Iodo imidazolinium Catalyzed Reduction of Quinoline by Hantzsch Ester: Halogen Bond or Bronsted Acid Catalysis.
Halogen bond (XB) catalyzed reactions could also be catalyzed by Bronsted acids, which may complicate the picture of the true activation pathway for these reactions. Herein, we report the first density functional theory (DFT) study of the mechanistic pathways for the uncatalyzed, iodoimidazolinium halogen bond catalyzed, and a competitive Bronsted acid catalyzed reduction of quinoline by Hantzsch ester. The uncatalyzed reaction was found to proceeds via stepwise pathways. In the lowest energy pathway, proton transfer from Hantzsch ester, a weak Bronsted acid, to quinoline prior to hydride reduction was identified as the key to the lowered energy compared to other pathways. The same reaction steps are involved in the XB catalyzed pathway, but with substantially lowered reaction barriers, particularly for the hydride transfer steps. In contrast to general belief that halogen bond catalysts bind to the electrophile quinoline and activate it through lowering its LUMO energy, we discovered that it is preferable to lower the LUMO energy of quinoline through protonation by Hantzsch ester as a Bronsted acid and stabilize the conjugate anion of Hantzsch ester via halogen bond. Finally, our calculations reveal that iodoimidazolinium type of catalyst is prone to reduction by Hantzsch ester, generating a Bronsted acid as product. The Bronsted acid catalyzed pathway was calculated to be competitive to the halogen bond catalyzed pathway. Our theoretical findings highlight the need to be cautious when applying iodoimidazolinium catalysts in organocatalysis and we hope it will aid the design of new halogen bond catalysts that could avoid undesirable Bronsted acid catalysis.
The Journal of organic chemistry