Diastereoselective synthesis of 4-alkylidene-2-amino-4-phosphonobutanoic acids

Olefination of α-silyl-, α-phosphoryl- and α-stannyl-stabilised phosphonate carbanions derived from cyclo-[l-AP4-d-Val] Li+4b–d− allow a (Z)-selective access to the α,β-substituted vinylphosphonates 7A–E that have been transformed into enantiomerically pure 4-alkylidene AP4 derivatives 12A,B and 13A,C. According to semi-empirical (PM3) calculations, the preference for like topologies in the intermediate adducts of the phosphonate addition step accounts for the highly (Z)-selective course of the ‘tin-Peterson-like’ olefination.