Enantiopure methyl D-R-trifluoromethyl-allo-threoninate 18 and L-R-trifluoromethylthreoninate 19 were synthesized using (R)-ethyl p-tolylsulfoxide as chiral R-hydroxyethyl anion equivalent. The key step was the SN2-type replacement of the sulfinyl auxiliary with a hydroxy group, via trifluoroacetic anhydride promoted “non-oxidative” Pummerer reaction (NOPR) of the diastereomeric intermediate â-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 SN2-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 ó-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 â-sulfinyl amine 14, but the sulfenamide 16 was formed at a very fast rate, thus precluding NMR detection of the corresponding ó-sulfurane intermediate 26. Onepot treatment of the diastereomeric sulfenamides 16 and 17 with NaBH4 afforded very good yields of the corresponding threoninates 18 and 19.

The “Non-Oxidative” Pummerer Reaction: Conclusive Evidence for SN2-Type Stereoselectivity, Mechanistic Insight, and Synthesis of Enantiopure L-r-Trifluoromethylthreoninate and D-r-Trifluoromethyl-allo-threoninate

CRUCIANELLI, MARCELLO;
2000

Abstract

Enantiopure methyl D-R-trifluoromethyl-allo-threoninate 18 and L-R-trifluoromethylthreoninate 19 were synthesized using (R)-ethyl p-tolylsulfoxide as chiral R-hydroxyethyl anion equivalent. The key step was the SN2-type replacement of the sulfinyl auxiliary with a hydroxy group, via trifluoroacetic anhydride promoted “non-oxidative” Pummerer reaction (NOPR) of the diastereomeric intermediate â-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 SN2-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 ó-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 â-sulfinyl amine 14, but the sulfenamide 16 was formed at a very fast rate, thus precluding NMR detection of the corresponding ó-sulfurane intermediate 26. Onepot treatment of the diastereomeric sulfenamides 16 and 17 with NaBH4 afforded very good yields of the corresponding threoninates 18 and 19.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11697/11602
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