Enantioselective and Diastereodivergent Construction of Oxindole-pyrazolone Conjugates Bearing an Alkenyl Substituted Quaternary Chlorinated Stereogenic Centre

Abstract

Chlorinated stereogenic carbon centres are important elements both in pharmaceutical reagents and synthetic intermediates. Herein, a novel methodology was reported for the construction of rarely developed alkenyl substituted quaternary chlorinated stereogenic centre, featuring oxindole and pyrazolone pharmacophores. Remarkably, the configuration of the double bond was switchable via the combination of suitable base and solvent. In addition, the enantioselective synthesis of the Z-type products was achieved with natural quinidine as catalyst, affording the chlorinated products in excellent yields and stereoselectivities. Preliminary ¹H-NMR titration was studied to give insights into the control of the double bond’s configuration. Moreover, the anti-tumour activity against A549 cell-line of these newly synthesized chemical entities was evaluated, and the product (E)-5ca was revealed as promising anti-tumour reagent.