General Synthesis and Properties of Bridged, Fused, and Spirocyclic Azacycles via Intramolecular C–H Bond Amination

General methods to construct complex azacycles significantly enable the invention of new therapeutics. Herein, we describe a unified strategy to access bridged, fused, and spirocyclic bicyclic azacycles leveraging a Hofmann-Löffler-Freytag (HLF) approach. Our method yields value-added and complexity-enriched amines through an intramolecular C–H bond functionalization, converting monocyclic amines to bicyclic amines in a single step. Depending on the connectivity between the amine and the monocyclic ring, we are able to access bridged, fused, and spirocyclic architectures. Additionally, the physicochemical properties of these bicyclic amines were evaluated, and it was found that bridged amines tend to be less lipophilic in comparison to their monocyclic matched pairs.