Stereoselective syntheses of highly functionalized bicyclo[3.1.0]hexanes: a general methodology for the synthesis of potent and selective mGluR2/3 agonists.
[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.
Tan
Lushi
L
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. lushi_tan@merck.com
Yasuda
Nobuyoshi
N
Yoshikawa
Naoki
N
Hartner
Frederick W
FW
Eng
Kan Kaung
KK
Leonard
William R
WR
Tsay
Fuh-Rong
FR
Volante
Ralph P
RP
Tillyer
Richard D
RD
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006586:Hexanes / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D006586:Hexanes; D007202:Indicators and Reagents; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3