Diastereomerically and Enantiomerically Pure 2,3-Disubstituted Pyrrolidines from 2,3-Aziridin-1-ols Using a Sulfoxonium Ylide:  A One-Carbon Homologative Relay Ring Expansion

Abstract

An ylide-based aza-Payne rearrangement of 2,3-aziridin-1-ols leads to an efficient process for the preparation of pyrrolidines. The aza-Payne rearrangement under basic reaction conditions favors the formation of epoxy amines. Subsequent nucleophilic attack of the epoxide by the ylide yields a bis-anion, which upon a 5-exo-tet ring-closure yields the desired pyrrolidine, thus completing the relay of the three-membered to the five-membered nitrogen-containing ring system. This process takes place with complete transfer of stereochemical fidelity and can be applied to sterically hindered aziridinols.

Ring Expansions of Activated Aziridines and Azetidines

“…Borhan and co-workers extensively studied the aza-Payne/hydroaminationmodified hydroamination reaction of aziridinols for the synthesis of highly substituted fused pyrrolidines [79][80][81][82]. They reported dimethylsulfoxonium ylidebased aza-Payne rearrangement of 2,3-disubstituted aziridinols for the synthesis of highly functionalized pyrrolidine derivatives [79]. Later the group devised an aza-Payne/hydroamination reaction for the synthesis of pyrrolidine ring system in the form of a strained enamide 128 [80].…”

New Methodology for the Conversion of Epoxides to Alkenes

“…The residue was taken up in CH 2 Cl 2 (3 ϫ 40 mL), washed with saturated aqueous NH 4 Cl solution (3 ϫ 40 mL), water (40 mL) and brine (40 mL), and then dried (MgSO 4 ). Evaporation of the solvent gave a residue which was purified by silica flash column chromatography (petroleum ether/ EtOAc = 9:1) to generate the dibenzyl ether 19 [27] …”

“…The mixture was diluted with CH 2 Cl 2 (70 mL), washed with 1  NaOH (3 ϫ 70 mL), water (70 mL) and dried (MgSO 4 ). Evaporation of the solvent gave a residue which was purified by silica flash column chromatography (petroleum ether/EtOAc = 17:3) to afford the epoxide 24 [27] ( washed with 1  NaOH (3 ϫ 50 mL) and water (50 mL), and then dried (Na 2 SO 4 ). Evaporation of the solvent gave a residue which was purified by silica flash column chromatography (petroleum ether/EtOAc = 17:3) to afford the epoxide 25 [32] (388 mg, 96 %) as a colorless oil.…”

“…The reaction mixture was stirred and warm to room temperature for 1.5 d. The mixture was extracted with CH 2 Cl 2 (3 ϫ 50 mL), washed with water (50 mL) and dried (MgSO 4 ). Evaporation of the solvent gave a crude mixture which was purified by silica flash column chromatography (petroleum ether/EtOAc = 4:1) to give the epoxy alcohol 28 [27] (243 mg, 25 %). R f = 0.11 (petroleum ether/EtOAc = 7:3).…”

Pyrrolidines: Priveleged Structure in Bioactive Molecules and Synthesis

“…proline), 20 and (b) construction of the pyrrolidine ring from different acyclic precursors. Intramolecular hydroamination, 21 cycloisomerization of dienes, 22 intramolecular aza-michael reaction, 23 aza-payne rearrangement, 24 double-michael reaction, 25 reductive cyclization of acetylenic aldehydes, 26 [3+2]-annulation, 27 alkenylative cyclization, 28 annulation reaction of 1,1-cyclopropanediesters, 29 Nheterocyclization of primary amines, 30 iodo-aldol cyclization, 31 reduction of substituted pyrroles, 32 ionic iodine atom transfer cyclization 33 and cyclization of γ-(N-substituted) alkenes with aryl bromide 34 are reported in the second category.Another traditional method to effect the pyrrolidine ring formation involves intramolecular cyclization of a nitrogen nucleophile onto a pendant olefin using activating reagents such as I 2 or Hg(OAc) 2 . .…”