The "non-oxidative" Pummerer reaction: Conclusive evidence for S(N)2-type stereoselectivity, mechanistic insight, and synthesis of enantiopure L-alpha-trifluoromethylthreoninate and D-alpha-trifluoromethyl-allo-threoninate

Enantiopure methyl D-alpha-trifluoromethyl-allo-threoninate 18 and L-alpha- trifluoromethylthreoninate 19 were synthesized using (R)-ethyl p-tolylsulfo xide as chiral alpha-hydroxyethyl anion equivalent. The key step was the S( N)2-type replacement of the sulfinyl auxiliary with a hydroxy group, via tr ifluoroacetic anhydride promoted "non-oxidative" Pummerer reaction (NOPR) o f the diastereomeric intermediate beta-sulfinyl amines 14 and 15, obtained by condensation of (R)-ethyl p-tolylsulfoxide 13 with the N-Cbz imine of me thyl trifluoropyruvate 12. The conclusive evidence for S(N)2-type stereosel ectivity of the NOPR was achieved by X-ray diffraction of both the starting diastereomer 14 and the p-bromobenzoate 25, obtained from the threoninate 19. NMR monitoring of the NOPR performed on 15 allowed the detection of a t ransient intermediate, which was identified as the four membered cyclic sig ma-sulfurane 27. This intermediate spontaneously rearranged (40 min, rt) in to the corresponding sulfenamide 17, probably via an intramolecular displac ement of the sulfinyl by a trifluoroacetoxy group, with inversion of config uration at the carbon stereocenter. The same process occurred for the diast ereomeric beta-sulfinyl amine 14, but the sulfenamide 16 was formed at a ve ry fast rate, thus precluding NMR detection of the corresponding sigma-sulf urane intermediate 26. One-pot treatment of the diastereomeric sulfenamides 16 and 17 with NaBH4 afforded very good yields of the corresponding threon inates 18 and 19.