Strategies for the Construction of Benzobicyclo[3.2.1]octane in Natural Product Synthesis

Benzobicyclo[3.2.1]octane is a cage‐like unique motif containing a bicyclo[3.2.1]octane structure fused with at least one benzene ring. It is found in various natural products that exhibit structural complexities and important biological activities. The total synthesis of natural products possessing this challenging structure has received considerable attention, and great advances have been made in this field during the past 15 years. This review summarizes thus far achieved chemical syntheses and synthetic studies of natural compounds featuring the benzobicyclo[3.2.1]octane core. It focuses on strategic approaches constructing the bridged structure, aiming to provide a useful reference for inspiring further advancements in strategies and total syntheses of natural products with such a framework. The total synthetic strategies for 11 complicated natural products containing (di)benzobicyclo[3.2.1]octane motif are reviewed as well as the synthetic studies on model compounds and analogs. The reaction types for the key cyclization step include Friedel–Crafts, aldol, and cascaded combination of similar processes.