Double Duty Synthons in Epoxide Synthesis and Palladium-Catalyzed Carbonylative Heterocyclizations

The concept of double duty presumes incorporation of two traditionally distinctly reacting parts of a chemical into one transformation. The first example of the double duty reactivity was demonstrated by using haloalkynes as a combination of both acetylide and electrophilic halogen in highly efficient transformations of ketones into density substituted alkynyl epoxides. During the course of research, we were able to demonstrate the double duty reactivity of cyanogen bromide and bromopolyfluoroarenes in highly efficient transformations of enolizable ketones into densely substituted epoxides via an electrophilic α-bromination/nucleophilic addition/nucleophilic substitution cascade reaction. This method allows for synthesis of valuable divergently substituted epoxides. C2-substituted indolizines, particularly those possessing electron-withdrawing groups, are interesting synthetic targets with great potential for biological activity study. However, there are no efficient and general approaches toward these molecules. We successfully developed the palladium-catalyzed synthesis of 2-aroyl indolizines from aryl iodides and readily available propargyl pyridines under carbon monoxide atmosphere. This general method allows for efficient synthesis of divergently substituted 2-aroyl indolizines under benign reaction conditions.