Our research is directed towards the development of new methods that increase the structural complexity of readily available substrates. Currently, we are interested in developing new transition metal-mediated reactions, which transform azides into N-heterocycles.

N-Heterocycles

N-Heterocycles are important molecules found in pharmaceuticals, materials, and natural products (Scheme 1). Their ubiquity continues to inspire organic chemists to design new methods, which enable access to them. One attractive solution for the synthesis of these componds is C–H bond amination because it enables new bond formation without the manipulation of functional groups. In principle, achieving more efficient routes to these architectures should lower the cost of the final product.


Scheme 1. A few pharmaceutical N-heterocycles.

We anticipated that these N-heterocycles could be synthesized from azides (Scheme 2) or nitroarenes (Scheme 3). The use of these precursors in the construction of these important compounds remains underdeveloped due to the harsh conditions necessary to unlock their reactivity. We have found that transition metals can catalyze C–H bond amination reactions to facilitate access to these N-heterocycles.


AZIDES

Using transition metal catalysts, we have successfully constructed a range of N-heterocycles, including indoles, carbazoles, pyrroles, benzimidazoles, and indolines, whose motifs are prevalent in biologically relevant small molecules (Scheme 2). In addition to the development of new methods, we are also interested in studying the mechanisms of these transformations.

Pasted Graphic
Scheme 2. Transition metal-catalyzed N-heterocycle formation from azides.

NITROARENES
Similar reactivity patterns can be accessed from nitroarenes using transition metals to generate electrophilic N-aryl metal intermediates (Scheme 3). Using nitroarenes addresses the step-inefficient substrate syntheses and safety considerations of using an azide as the N-atom precursor.

Pasted Graphic 1
Scheme 3. Unlocking and controlling the reactivity embedded in nitroarenes with palladium.