Enantioselective syntheses of 2-amino-4-fluoropent-4-enoic acids. Isosteres of asparagine

Diastereoselective alkylation of (R)-(+)-camphor-based glycine or alanine e sterimines with 3-bromo-2-fluoropropene after hydrolytic deprotection gave (R)-(+)-2-amino-4-fluoropent-4-enoic acid with 38% overall yield and 90% ee , or (R)-(+)-2-amino-3-fluoro-2-methylpent-4-enoic acid (19% overall yield, 59% ee), respectively, Deprotection under drastic conditions was accompani ed by hydrolysis of the fluorovinyl moiety to give (R)-(-)-2-amino-4-oxopen tanoic acid hydrochloride with 28% overall yield and >95% ee. Ab initio cal culations of acetamide and 2-fluoropropene as models for a primary amide or a fluorovinyl group despite of their different electronic structure show a similar electrostatic potential on the van der Waals surface suggesting th eir isosteric behavior. (C) 1999 Elsevier Science Ltd. All rights reserved.