Achiral Catalyst‐Induced Stereoselectivity Switch at Quaternary Stereocenter: Diastereodivergent Ring‐Opening Alkylation and Enantiodivergent Arylation of Oxindoles

Abstract The development of a unified strategy to achieve both diastereodivergence and enantiodivergence is a prominent yet challenging objective. In this study, a new strategy involving achiral Lewis acid ‐directed stereodivergence has been developed. An achiral metal salt is used as a control element to achieve a diastereoselectivity switch, which is unusual. By simply changing the achiral Lewis acids from a non‐lanthanide d ‐block metal salt (ZnCl 2 ) to a lanthanide f ‐block metal salt (DyCl 3 ), a diastereodivergent asymmetric ring‐opening alkylation of racemic oxindoles with oxabicyclic alkenes has been achieved, leading to a new series of chiral 3,3‐disubstituted oxindoles with three contiguous stereocenters bearing a dihydronaphthalen‐1‐ol motif with excellent enantioselectivities (up to > 99% ee) and diastereoselectivities (up to > 95:5 dr). Next, by simply switching the achiral metal Lewis acid cocatalysts while maintaining the same chiral catalyst, an enantiodivergent formal arylation has been achieved, providing chiral 3,3‐diaryl oxindoles featuring a triaryl‐substituted quaternary stereocenter. Diverse transformations of the chiral 3,3‐oxindoles delivered synthetically useful compounds. Those chiral 3,3‐disubstituted oxindoles have shown significant antiproliferative activity against HCT116 colorectal cancer cells. The relative and absolute configurations of these compounds exert prominent effects on the bioactivities, further highlighting the remarkable importance of catalytic asymmetric stereodivergent synthesis.