Absolute configuration enantioresolution

We have recently developed chiral carboxylic acids as novel molecular tools useful for enantioresolution and simultaneous determination of the absolute configuration of various alcohols. These chiral molecular tools are very powerful for the facile preparation of enantiomers with 100% ee and also for the absolute configurational assignment. Methods using these chiral tools have been successfully applied to various compounds, and their methodologies and applications are explained throughout this chapter. 

Fig. 9.1 Enantioresolution and determination of absolute configuration of alcohols using chiral carboxylic acids [5-8],...

Enantioresolution of Alcohols by HPLC and Simultaneous Determination of Their Absolute Configurations by X-ray Crystallography... 

Table 9.2 Enantioresolution of alcohols by HPLC on silica gel using (lS,2/ ,4R)-(-)-CSDP acid 1, and determination of their absolute configurations by X-ray crystal lography.]...

Various fluorinated diphenylmethanols 36-39 were also enantioresolved as CSDP esters (entries 23-26). In the case of alcohols 36, 37, and 39, their absolute configurations were determined by X-ray crystallography. To those fluorinated alcohols, the method of MaNP acid 3 could be applied for enantioresolution and also for determination of their absolute configurations by the H NMR anisotropy method, as discussed below. Meto-substituted diphenylmethanols 40 and 41 were enantioresolved by the CSDP acid method yielding enantiopure alcohols, the abso-... 

We have discovered that this novel carboxylic acid, MaNP acid 3, is also effective for enantioresolution and simultaneous determination of the absolute configuration of various secondary alcohols by the H NMR anisotropy method [41-52, 56-58]. The results obtained by the H NMR anisotropy mefhod are, of course, consistent wifh those by the X-ray method. Therefore, the methods of CSDP and MaNP acids are useful as complementary molecular tools, as discussed in fhis chapter. 

Fig. 9.16 Enantioresolution of racemic alcohol as (S)-MaNP esters, and determination of the absolute configuration of the first-eluted fraction by the NMR anisotropy method [38, 45, 50],...

We have developed some chiral carboxylic acids as novel molecular tools useful for both enantioresolution of various alcohols and simultaneous determination of their ACs (Figure 55.1). These chiral molecular tools are powerful for facile preparation of chiral compounds with 100% ee and for the absolute configurational assignment. The so-called asymmetric syntheses are useful for preparation of chiral compounds, but reaction products are not always enantiopure, and in some cases, it is necessary to determine their ACs by independent chemical and/or physical methods. The methodologies explained in this chapter are useful for preparation of enantiopure authentic sample and for determination of their ACs in an unambiguous manner. The protocols using these chiral reagents have been successfully applied to various compounds, and their principle and applications are explained in this chapter. 

Watanabe M, Kuwahara S, Harada N, Koizumi M, Ohkuma T. Enantioresolution by the chiral phthalic acid method absolute configurations of (2-methylphenyl)phenylmethanol and related compounds. Tetrahedron Asymm. 1999 10 2075-2078. 

Naito J, Kosaka M, Sugito T, Watanabe M, Harada N, Pirkle WH. Enantioresolution of fluorinated dipbenyhnetbanols and determination of their absolute configurations by X-ray crystallographic and H NMR anisotropy methods. Chirality 2004 16 22-35. 

Harada N, Watanabe M, Kuwahara S, Sugio A, Kasai Y, Ichikawa A. 2-Methoxy-2-(l-naphthyl)propionic acid, a powerful chiral auxiliary for enantioresolution of alcohols and determination of their absolute configurations by the H NMR anisotropy method. Tetrahedron Asymm. 2000 1 1249-1253. 

Figure 203. Enantioresolution and assignment of the absolute configuration of the enantiomers of a chiral secondary alcohol by tamden HPLC NMR of its (i )-9-AMA esters (the assignment is the opposite if (5)-9-AMA is chosen as the reagent).

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