Stereoselective syntheses of highly functionalized bicyclo[3.1.0]hexanes: a general methodology for the synthesis of potent and selective mGluR2/3 agonists

Lushi Tan; Nobuyoshi Yasuda; Naoki Yoshikawa; Frederick W Hartner; Kan Kaung Eng; William R Leonard; Fuh-Rong Tsay; Ralph P Volante; Richard D Tillyer

doi:10.1021/jo0511187

Stereoselective syntheses of highly functionalized bicyclo[3.1.0]hexanes: a general methodology for the synthesis of potent and selective mGluR2/3 agonists

J Org Chem. 2005 Sep 30;70(20):8027-34. doi: 10.1021/jo0511187.

Authors

Lushi Tan¹, Nobuyoshi Yasuda, Naoki Yoshikawa, Frederick W Hartner, Kan Kaung Eng, William R Leonard, Fuh-Rong Tsay, Ralph P Volante, Richard D Tillyer

Affiliation

¹ Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. [email protected]

PMID: 16277324
DOI: 10.1021/jo0511187

Abstract

[Chemical reaction: See text] 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.

MeSH terms

Bridged Bicyclo Compounds / chemical synthesis*
Bridged Bicyclo Compounds / chemistry
Chromatography, High Pressure Liquid
Hexanes / chemical synthesis*
Hexanes / chemistry
Indicators and Reagents
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
Receptors, Metabotropic Glutamate / agonists*
Stereoisomerism

Substances

Bridged Bicyclo Compounds
Hexanes
Indicators and Reagents
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor 2
metabotropic glutamate receptor 3