Zirconium-Mediated Intramolecular Ester Transfer Reaction:  Synthesis of α-Substituted γ-Aminobutyric Acid (GABA) Derivatives

Abstract

[reaction: see text]. The zirconium-mediated intramolecular ester transfer reaction of N-alkenyl carbamate derivatives proceeded to give alpha-substituted gamma-aminobutyric acid (GABA) derivatives in good to excellent yields. Quenching experiments of the reaction mixture with iodine or O2 indicated the presence of a cyclopropane intermediate. The resulting iodide was converted to 2-substituted pyrrolidine-3-carboxylate and/or alpha-alkylidene-gamma-aminobutyric acid derivatives in a stereospecific manner.

An Improved Ring‐Closing Metathesis Approach to Fluorinated and Trifluoromethylated Nitrogen Heterocycles

“…The ether layers were dried (MgSO 4 ), evaporated and the residue was purified using column chromatography (heptane/EtOAc, 10:1 to 6:1) to give 11 (152 mg, 54 %) as a colorless oil. [19] To a solution of compound 9 (100 mg, 0.38 mmol) in toluene (5 mL) were added PPh 3 (202 mg, 0.77 mmol), 3-buten-2-ol (40 µL, 0.46 mmol) and diethyl azodicarboxylate (80 µL, 0.61 mmol). The mixture was heated at 50°C for 12 h, then the solvent was evaporated and the residue was purified using column chromatography (heptane/EtOAc, 20:1) to give 12 ( …”

Diastereoselective Intramolecular Ester Transfer Reaction ofN-Alkenylcar­bamate Derivatives Mediated by Zirconocene-Butene Complex: Preparation of α,γ-Disubstituted γ-Aminobutyric Acid (GABA) Derivatives and 2,4-Di­substituted Pyrrolidine Derivatives

“…1 We have recently demonstrated successful examples of zirconium mediated intramolecular alkene-carbonyl coupling reaction of tert-butyl N-alkenyl-N-sulfonylcarbamate derivatives to give ester group transferred product (Scheme 1). 11,12 We have also clarified the reaction pathway on the basis of the observed stereospecificities in the iodination reactions of the reaction intermediates formed from both E-and Z-isomer of 3-akenylcarbamate derivatives. 11 As shown in Scheme 1 the reaction pathway can be simply illustrated using 3-butenylcarbamate derivative 1a.…”

“…11,12 We have also clarified the reaction pathway on the basis of the observed stereospecificities in the iodination reactions of the reaction intermediates formed from both E-and Z-isomer of 3-akenylcarbamate derivatives. 11 As shown in Scheme 1 the reaction pathway can be simply illustrated using 3-butenylcarbamate derivative 1a. The ligand exchange reaction of zirconocene equivalent 'Cp 2 Zr' with carbon-carbon double bond in the substrate 1a gave zirconacyclopropane intermediate A and then it coupled with carbonyl moiety intramolecularly to form a bicyclo [3.3.0] ate C through the facile cleavage of bridgehead carbonnitrogen bond by attacking the nucleophilic carbon center bearing zirconium atom.…”

Synthesis of γ‐Aminobutyric Acid Analogs

“…(AE)-a-Substituted GABA analogs have been prepared by a range of synthetic methodologies, including the palladium-catalyzed rearrangement of a-cyanocyclopropanone hydrates, which occurs with internal proton transfer, providing access to selectively deuterated a-amino acids [35] and zirconium-mediated intramolecular ester transfer reaction of N-alkenyl-N-tosyl carbamates derivatives [36].…”

“…The reactions, catalyzed by either proline containing peptides [38], or (S)-diphenylprolinol silyl ether (34) (Scheme 14.8) [39], afford (36) in high yield (95%) and enantioselectivity (>95% e.e. ), after reduction with NaBH 4 .…”