Catalytic enantioselective synthesis of chiral 4-hydroxy 4′-substituted pyrazolones by the vinylogous aldol reaction of pyrazole-4,5-diones with 3-alkylidene-2-oxindoles

Here, a bifunctional quinine-derived benzamide catalyzed direct enantioselective vinylogous aldol reaction between 3-alkylidene-2-oxindoles and pyrazole-4,5-diones has been developed. This challenging protocol has been achieved via the H-bonding dual activation mode of the catalyst. Highly functional rich pyrazolone moieties having an oxindole core have been obtained with an excellent E/Z (>19 : 1), and high yields along with moderate enantioselectivity.

Automated summary

A novel catalytic system has been developed for the direct enantioselective vinylogous aldol reaction between 3-alkylidene-2-oxindoles and pyrazole-4,5-diones. The bifunctional quinine-derived benzamide catalyst achieved highly functional rich pyrazolone moieties with excellent E/Z selectivity (>19:1) and high yields, as well as moderate enantioselectivity through H-bonding dual activation mode.