Asymmetric Synthesis of Pseudo C2-Symmetric 2-Methyl Substituted 1,3-Diols

Abstract

The diastereo- and enantioselective synthesis of pseudo C 2-symmetric, 2-methyl substituted, acetonide protected (4) and free 1,3-diols 5 employing the SAMP-hydrazone mothodology with virtually complete asymmetric induction (de ≥ 96%, ee ≥ 98-99%) is reported. The efficient protocol involves the asymmetric α,α"-bisalkylation of hydrazone 1, the epimerization-free Wittig olefination of the resulting ketones 2 and subsequent hydrogenation of the exo-methylene derivatives 3 with PtO2·H2O or Wilkinson's catalyst to afford the acetonide protected title compounds 4 in very good overall yields. Quantitative deprotection with trifluoroacetic acid to the free diols 5 is demonstrated.