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

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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.