Higher-order cycloadditions in the age of catalysis

Summary Classical cycloaddition reactions are highly atom-economical reactions toward cyclic systems, often proceeding with impressive efficiency and selectivity. Still, the development of higher-order cycloadditions (HOCs), which involve rehybridization of >6π-electrons, have presented more pronounced challenges due to the necessity of employing extended, more reactive cycloaddends. Catalytic generation of such π-systems allows for their controlled, enantioselective usage, and organocatalysis has in recent years proven a potent tool in this regard. Here, hitherto successful organocatalytic HOCs are classified based on the generated cycloaddends, and the factors that play a crucial role to the feasibility of their formation and usage are analyzed. For these reactions, aminocatalysis remains the most applied activation strategy, and the lessons obtained therefrom may provide a foundation for the elaboration of other organocatalytic strategies, of which sporadic examples demonstrate the potential for the continued growth of catalytic HOCs as a field.