Asymmetric Michael Addition of 3-Chlorooxindoles with Vinylidene Bisphosphonates: Synthesis of 3,3-Disubstituted 3-Chlorooxindoles and Spirocyclopropane-Fused Oxindoles

The 3,3-disubstituted oxindole scaffold is a privileged structure in medicinal chemistry. Herein, we report a highly enantioselective Michael addition of 3-chlorooxindoles to vinylidene bisphosphonates catalyzed by a bifunctional cinchona alkaloid-derived organocatalyst. This strategy provides efficient access to enantiomerically pure 3,3-disubstituted oxindoles bearing a germinal bisphosphonate group in excellent yields and enantioselectivities (up to 98% yield, 99% ee). Furthermore, the Michael adducts can be readily transformed into novel bisphosphonate-functionalized spirocyclopropane-oxindoles via stereospecific annulation. This work provides a direct route to unprecedented, enantiomerically pure oxindole-bisphosphonate hybrids with potential biological relevance.