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 is reported for the construction of a rarely developed alkenyl substituted quaternary chlorinated stereogenic centre, featured in oxindole and pyrazolone pharmacophores. Remarkably, the configuration of the double bond was switchable via the combination of a suitable base and solvent. In addition, the enantioselective synthesis of Z-type products was achieved with natural quinidine as a catalyst, affording the chlorinated products in excellent yields and stereoselectivities. Preliminary ¹H-NMR titration was studied to gain insights into the control of the double bond's configuration. Moreover, the anti-tumour activity against the A549 cell-line of these newly synthesized chemical entities was evaluated, and the product (E)- was revealed to be a promising anti-tumour agent.