New Method Development to Streamline the Synthesis of N-Heterocycles

Nitrogen-heterocycles are an important class of molecules because of its widespread availability in pharmaceuticals, natural products and organic electronic materials. Significant research efforts have been made to construct complex N-heterocycles starting from simple organic molecules. The research program in the Driver lab is focused on exploiting the reactivity of metal N-arylnitrene intermediates to create heterocycles. Our group has successfully used aryl azides as a nitrogen-atom source to create C–N bonds from sp3-C–H bonds or sp2-C–H bonds. The construction of C–N bonds through domino electrocyclization-migration reactions were discussed in the first chapter. In the second chapter the reactivity of styryl azides was investigated to perform an electrocyclization, selective aminomethylene migration reaction. An efficient synthesis of styryl azides was described in the third chapter and use of these styryl azides were demonstrated by converting them into indole derivatives. In the fourth chapter, the reactivity of metal nitrene intermediates toward C–H bond amination or electrocyclization reactions were examined in order to derive a general trend of reactivity of aryl azides. In the following chapters, we demonstrated that a similar reactivity pattern of aryl azides could also be accessed from nitroarenes. In chapter five, we demonstrated that the reactivity of tetrasubstituted nitroarenes toward a cyclization-migration reaction could be unlocked by a palladium(II)-catalyst and Mo(CO)6. In the final chapter, we showed the potential of nitroarenes to undergo a sp3-C–N bond formation by reductive cyclization reaction to afford indolines.