Absolute configuration enantiopure compounds

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

Von Zelewsky has published many examples of the stereoselective synthesis of metal complexes using what he refers to as chiragen ligands. These are enantiopure natural compounds synthesized from the natural product (—)-a-pinene, which is combined with species such as bipyridine units to provide impressive control of metal-centered chirality.159-161 In this section, we will focus on the determination of absolute configurations in terms of stereospecific formation from different points of view in connection with absolute conformations in the ligands. 

The CD spectra of enantiopure pyridinophane 17 and bipyridine derivative 18 were reported. Both spectra were relatively complicated compared to those of substituted [2.2]paracyclophanes, apparently showing 6-8 positive/negative Cotton effect peaks. While the lAel value for the main band of compound 18 (20-30 M-1 cm-1) was reduced to half that of compound 17 (30-50 M 1 cm ), the spectrum of planar chiral bipyridine 18 was very sensitive to the added metal salts. The absolute configuration was determined by comparison with the theoretical spectrum at the DFT/SCI level [31]. 

Chiral molecules are characterized by three-dimensional handedness and can exist in two enantiomeric forms of opposite absolute configuration (AC). Most natural products and biologically active compounds are chiral and their biological and molecular functions are closely related to their chirality, that is, AC and conformation. Furthermore, many drugs derived from natural products or of purely synthetic origin are currently used in enantiopure form. Therefore, the unambiguous determination of the AC of chiral compounds is critical for the studies of natural products and biomolecular systems.1... 

Alcohols 19 and 21 are very unique chiral compounds, the chirality of which is generated by the substitution of isotopes in the case of 19, H vs. D in the case of 21, C vs. C, so it is very difficult to recognize such an extremely small chirahty directly. To synthesize enantiopure alcohols 19 and 21, and to determine their absolute configurations, the indirect chemical conversion method was employed as follows. For example, deuterium-substituted/4-Br alcohol 20 was similarly enantioresolved as in the case of compound 14 (entry 9). The enantiopure alcohol (S)-(-)-20 obtained was reduced to remove the Br atom yielding (S)-(-)-19, which exhibits a negative CD Cotton effect at 270.4 nm. In a similar way, C-substituted... 

Although the CSDP acid method was directly applicable to o-methoxy-substi-tuted alcohol 23 (entry 11), o-methyl-substituted alcohol 24 could not be enantioresolved as the CSDP acid esters, so the indirect method was adopted as follows o-hydroxymefhyl-substituted alcohol 25 was enantioresolved as CSDP esters, where the primary alcohol moiety was esterified (entry 12). Enantiopure alcohol (R)-(-i-)-25 was then converted to the target compound (P)-(-)-24. It should be noted that the absolute configuration of alcohol 24 was once estimated on the basis of an asymmetric reaction mechanism, but it was revised by this study. The data of alcohols 26 and 27 indicate that the HPLC separation as CSDP esters is easier for silyl ethers (entries 13 and 14). 

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. 

Fujita T, Obata K, Kuwahara S, Nakahashi A, Monde K, Decatur J, Harada N. (R)-(-l-)-[VCD(—)984]-4-Ethyl-4-meth-yloctane, a cryptochiral hydrocarbon with a quaternary chirality center. (1) Synthesis of enantiopure compound and unambiguous determination of absolute configuration. Eur. J. Org. Chem. 2010 6372-6384. 

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