Bridged benzocyclotrimers: concepts, synthesis, and applications

Bridged polycyclic frameworks represent a unique tool to form curved units; the bicyclo[2.2.1]hepta-2,5-diene system is widely exploited to design and induce concave topologies. In particular, bridged benzocyclotrimers (BCTs) are characterized by a flat aromatic base decorated with bridged polycyclic motifs, which provide the suitable curvature underlying the concave-convex topology. In the 1960s, these molecules attracted interest for their own chemical and physical properties. Later, the improvements in synthetic procedures to produce bridged BCTs have paved the way for their utilization to design and prepare molecular containers, bowls, cages, and baskets that are able to accommodate target molecules, recognize them, and modulate their functions. In this frame, we aim to describe the historical evolution of the concept, from the first bridged BCTs explored to confirm the existence of strained alkynes, and the phenomenon of bond alternation (Mills-Nixon hypothesis), to the most recent gated molecular baskets developed as dynamic synthetic receptors for molecular delivery. The main synthetic approaches which have been used to perform cyclotrimerization of bridged polycyclic alkenes, and related mechanisms, are also examined and discussed, with a specific focus on the syn/anti stereoselectivity issue and its consequences at a mechanistic level. The present review covers literature contributions published until mid 2021.