Synthesis of Enantiopure Aliphatic Acetylene Alcohols and Determination of Their Absolute Configurations by ¹H NMR Anisotropy and/or X‐ray Crystallography

Abstract

The MαNP acid method has been applied to racemic aliphatic acetylene alcohols in order to simultaneously prepare enantiopure alcohols and to determine their absolute configurations by 1 H NMR anisotropy. Racemic acetylene alcohols 6-8, 11, and 20 were esterified with MαNP acid (S)-(+)-1 to yield diastereomeric MαNP esters which were efficiently separated by HPLC on silica gel with separation factors α in the range 1.60-1.93. The 1 H NMR anisotropy factors ∆δ [= δ(2nd fr.) -δ(1st fr.)] were calculated from the data of the first-(22a-

A general method for the synthesis of enantiopure aliphatic chain alcohols with established absolute configurations. Part 2, via catalytic reduction of acetylene alcohol MαNP esters

“…12-14, 16 We have not encountered any exceptions where 1 H NMR anisotropy using MaNP esters conflicted with the X-ray crystallography. This fact has established the empirical 1 H NMR anisotropy method as a more reliable one.…”

“…Racemic aliphatic alcohols with long chains 5 and 7 were easily synthesized by catalytic hydrogenation of the corresponding acetylene alcohols 8 and 9 16 with H 2 and PtO 2 in diethyl ether (Scheme 1). It is noteworthy that both alcohols were obtained in quantitative yield despite having aliphatic long chains, although (±)-19-octatriacontanol 7 was barely soluble even in CHCl 3 .…”

“…16 Since these acetylene alcohol MaNP esters were chemically correlated to MaNP esters 16-18 as will be discussed below, their absolute configurations were established.…”

“…Hence, we adopted the indirect method as follows; we have reported that diastereomeric MaNP esters of acetylene alcohols with aliphatic chains can be readily separated by HPLC on silica gel, 16,17 and some data are listed in Table 2. For example, 10-octadecyn-9-ol MaNP esters 21a/21b were separable with a = 1.61, and hence preparative scale separation was possible.…”

Determination of optical purity and absolute configuration of natural 12‐hydroxystearic acid by the 1H NMR anisotropy method

“…These methods can be generalized to a variety of secondary alcohols to synthesize enantiopure alcohols. Secondary alcohols which have acetylene bond are easy to assign the 1 H NMR peaks of products following the Sector rule [16]. This chiral MaNP acid 1 facilitates preparation of enantiomers with 100% ee and also absolution configurational assignment via the 1 H NMR anisotropy.…”