Reaction‐Based Mechanistic Investigations of Asymmetric Hetero‐Diels–Alder Reactions of Enones with Isatins Catalyzed by Amine‐Based Three‐Component Catalyst Systems

Abstract

AbstractReaction‐based mechanistic investigations were performed for the hetero‐Diels–Alder (hDA) reactions of enones with isatins that were catalyzed by an amine‐based catalyst system composed of three molecules (an amine, an acid, and a thiourea). The results indicated that the hDA product obtained from the reaction between hept‐3‐en‐2‐one and isatin using the amine‐based catalyst system was generated via a kinetically controlled [4+2] cycloaddition reaction of the in situ‐generated enamine of the enone as the diene and isatin as the dienophile. The amine of the three‐component catalyst system was essential for the catalysis and stereocontrol, but the other components of the catalyst system also played important roles. Based on the results, plausible transition states are discussed, and the system was further improved by altering the loadings of the catalyst components for faster reactions with high stereoselectivities. The three‐component catalyst systems are flexible and can be tuned to obtain better results.