Nitrogen-bridgehead compounds: overview, synthesis, and outlook on applications

The nitrogen-bridgehead is a common structural motif present in a multitude of natural products. As many of these abundant compounds exhibit biological activities, e.g. against cancer or bacteria, these derivatives are of high interest. While natural products are often associated with problematic characteristics, such as elaborate separation processes, high molecular complexity and limited room for derivatization, purely synthetic approaches can overcome these challenges. Many synthetic procedures have been reported for preparation of artificial nitrogen bridgehead compounds, however, to our surprise only a fraction of these has been tested for their bioactivity. This review is therefore meant to give an overview of existing synthetic methods that provide scaffolds containing bridgehead nitrogen atoms, covering the period from 2000 to 2023. Reviews which cover subunits of this topic are referenced as well.