Enantioselective Access To Spirooxindoles Via A Domino Michael Addition/Cyclization Reaction Of 3-Acylaminooxindoles

Nitrogen heterocyclic framework is a kind of very important and structura lly ubiquitous motifs in many natural compounds, especially the spirooxindole moiety as a core framework structure usual y has the characteristics of biological activity and potential medicinal value. Owing to these peculiarities, a large amount of attentions of many organic workers have been attracted and enormous energy to synthesis this skeleton has been invested. In the past few years, although, practical and efficie nt strategies to assemble polyfunctional spirooxindole framework and spirooxindo le-based molecules with more than one chiral center have been reported, to develop more creative synthetic approachs for assembling architecturally complex spirooxindo le molecules are still necessary.In this paper, we have developed a novel use of the chiral organocatalyt ic enantioselective domino Michael addition/cyclization of 3-acylaminooxindoles as new bis-nucleoplilic reagents andα,β-unsaturated pyrazolecarboxamides as bis-electrophiles for construction of spirooxindole terahydroquindolines. Through the screening of catalyst, solvent, temperature, and additives, the optimum conditions were determined. Subsequently, with the optimized reaction conditions, we surveyed the ubiquity of the reaction substrates. Notably, the corresponding cascade process addults were obtained in high mixture of diastereomers’ yields(up to 99%) and excel ent enantioselectivities(up to 98% ee) under mild reaction conditions. The structural elucidation upon NMR and HRMS analysis. The absolute configuration of the cyclization product were determined by single crystal X-ray diffraction analysis.