Absolute configuration, of alcohols

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

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). 

Fig. 9.22 The S absolute configuration of alcohol (+)-40 as determined by the H NMR anisotropy method using MaN P acid (a) DCC, DMAP, CSA/CH2CI2, r.t. [39].

Kobayashi Y, Hayashi N, Kishi Y. Application of chiral bidentate NMR solvents for assignment of the absolute configuration of alcohols scope and limitation. Tetrahedron Lett. 2003 44 7489-7491. 

Ghosh I, Zeng H, Kishi Y. Appfication of chiral lanthanide shift reagents for assigmnent of absolute configuration of alcohols. Org. Lett. 2004 6 4715-4718. 

Seco JM, Quinoa E, Riguera R. A Practical Guide for the Assignment of the Absolute Configuration of Alcohols, Amines and Carboxylic Acids by NMR. Tetrahedron Asymmetry... 

Conformational Analysis. Historically, the first model used to correlate the absolute configuration of alcohols with the NMR shifts and signs of the Ad values of the MPA esters was proposed by Mosher " and is, as in the case of MTPA derivatives, empirically generated from the study of several alcohols of known stereochemistry. For this reason, the validity of the method is related to the represen-tativity and scope of the series of alcohols initially studied. ... 

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