In recent years, the incorporation of greater saturation into pharmaceutical leads has become a major focus within drug discovery. It has been shown that increasing the sp<sup>3</sup> character within a drug’s core often correlates to lower toxicity, leading to greater potential for advancing through clinical trials and approval. The 2-azanorbornane scaffold has been identified as a more rigid alternative to piperidine and pyrrolidine functionality within pharmaceuticals. In addition to this bioisosterism, this motif allows for a greater degree of possible substitution patterns, and derivatives of these scaffolds have been demonstrated as ligands for asymmetric transformations.<br/><br/>Bicyclic systems of this sort are particularly underexplored in medicinal chemistry and drug discovery. The synthesis of structurally complex 2-azanorbornanes has proven to be challenging for synthetic organic chemists, with the most precedented routes relying on thermally initiated aza-Diels-Alder reactions. The need to develop orthogonal approaches is critical due to the drawbacks and limitations associated with these strategies. Photochemical mediated processes offer a welcome alternative to these existing strategies, with previous studies in our lab detailing radical cascade reactions towards saturated bicycle synthesis. Herein, we describe adaptation of this protocol towards 2-azanorbornane synthesis, harnessing the power of the strain-driven homolysis of amine-radical-cations under mild conditions.

Photochemical approach to novel 2-azanorbornanes

ACS Fall 2021

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