ABSOLUTE CONFIGURATIONS BY X-RAY AND H NMR 697 In the case of halogenated alcohols 29 and 30.their heenamntiopee )30 ws trea A=5=55作 Fg12.ORTEP draing of图-(-26a“ (entry 6).Ther )rem 26 inTHF yielded h own in.Table 2.the tooled to various supsn tiopure alce g35.37-4号 rations. the indirect chemical co ,and51-56 acid alco e 36 ar way bs ard mar dternined 10 & adopted as In the case of alcohols 27 and 28.those solved as CSDP esters, wher the primary alcoho erified (entry re a chir by 6 was 12)he s 1 and 8. and the a but it The lata o be oted that the on as e gel than the co nding CSP acid esters:s aration fac toohcrrehimgog Alcohol (3R,4R)-(+)-47 is a r the syn es in one rotationa Chirality DOI 10.1002/chinin Figure 12, from which the absolute configuration of the alcohol part was clearly determined as R based on the absolute configuration of the camphorsultam moiety used as an internal reference. The R absolute configuration of 26a was also confirmed by the heavy atom effect of two chlorine and sulfur atoms contained. The reduction of the first-eluted ester (R)-(2)-26a with LiAlH4 in THF yielded enantiopure alcohol (R)-(1)-25. 66 Although the reduction with LiAlH4 was used here to recover the alcohol, we found later that the solvolysis with K2CO3 in MeOH as a more mild condition is also applicable to most CSDP esters. As shown in Table 2, the method using CSDP and/or CSP acids has been successfully applied to various substi￾tuted diphenylmethanols 27–33, 35, 37–42, and 51–56 (entries 2–14 and 23–28). Namely the diastereomeric esters prepared from racemic alcohols and CSDP acid (1S,2R,4R)-(2)-1 were effectively separated by HPLC on silica gel with separation factor a 5 1.10–1.34. It is known that if the separation factor a is larger than 1.10, the two components are baseline separable, yielding pure com￾pounds. In the case of alcohols 32, 38, 40, 51, 52, and 54–56, the CSDP acid method has been applied in a straightforward manner; the separated CSDP esters were recrystallized giving single crystals, which were subjected to X-ray crystallography (entries 7, 11, 12, 23, 24, and 26– 28). The absolute configurations of the alcohol parts were thus explicitly determined. In the case of alcohols 27 and 28, those compounds were previously enantioresolved by means of CSP acid (1S,2R,4R)-(2)-2, a similar chiral auxiliary developed by us as shown in Figures 1 and 8, and the absolute configu￾rations of their CSP esters were determined by X-ray crys￾tallography (entries 20 and 30 ). So, by comparison with the data, the absolute configurations of CSDP acid esters of alcohols 27 and 28 were established by chemical correla￾tion. It should be noted that the CSDP acid esters of 27 and 28 were more effectively separated by HPLC on silica gel than the corresponding CSP acid esters: separation fac￾tor a 5 1.20–1.26 vs. 1.1 (entries 2, 20 , 3, and 30 ). In gen￾eral, CSP acid esters have low solubility, possibly due to too better crystallinity, resulting in longer elution time and smaller a value in HPLC on silica gel. In addition, CSP esters were often obtained as fine needles, which were unsuitable for X-ray crystallography. Therefore CSDP acid 1 is more useful in most cases than CSP acid 2. In the case of halogenated alcohols 29 and 30, their diastereomeric CSDP esters were obtained as fine crys￾tals, which were unsuitable for X-ray crystallography. So, as described above, the enantiopure alcohol (2)-29 recov￾ered was converted to camphanate ester, the absolute con- figuration of which was determined by X-ray crystallogra￾phy as R (entry 4, Table 2). Alcohol (2)-30 was treated in the same way, but its camphanate ester was not suitable for X-ray analysis (entry 5). The absolute configuration of (2)-30 was determined as R by the comparison of its CD spectrum with that of (R)-(2)-29. Methyl-substituted alcohol 31 could not be enantiore￾solved by the CSDP acid method, because of the small dif￾ference in substituent effects: Me vs. H (entry 6). There￾fore, we have adopted the chemical conversion method as follows: racemic alcohol 32 with 4-Me and 40 -Br groups was effectively enantioresolved as CSDP esters, the abso￾lute configuration of which was determined by X-ray crys￾tallography (entry 7). The enantiopure alcohol (R)-(2)-32 obtained was reduced to remove Br atom yielding (S)-(2)- 31. Alcohols 34 and 36 are very unique chiral compounds, the chirality of which is generated by the substitution of isotopes: in the case of 34, H vs. D; in the case of 36, 12C vs. 13C. So, it is very difficult to recognize directly such an ultimately small chirality. To synthesize enantiopure alco￾hols 34 and 36, and to determine their absolute configu￾rations, the indirect chemical conversion method was employed as follows. For example, deuterium-substituted/ 4-Br alcohol 35 was similarly enantioresolved as in the case of compound 29 (entry 9). The enantiopure alcohol (S)-(2)-35 obtained was reduced to remove the Br atom yielding [CD(2)270.4]-(S)-34, which exhibits a negative CD Cotton effect at 270.4 nm. In a similar way, 13C-substi￾tuted diphenylmethanol [CD(2)270]-36 was synthesized in an enantiopure form and its absolute configuration was determined as S (entry 10). Although the CSDP acid method was easily applicable to o-methoxy-substituted alcohol 38 (entry 11), o-methyl￾substituted alcohol 39 could not be enantioresolved as the CSDP acid esters. So, the indirect method was adopted as follows: o-hydroxymethyl-substituted alcohol 40 was enan￾tioresolved as CSDP esters, where the primary alcohol moiety was esterified (entry 12). Enantiopure alcohol (R)- (1)-40 was then converted to the target compound (R)- (2)-39. It should be noted that the absolute configuration of alcohol 39 was once estimated on the basis of asymmet￾ric reaction mechanism, but it was revised later by this study. The data of alcohols 41 and 42 indicate that the HPLC separation as CSDP esters is easier for silyl ethers (entries 13 and 14). The CSDP acid method was applicable to benzyl alco￾hols 43–46 and naphthalene alcohols 47–49, the CSDP esters of which were effectively separated by HPLC on silica gel with a 5 1.11–1.38 (entries 15–21). In addition, except the case of 45, the absolute configurations of their CSDP esters were determined by X-ray crystallography. Alcohol (3R,4R)-(1)-47 is a key compound for the syn￾thesis of a light-powered chiral molecular motor [CD(2)237.2]-(2)-59a, which rotates in one rotational Fig. 12. ORTEP drawing of CSDP ester (R)-(2)-26a. 66 ABSOLUTE CONFIGURATIONS BY X-RAY AND 697 1 H NMR Chirality DOI 10.1002/chir