The ability to make precise alterations to the carbon skeletons of molecules is a central point of focus in organic synthesis. Such transformations are complicated by the inherent inertness of carbon-carbon (C–C) bonds. C–C bond activation seeks to utilize these ubiquitous but typically inert bonds as direct sites of reactivity in a precise manner, thereby opening the door to new and unconventional retrosynthetic disconnections. The transition metal-catalyzed “cut-and-sew” C–C activation reaction achieves this feat through direct insertion of an unsaturated unit into a C–C bond of a cyclic ketone to rapidly build up molecular complexity. In this system, a metal first undergoes oxidative addition into a C–C bond. An unsaturated compound then ligates to the resulting metallacycle. A series of migratory insertion and reductive elimination steps then furnish a ring expansion product via the precise insertion of an unsaturated compound into a C–C bond. This transformation enables swift access to new chemical space based on the identity of the unsaturated unit utilized. While various pi bonds have been applied to this chemistry, they are most often stable, carbon-based units. To expand the versatility of the “cut-and-sew” C–C activation reaction and the chemical space to which it can afford access, various pi systems were explored with a focus on strained, fleeting intermediates and heteroatom-rich pi systems. To this end, a palladium-catalyzed “cut-and-sew” reaction of arynes with benzocyclobutenones was successfully developed, enabling incorporation of arene moieties into the carbon skeletons of substrates. Mechanistic studies were carried out through various means which support a traditional “cut-and-sew” mechanism of aryne insertion into C–C bonds. The application of 2,3-heteroarynes to the “cut-and-sew” C–C activation reaction was also investigated and ultimately, a transition metal-free formal insertion of 2,3-heteroarynes into the C–C bonds of benzocyclobutenones was achieved. Various studies indicate a novel base-mediated C–C activation process to be operative. This reaction enables access to annulated indole, azaindole, benzofuran, and benzothiophene scaffolds in a modular fashion. Finally, the use of N=N double bonds towards the “cut-and-sew” C–C activation process was studied using diazene-tethered cyclobutanones. An unexpected Lewis acid-catalyzed C–C activation process was ultimately realized which enables access to a unique class of semi-saturated polycyclic N-heterocycles. These endeavors which initially sought to expand the scope of the “cut-and-sew” C–C activation reaction have led to the development of new methods for making alterations to the carbon skeletons of strained cyclic ketones and have expanded the chemical space accessible through this chemistry while revealing novel mechanisms for C–C bond scission in some cases.
