Enantioselective Michael-Proton Transfer-Lactamization for Pyroglutamic Acid Derivatives: Synthesis of Dimethyl-(S,E)-5-oxo-3-styryl-1-tosylpyrrolidine-2,2-dicarboxylate.

Abstract

A. Dimethyl 2-amino((4-methylphenyl)sulfonamido)malonate (2). To a single-necked, 500 mL round-bottomed flask containing a football-shaped, teflon-coated stir bar (5 cm) and fitted with a 24/40 glass, threaded gas-inlet adapter with a silicone/PTFE septa (Figure 1A) (Note 2), in-turn connected via chemically resistant tubing to a vacuum/nitrogen manifold is added commercially available dimethyl aminomalonate hydrochloride (1, 12.5 g, MeO2C CO2Me NH2 •HCl Ts2O, NEt3 THF, 0 to 23 °C MeO2C CO2Me NHTs