title: 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(1)
abstract: Enantiopure methyl D-alpha-trifluoromethyl-allo-threoninate 18 and L-alpha-trifluoromethylthreoninate 19 were synthesized using (R)-ethyl p-tolylsulfoxide 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 trifluoroacetic anhydride promoted "non-oxidative" Pummerer reaction (NOPR) of the diastereomeric intermediate beta-sulfinyl amines 14 and 15, obtained by condensation of (R)-ethyl p-tolylsulfoxide 13 with the N-Cbz imine of methyl trifluoropyruvate 12. The conclusive evidence for S(N)2-type stereoselectivity 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 transient intermediate, which was identified as the four membered cyclic sigma-sulfurane 27. This intermediate spontaneously rearranged (40 min, rt) into the corresponding sulfenamide 17, probably via an intramolecular displacement of the sulfinyl by a trifluoroacetoxy group, with inversion of configuration at the carbon stereocenter. The same process occurred for the diastereomeric beta-sulfinyl amine 14, but the sulfenamide 16 was formed at a very fast rate, thus precluding NMR detection of the corresponding sigma-sulfurane intermediate 26. One-pot treatment of the diastereomeric sulfenamides 16 and 17 with NaBH(4) afforded very good yields of the corresponding threoninates 18 and 19.
authors.affiliation: Dipartimento di Chimica del Politecnico di Milano, via Mancinelli 7, I-20131 Milano, Italy, and CNR - CSSON, via Mancinelli 7, I-20131 Milano, Italy.
authors.initials: M
authors.lastname: Crucianelli
authors.initials: P
authors.lastname: Bravo
authors.initials: A
authors.lastname: Arnone
authors.initials: E
authors.lastname: Corradi
authors.initials: SV
authors.lastname: Meille
authors.initials: M
authors.lastname: Zanda