Organocatalytic Remote Asymmetric Inverse-Electron-Demand Oxa-Diels-Alder Reaction of Allyl Ketones with Isatin-Derived Unsaturated Keto Esters

A remote cascade asymmetric inverse-electron-demand oxa-Diels-Alder reaction of allyl ketones with isatin-derived beta,gamma-unsaturated alpha-keto esters has been developed in the presence of a chiral bifunctional squaramide catalyst. Taking advantage of the secondary amide activating group, a series of enantioenriched 3,4'-pyranyl spirooxindole derivatives bearing three contiguous chiral centers were attained in high yields (84 to >99%) with excellent enantioselectivities (96-99% ee). Moreover, the gram-scale synthesis and the construction of 1-benzazepine scaffold by the product were also demonstrated.