SYNTHESIS OF 2-SUBSTITUTED 4-METHYLENEGLUTAMIC ACIDS AND THEIR CYCLOPROPYL ANALOGS

The alkylation of the dianion 10 derived from ethyl 3-methylene-pyrogl utamate (9) allows the synthesis of 2-substituted 4-methylenepyrogluta mates 12, after final N-Boc protection. They can also be prepared by a lkylation at the 2-position of dianion 14 derived from ethyl pyrogluta mate, followed by methylenation at the 4-position and final N-Boc prot ection. Hydrolysis of methylene derivatives 12 let to the preparation of 2-substituted 4-methyleneglutamic acids 5. The cyclopropanation of 2-alkylated-4-methylenepyroglutamates 11 with diazomethane catalyzed b y Pd(OAc)(2) affords the cyclopropyl analogues 17 which, after the sam e treatment as described for compounds 11, are converted into the corr esponding 2-substituted 4,4-ethyleneglutamic acids 6.