RESUMO
The reaction pathway of silyloxypyrone-based (5 + 2) cycloadditions was determined to be extremely dependent on the nature of the dipolarophile. Neutral alkenes were the least reactive, whereas both electron-deficient and electron-rich dipolarophiles were more reactive, thus providing evidence for ambident oxidopyrylium intermediates. Qualitative rate studies, Hammett linear free energy relationships, and theoretical calculations combined to provide evidence for a spectrum of reactivity that passes through the borderlands of concerted and stepwise.
RESUMO
Silyloxypyrone-based (5+2) cycloadditions were facilitated by amides that allowed for increased reactivity and a pathway for cleaving the tether to afford net intermolecular cycloadducts. Various amides underwent facile cycloaddition, and several experiments revealed steric and electronic factors that accelerate the reaction. tert-Butyl amides reacted faster than less hindered variants in multiple cases. In the case of dearomative oxidopyrylium-indole (5+2) cycloadditions, an amine-based tether was ineffective, whereas amides enabled this powerful transformation. Theoretical calculations evidenced a concerted asynchronous reaction in which the amide facilitates a conformational driving force enabling cycloaddition. Finally, a one-pot acylation/(5+2) cycloaddition/nucleophilic lactam opening and other examples of tosyl lactam opening of a modified cycloadduct were demonstrated.