Transition‐Metal‐Catalyzed Cycloadditions for the Synthesis of Eight‐Membered Carbocycles

Eight-membered carbocycles are found in a wide variety of natural products that exhibit a broad range of biological and medicinal activities (cf. the most potent anticancer drug, taxol). However, the synthesis of eight-membered carbocycles is quite challenging as traditional approaches are met with entropic and enthalpic penalties in the ring-forming transition states. These negative effects can be totally or partially avoided with the implementation of transition-metal-catalyzed/mediated cycloadditions. In this Focus Review, examples of elegant and efficient metal-catalyzed and some metal-mediated cycloadditions (including Ni- catalyzed 4+4 and Rh-catalyzed 4+2+2 and 5+2+1 reactions) are presented to illustrate this. Application of these cycloaddition reactions in total synthesis is also presented to show the significance of these reactions in addressing challenges in natural product synthesis.