Synthesis of fluorinated glutamic acid derivatives via vinylalumination

A variety of structural types of fluorinated allylic acetates, prepared by vinylalumination of fluorinated aldehydes, were reacted with the benzophenone imine of glycine tert-butyl ester to provide 4-(fluorobenzylidenyl)- and 4-(fluoroalkylidenyl) glutamic acid derivatives in 61-96% yield. The 4-(4-fluorobenzylidenyl) glutamic acid derivative was hydrolyzed to give the 4-(4-fluorobenzylidenyl)pyroglutamate and then hydrogenated to the 4-(4-fluorobenzyl)pyroglutamate. The catalytic enantioselective conjugate addition-elimination of the benzophenone imine of glycine tert-butyl ester with the fluorinated allylic acetates prepared from fluoral, pentafluorobenzaldehyde, and 2,6-difluorobenzaldehyde provided the corresponding 4-(fluoroalkylidenyl)- and 4-(fluorobenzylidenyl) glutamic acid derivatives in 42, 45 and 80% ee, respectively. (c) 2006 Elsevier B.V. All rights reserved.