[5+2] Cycloaddition Reactions in Organic and Natural Product Synthesis

Kojic acid-type cycloaddition reactions yield products similar to those obtained via the perezone-type pathways, with the only difference being a bridging oxygen atom rather than a bridging carbonyl. Mechanistically, these reactions involve the formation of an oxidopyrylium ylid as the reactive intermediate, rather than a pentadienyl cation. Domingo and co-workers have performed density functional theory (DFT) mechanistic investigations of this process and determined that the energetically preferred mechanism does indeed proceed via a discrete intramolecular group transfer, followed by a rate-limiting concerted cycloaddition step. The energy difference between the two diastereomeric cycloaddition transition states is ca. 10 kcal/mol due to constraints imposed by the tether, supporting the high diastereoselectivity observed in these reactions.