Ergiebige Herstellung von (R)‐ und (S)‐3,3,3–Trifluormilchsäure und von (R)‐ und (S)‐(Trifluormethyl)oxiran

Abstract

Simple Access to (R)‐ and (S)‐3,3,3–Trifluorolactic Acid and to (R)‐ and (S)‐(Trifluoromethyl)oxiraneEthyl trifluoropyruvate (from hexafluoropropylene oxide) is reduced by NaBH4 to rac‐trifluorolactic acid which is resolved on a 100–g scale by salt formation with (R,R)‐ and (S,S)‐2–amino–1‐phenyl–1,3–propanediol (readily available intermediates of industrial chloroamphenicol synthesis). The enantiomerically pure trifluorolactic acids (>99% ee by GC analysis on cyclodextrin columns) are converted into (R)‐ and (S)‐(trifluoromethyl)oxirane in an overall yield of 73% by the following steps: esterification, THP protection of the OH group, LAH reduction and mesylation to the 2–THP–protected mesylate of 3,3,3–trifluoro–1,2–propanediol, and one–pot deprotection (Dowex 50) and cyclization (NaOCH2CH2OH) in ethylene glycol. The enantiomeric purity of the oxirane (b.p. 39C, isolated on a 10–g scale) was determined by GC to be >99%. Possible synthetic targets are mentioned which should be accessible in enantiomerically pure form from the (trifluoromethyl)oxirane described here.