e could not be obtained because of the instability associated with the multifunctional carbon structures.2. From the ^<19>F NMR spectra for the disterecomers obtained, it was found the DELTAdelta values for CFPA derivatives 9c-e are several times greater than those for MTPA derivatives 1c-e. Furthermore, the reactivity of CFPA-Cl (9b) was shown to be much higher than that of MTPA-Cl (1b). For the practical use of CFPA (1b) as a new ee determining reagent, we then attempted to prepare the optically active forms of 9a.3. N-[R (+)-alpha-Phenylethyl] benzoylformamide was successively subjected to hydrocyanation and fluorination to give a diasteromeric mixture of the optically active amides, which were separated by fractional recrystallization. Application of the method of White to both isomers gave the optically active acids (+)-9a and (-)-9a, and further, the corresponding chlorides (+)-9b and (-)-9b by treatment with oxalylchloride.4. Through the ^<19>F NMR investigation of the various compounds obtained by reaction of 9b with alcohols and amines, it has been shown that the CFPA method is much mere effective and practical free determination than the conventional MTPA method.