13 強力なアルコール光学分割能と磁気異方性効果をもつキラルカルボン酸の開発 : 光学分割と絶対配置決定への応用(口頭発表の部)

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Recently, we have found that 2-methoxy-2-(1-naphthyl)propionic acid (1, MαNP acid, Chart 1) was very useful for determination of absolute configurations of chiral alcohols including natural products. Racemic MαNP acid (1) was enantioresolved as its esters with various chiral alcohols. For example, a diastereomeric mixture of esters prepared from (±)-1 and (1R,3R,4S)-(-)-menthol (Scheme 2) was easily separated by HPLC on silica gel yielding esters (-)-7a and (-)-7b, the separation factor a being unusually large as 1.83 (Figure 1). The data of ^1H NMR chemical shift difference, Δδ=δ(R) ? δ(S), between diastereomers 7a and 7b, are much larger than those of conventional chiral auxiliaries, e.g., Mosher's MTPA and Trost's MPA acids (Figures 2-4). This acid 1 is therefore very powerful for determining the absolute configuration of chiral alcohols by the ^1H NMR anisotropy method (Figures 3 and 5). Solvolysis of the separated esters with NaOCH_3 in methanol and then with water, yielded enantiopure acid (S)-(+)-1, [α]D^<26> +67.4 (c 1.39, CHCl_3), and (R)-(-)-1. During those studies, we have also found that the acid 1 was very powerful for enantioresolution of various alcohols, especially aliphatic alcohols (Figure 6). The chiral acid 1 is a regular organic compound containing no hetero atoms, but its performance as a chiral auxiliary for enantioresolution of alcohols is great as shown below. The strong power of this acid 1 for diastereomers separation is demonstrated by the case of 2-butanol. Racemic 2-butanol was esterified with the chiral acid (S)-(+)-1; the obtained mixture of diastereomeric esters 8a and 8b was almost base-line separated by HPLC on silica gel (hexane/EtOAc 20: 1) as shown in Figure 6 (a): α=1.15. The acid 1 has thus a great ability to recognize the small difference between methyl and ethyl groups. As well known, chiral discrimination between methyl and ethyl groups is the most difficult in enantioresolution and also even in asymmetric reactions. Now we obtained a facile method to get enantiopure 2-butanol. We have applied this method to various 2-alkanols and 1-octyn-3-ol, which have been successfully resolved as shown in Figure 6. To determine the absolute configurations of the first-eluted diastereomeric esters by the ^1H NMR anisotropy method, the general scheme was proposed as shown in Figure 7. By applying the scheme, the absolute configurations of the first-eluted esters were determined as exemplified in Figure 8. To recover enantiopure alcohols, separated esters were reduced with LiAlH_4 or hydrolyzed with KOH/EtOH. When hydrolyzed with KOH/EtOH, the recovered acid 1 could be recycled for another resolution. The use of chiral MαNP acid 1 thus enables one to obtain enantiopure alcohols, and also to determine their absolute configurations simultaneously by the ^1H NMR anisotropy method.
天然有機化合物討論会の論文
2000-10-01

13 強力なアルコール光学分割能と磁気異方性効果をもつキラルカルボン酸の開発 : 光学分割と絶対配置決定への応用(口頭発表の部)

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