Compounds possessing propargylic (prop-2-ynylic) system are very important building blocks for organic chemistry. Among them, preparation of enantiomeric homopropargyl alcohols (but-3-yn-1-ols) constitutes a key-challenge for asymmetric synthesis and thus drawn tremendous attention from the synthetic community in the last few decades. In this work, the catalytic performance of a set of commercial lipases has been investigated for enantioselective transesterification of 1-phenylhomopropargylic alcohols under kinetically-controlled conditions. Lipase from Burckholderia cepacia (BCL) immobilized either on ceramic (Amano PS-C II) or diatomaceous earth (Amano PS-IM) turned out to be the most active and enantioselective enzyme preparations (E ≫ 500) furnishing both resolution products of the racemic 1-phenylbut-3-yn-1-ol in highly enantiomerically enriched form (up > 99% ee). Variable reaction parameters, such as the acyl-group donor reagent as well as solvent, were additionally screened to establish their impact on the stereochemical outcome. For optimal biocatalytic systems established with model substrate, the enzymatic transformations were extended toward preparative-scale KR of 8 other differently para-phenyl-substituted homopropargylic sec-alcohols, which resulted in the synthesis of (S)-alcohols (96-100% ee) and the respective (R)-acetates (92-100% ee) in 19-44% yield, accordingly. Additionally, the crystal structure of (1R)-1-(4-nitrophenyl)but-3-yn-1-yl acetate has been evaluated for the first time and helped to assess stereopreference of the studied BCL.
Keywords: Barbier reaction; Biocatalysis; Chiral alcohols; Homopropargyl alcohols; Kinetic resolution; Lipases.
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