EFFICIENT SYNTHESIS OF 4-METHYLENE-L-GLUTAMIC ACID AND ITS CYCLOPROPYL ANALOG

4-Methylene-L-glutamic acid (1) and its cyclopropyl analogue 2 were obtained from ethyl N-Boc-pyroglutamate (3) in 2 and 3 steps, respectively. The key intermediate, ethyl N-Boc-4-methylenepyroglutamate (4) was prepared by reaction of the lithium lactam enolate with Eschenmoser's salt. Cyclopropyl derivative 2 was also prepared from (S)-2-(terf-butyl)-3-methyl-4-imidazolidinone (7) in 3 steps. The intermediate 9 was obtained by diastereoselective reaction of the lithium enolate of 7 with butyl (2-tosylmethyl)acrylate (8).