Modern Higher-Order Cycloadditions.

Higher-order cycloadditions, defined as pericyclic reactions involving more than 6π-electrons, have emerged as powerful and mechanistically diverse reactions that allow for the construction of larger and more complex polycyclic ring systems beyond the classical Diels-Alder reaction. This review provides a comprehensive overview of the development, scope, and fundamental principles governing higher-order cycloadditions involving 8π-18π-electrons. Key advances in transition-metal-, Lewis-acid-, organo-, and enzyme-catalyzed higher-order cycloadditions are highlighted with emphasis on how modern catalyst design enables control over periselectivity and stereoselectivity. Mechanistic insights from density functional theory, molecular dynamics, and experimental reaction designs are discussed to illustrate how higher-order cycloadditions challenge and refine modern pericyclic theory. Together, these developments showcase the growing synthetic and conceptual significance of higher-order cycloadditions in modern chemistry.