Organocatalyzed route to enantioenriched pipecolic esters: decarboxylation of an aminomalonate hemiester

Enantioenriched pipecolic esters were prepared in good yields in the decarboxylation, at room temperature, of N-protected piperidinohemimalonates catalyzed by cinchona alkaloids. Enantiomeric excesses as high as 72% were obtained when using 9-epi-cinchonine and the N-benzoyl substituted piperidinohemimalonate. A detailed study of the different reaction parameters revealed that the selectivity of this noncovalent organocatalyzed reaction is strongly dependent on the solvent, toluene or carbon tetrachloride being the best ones. The whole process based on the malonic acid synthesis was successfully tested on a 10 mmolar scale and established a practical alternative to the asymmetric protonation of lithium enolates.