Synthesis of enantiopure aliphatic acetylene alcohols and determination of their absolute configurations by 1H NMR anisotropy and/or X-ray crystallography

The M alpha NP acid method has been applied to racemic aliphatic acetylene alcohols in order to simultaneously prepare enantiopure alcohols and to determine their absolute configurations by H-1 NMR anisotropy. Racemic acetylene alcohols 6 - 8, 11, and 20 were esterified with M alpha NP acid (S)-(+)-1 to yield diastereomeric MaNP esters which were efficiently separated by HPLC on silica gel with separation factors a in the range 1.60 - 1.93. The H-1 NMR anisotropy factors Delta delta [= delta(2nd fr.) - delta(1st fr.)] were calculated from the data of the first- (22a - 27a) and second-eluted M alpha NP esters (22b - 27b). The absolute configurations of the first-eluted esters were determined from the distribution of Delta delta values in the M alpha NP sector rule. In the case of M alpha NP ester 26b, the assigned absolute configuration was confirmed by X-ray crystallography. The solvolysis of M alpha NP esters yielded enantiopure acetylene alcohols 5 - 8 with established absolute configurations. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).