Synthesis of enantioenriched aza-proline derivatives through gold(I)-catalyzed cyclization of chiral α-hydrazino esters

摘要

A selective gold(I)-catalyzed synthesis of chiral aza-proline derivatives has been developed by ring closure of enantioenriched α-hydrazino esters bearing an alkyne group. These are easily prepared through a synthetic strategy involving two key steps: organocatalyzed electrophilic amination of pent-4-ynal with dialkyl azodicarboxylate promoted by l-proline and functionalization of the triple bond by Sonogashira cross-coupling. This strategy allowed the preparation of a range of enantioenriched α-hydrazino esters that underwent ring closure by using Ph_3PAuCl/AgBF_4 as a catalytic system. Under these conditions, 5-exo-dig cyclization was favored over 6-endo-dig and aza-proline derivatives were obtained in good yields without epimerization at the stereogenic center. Influence of the catalytic system, hydrazine protecting group and alkyne substitution on the cyclization step has also been investigated.