Chiral Spirocyclic Phosphoric Acid-Catalyzed Asymmetric Synthesis Of4,5-Dihydropyrrolo[1,2-α] Quinoxaline

As an important class of nitrogen-containing heterocyclic compounds, quinoxaline derivatives have attracted considerable attention of chemists and pharmacists because they have been found to act as antibacterial, antitumor, antituberculosis and antidepressive agents. In this thesis, the progress of the asymmetric Pictet-Spengler reaction is reviewed firstly. Then, we study the asymmetric synthesis of quinoxaline derivatives with chiral quaternary sterocenters, which is catalyzed by chiral spirocyclic phosphoric acids (SPAs) invented by our group. The results are listed:A highly enantioselective synthesis of4,5-dihydropyrrolo[1,2-a]quinoxalines catalyzed by SPAs has been developed. Under the optimal reaction conditions of (S)-6,6’-di-9-phenanthrenyl-phenyl-SPINOL-phosphoric acid, toluene,4A MS,40℃, chiral products were obtained in high yields (up to92%) with excellent enantioselectivities (up to99%) from2-(N-pyrrolyl) anilines and a-ketoamides. The absolute configuration of substrates was confirmed to be (R) by X-ray. Computational studies suggest an unprecedented phenomenon that the chiral phosphoric acid catalyst employs attractive arene C-H…N hydrogen bonding to activate substrate and induce chirality via triple hydrogen-bonding interactions, which enrichs chiral spirocyclic phosphoric acids chemistry.