Halogen bond-catalyzed Friedel-Crafts, Povarov and aziridine ring-opening reactions

Abstract

Chapter 1: Halogen bonds have been studied and applied in many fields, the use of halogen bonding in the field of organocatalysis has only been reported in recent years. Currently, only dozens of examples related to halogen bond catalysis were reported by several research groups. The electrophilic region in the halogen atom of the halogen bond was well explained by the σ-hole theory in the past decades, other features derived from the σ-hole theory such as tunability, directionality, and nuclear magnetic resonance (NMR) chemical shifts were explained and applied in halogen bond catalysis. Chapter 2: Inspired by the interesting characters of the halogen bond and limited reports of halogen bond catalysis, a synthetically challenging benzimidazole-based cationic bidentate halogen bond donor catalyst was strategically designed and successfully synthesized. The catalyst has been successfully applied in the Friedel-Crafts reaction in the formation of bis(indolyl)methanes as a new conceptual type of catalyst. Natural compounds such as arsindoline A, trisindoline, arundine, and vibrindole A with interesting bioactivities were synthesized in high yields using the halogen bond donor catalyst. Chapter 3: The designed halogen bond donor catalyst was also used to catalyze the Povarov reaction, which fills the knowledge gap of halogen bond catalysis both in the normal electron demand Diels-Alder reaction and the inverse electron demand Diels-Alder reaction. The methodology shows advantages over other commonly used catalysts, including mild reaction conditions, shorter reaction time, and wide substrate tolerance both in dienes and dienophiles. Different halogen analogues were synthesized to prove halogen bonding was indeed operative in the Povarov reaction. Chapter 4: The concept of halogen bond catalysis was successfully extended in the aziridine ring-opening reaction with high yields and regioselectivities. Hidden acids and radical mechanisms were successfully ruled out by a series of control reactions. The notion of halogen bond catalysis was also demonstrated by NMR spectroscopy analysis. Overall, the halogen bond donor catalyst was successfully designed and applied in various reactions with strong advantages as compared to conventional catalysts known in this field.