Dinuclear Zinc Or Primary-amine-catalyzed Desymmetric Intramolecular Aldolization: An Enantioselective Construction Of Spiro[cyclohexanone-oxindole] Derivatives

1. Dinuclear zinc catalyzed desymmetric asymmetric intramolecular aldol reaction for synthesis of spiro[cyclohexanone-oxindole] derivatives and spiro[cyclohexenone-oxindole] derivativesSpiro oxindole backones exist in many important pharmaceutical intermediates and natural products, such as some inflammatory inhibitors. In our further research on the synthesis of chiral spiro oxindole compounds, the asymmetric desymmetric intramolecular aldolization of indole derivatives has been efficiently catalyzed by Trost’s bis-Pro Phenol dinuclear zinc complexes to attain chiral spiro[cyclohexanone-oxindole] and spiro[cyclohexenone-oxindole] derivatives derivatives in good yields, good diastereoselectivity(>20:1 dr) and high enantioselectivity(up to 99% ee). It is a new process for the synthesis of these types of spiro-oxindole compounds.2. Cinchona alkaloids derived primary amine catalyzed desymmetric intramolecular aldolization for synthesis of spiro[cyclohexenone-oxindole] derivativesAsymmetric organic small molecule catalysis has become a powerful tool for the synthesis of optically active compounds. We found that the combination of a cinchona-based chiral primary amine and a benzoic acid is an efficient catalyst system for the asymmetric desymmetric intramolecular aldolization of indole derived diketone compounds, providing chiral spiro[cyclohexenone-oxindole] derivatives in high yield(up to 98%) with excellent enantioselectivities(up to 95% ee). The present protocol is endowed some features of include excellent stereoselective control, operational simplicity, benign functional compatibility as well as good and highly efficient one-pot synthesis of the sophisticated spiro oxindole structures.