Enantioselective preparation of ring-fused 1-fluorocyclopropane-1-carboxylate derivatives: en route to mGluR 2 receptor agonist MGS0028.
[reaction: see text] An approach to the densely functionalized fluorocyclopropane 14, a key framework toward the synthesis of mGluR 2 receptor agonist MGS0028 (1) is reported. The Trost AAA reaction enantioselectively introduced the key allylic stereogenic center and the alpha-fluoroester moiety. Stereoselective epoxidation followed by intramolecular epoxide ring opening efficiently constructed the 1-fluorocyclopropane-1-carboxylate matrix. This route can potentially be a general methodology for a concise, highly enantio- and stereoselective synthesis of 1-fluorocyclopropane-1-carboxylate derivatives.
Zhang
Fei
F
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. fei_zhang@merck.com
Song
Zhiguo J
ZJ
Tschaen
Dave
D
Volante
R P
RP
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000737:chemistry*; D003521:Cyclopropanes / Q000737:chemistry*; D003998:Dicarboxylic Acids / Q000138:chemical synthesis*; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism
C508463:1-fluorocyclopropane-1-carboxylate; D001643:Bridged Bicyclo Compounds; D002264:Carboxylic Acids; D003521:Cyclopropanes; D003998:Dicarboxylic Acids; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C418124:MGS 0028