Enantioselective and diastereodivergent construction of oxindole–pyrazolone conjugates bearing an alkenyl substituted quaternary chlorinated stereogenic centre†

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.