Stereoselective Syntheses of Highly Functionalized Bicyclo[3.1.0]hexanes:  A General Methodology for the Synthesis of Potent and Selective mGluR2/3 Agonists

• Published in: Journal of organic chemistry Vol. 70; no. 20; pp. 8027 - 8034
• Main Authors: Tan, Lushi, Yasuda, Nobuyoshi, Yoshikawa, Naoki, Hartner, Frederick W, Eng, Kan Kaung, Leonard, William R, Tsay, Fuh-Rong, Volante, Ralph P, Tillyer, Richard D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 30-09-2005
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Bridged Bicyclo Compounds - chemical synthesis; Bridged Bicyclo Compounds - chemistry; Chemistry; Chromatography, High Pressure Liquid; Exact sciences and technology; Hexanes - chemical synthesis; Hexanes - chemistry; Indicators and Reagents; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Organic chemistry; Preparations and properties; Receptors, Metabotropic Glutamate - agonists; Stereoisomerism; Cyclopropanation; Stereoselectivity; Agonist; Diol; Functionalization; Epoxide; Bicyclic compound; Selectivity; Chemical synthesis; mglu2 glutamate receptor; mglu3 glutamate receptor; Ring cleavage
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0511187

A Et3Al mediated intramolecular epoxide opening, cyclopropanation reaction is described. The transformation provided highly functionalized bicyclo[3.1.0]hexane systems in high efficiency and with perfect H or F endo selectivity. Application of this reaction to the synthesis of mGluR2/3 agonist 1 (43% overall yield) and a few intermediates suitable for the synthesis of other bicyclo[3.1.0]hexane mGluR2/3 agonists is discussed.