Higher-Order Electrocyclizations in Biological and Synthetic Processes

In general, electrocyclizations follow the Woodward-Hoffmann's rules of conservation of orbital symmetry. These rules have been extensively verified in low-order processes, both in thermal and photochemical reactions, up to eight pi-electrons. However, when the number of pi-electrons in the system increases, some deviations of that general rules can be found. This focused review highlights the main features of reported higher-order electrocyclizations involving 10, 12, 14, 16 and 18 pi-electrons. Some of these examples constitute useful intermediates in the synthesis of biologically active compounds. When computational studies were not included in the reported examples, DFT calculations have been performed to be included in this review. Analysis of the respective pericyclic topologies shows the importance of computational tools for understanding the selectivity observed experimentally. Beyond n=1: This focused review describes 10 pi-18 pi electrocyclizations reported in the literature. The use of these processes for the synthesis of complex cyclic scaffolds is also briefly described. DFT mechanistic analysis of the reported pericyclic reactions are discussed. It was found that, for some of these reactions, the Woodward-Hoffmann rules for thermal electrocyclizations are not followed.image