Inverse Electron-Demanding Diels–Alder Reactions in the Chemical Synthesis of Prenylated Indole Alkaloids Containing a Bicycle[2.2.2]diazaoctane Moiety: A Theoretical Study

The Diels–Alder reaction is believed to be a key step in the biosynthesis of prenylated indole alkaloids containing a bicycle[2.2.2]diazaoctane moiety. Many chemical syntheses of bicyclic structures by Diels–Alder reactions have been reported, but the reaction mechanism remains underexplored. We have carried out DFT calculations on both acid- and base-promoted Diels–Alder reactions in these syntheses and reveal that the reactions occur through an inverse-electron demand mechanism. We hope that the new mechanism is helpful for the mechanistic understanding of the biosynthesis of this class of important natural products.