Higher-order cycloaddition reactions, especially [6+4] cycloaddition reactions, have been widely applied in the construction of 10-membered rings and natural compounds. However, these reactions encounter several challenges, including achieving regio- and stereoselectivity, overcoming high activation energy barriers, and managing multiple reaction pathways. In this review, we summarize the reported on [6+4] cycloaddition reactions, highlighting various catalysts, including metal, Lewis acid, organocatalysts, and enzyme-based catalysts.

Higher-order cycloaddition reactions (CRs) are significant in providing quick access to different polycyclic and complex molecules. In particular, [6 + 4] CRs have been widely applied in the construction of 10-membered rings, bridged molecules, and natural compounds. However, these reactions encounter several challenges, including achieving regio- and stereoselectivity, overcoming high activation energy barriers, and managing multiple reaction pathways. Over the past decade, numerous catalysts have been developed to address these challenges. The present review summarizes the reported research (2000–2024) on [6 + 4] CRs, highlighting various catalysts, including metal, Lewis acid, organocatalysts, and enzyme-based catalysts.