Asymmetric Synthesis of 2‐Trifluoromethyl‐1,2,3‐triols

Abstract

AbstractThe asymmetric synthesis of the 2‐trifluoromethylated 1,2,3‐triols 5 starting from 2,2‐dimethyl‐1,3‐dioxan‐5‐one (1) is described. The enantiomerically pure α‐alkylated dioxanones 3 and 6 were obtained via the SAMP/RAMP hydrazone methodology. Trifluoromethylation of the monoalkylated dioxanones 3 with (trifluoromethyl)trimethylsilane in the presence of TBAF gave the 2‐trifluoromethylated acetonide‐protected triols 4 in high diastereo‐and enantiomeric excesses (de ≥ 96 %, ee = 92 – ≥ 98 %) and good overall yields (52–97 %). Finally, deprotection of the triol under acidic conditions afforded the title compound 5 (de ≥ 96 %, ee = 95, 96 %) as a typical example. In addition, the methodology was extended to the trialkylated dioxanone 6 leading to the trifluoromethylated alcohol 7 with two neighbouring quaternarystereocenters in good yield (77 %) and very good diastereo‐ and enantiomeric excesses (de ≥ 96 %, ee = 98 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)