We present the first stereoselective synthesis of phosphonic and phosphinic analogues
not only of (2S,3aS,6aS)-octahydrocyclopenta[b]pyrrole-2-carboxylic acid, the pivotal intermediate in ramipril synthesis, but also
of all its cis-fused stereoisomers. Key to this accomplishment is the highly diastereoselective
synthesis of cis-fused bicyclic (3aS,6aS)- and (3aR,6aR)-hexahydrocyclopenta[b]pyrrol-2-one using Meyers’ tricyclic lactam methodology. The nucleophilic addition
of trimethyl phosphite or dimethyl phenylphosphonite to chiral N-acyliminium ions affords the diastereoisomers, which are easily separated by column
chromatography. The diastereoselectivity in the nucleophilic addition of the phosphorus
reagents is completely consistent with our previous reports and all synthesized compounds
were fully characterized.
Key words
stereoselective synthesis - α-aminophosphonic acids - α-aminophosphinic acids - nitrogen
heterocycles -
N-acyliminium ions - amino acids
