Triply Hydrogen-Bond-Directed Enantioselective Assembly of Pyrrolobenzo-1,4-diazine Skeletons with Quaternary Stereocenters

Highly efficient synthesis of optically enriched pyrrolobenzo-1,4-diazines bearing quaternary stereocenters has been realized through the chiral BrOnsted acid-catalyzed Pictet-Spengler reaction of 2-(1H-pyrrol-1-yl)anilines and -ketoamides in good to excellent yields and enantioselectivities. Computational studies suggest an unprecedented phenomenon whereby the chiral phosphoric acid catalyst employs attractive arene CHN hydrogen bonding to activate the substrate and induce chirality through a triple hydrogen-bonding interaction.