Asymmetric Catalytic (3 + 2) Cyclization and Sequential Reaction to Construct Dihydrofuran- and Azepine-Based Spirooxindoles

The enantioselective formal (3 + 2) cyclization and sequential reaction of 2-malononitrile-substituted oxindoles with benzaldehydes and <i>ortho</i>-aminobenzaldehydes were achieved by chiral <i>N,N</i>'-dioxide/metal complex Lewis acid catalysts. This protocol supplies facile and efficient access to highly functionalized chiral dihydrofuran- and azepine-based spirooxindoles. Based on the control experiments and the deuterium labeling studies, the interconversion of (3 + 2) diastereomeric intermediates under the reaction conditions and reversible 1,5-H transfer step were disclosed.