A Convenient Approach to the Enantiopure (1S,2S,4S,5S)-and (1R,2S,4R,5S)-2,5-Bis(phenylmethyl)-1,4-diazabicyclo[2.2.2]-octane

Cyclodipeptide (3 S,6S ) bis(phenylmethyl)piperazine 2,5 dione was prepared in high yield by heating phenylalanine methyl ester in toluene under reflux. The reduction of this cyclodipeptide with sodium NaBH 4 BF 3 in DME gave the (2 S,5S ) bis(phenylmethyl)piperazine, which, on heating with ethylene bromide and triethylamine, afforded the title compounds. This method was proved to be generally applicable to the synthesis of C 2 symmetric 2,5 disubstituted 1,4 diazabicyclo[2.2.2]octane from the corresponding natural or unnatural amino acid esters.