Study of the Mechanism of 7-exo-trig Cyclizations of Aryl, Vinyl, and Alkyl Radicals on Oxime Ethers

In this work, we conducted a study of 7-exo-trig cyclizations mechanism involving aryl, vinyl, and alkyl radicals on oxime ethers. Initially, the reaction of brominated oxime ether 9 a with (TMS)₃SiH and AIBN gave rise to aryl radicals that underwent a 7-exo-trig cyclization on the oxime ether, yielding dibenzoxepine 10 a, and the ipso reaction and reduction products were obtained as well. Approximate rate constants at 80 °C for the 7-exo-trig (1.0×10⁸ s⁻¹) and the ipso cyclization (4.3×10⁷ s⁻¹) were determined by competition experiments. DFT calculations showed good agreement with the experimental results. The reduction rate constant of the N-alkoxyaminyl radical with (TMS)₃SiH was calculated to be 4.1×10⁻¹ M⁻¹ s⁻¹; while the rate constants for the 7-exo-trig cyclizations of vinyl and alkyl radicals on the oxime ether were estimated in the ranges of 10⁶ s⁻¹–10⁸ s⁻¹ and 10³ s⁻¹–10⁸ s⁻¹, respectively. The 7-exo-trig cyclization reactions involving aryl, vinyl, and alkyl radicals with oxime ethers were found to be an exothermic and irreversible process, with the oximic carbon showing a preference for nucleophilic alkyl radicals. This kinetic study contributes to the deeper understanding of radical-mediated cyclizations, enabling the efficient design of complex synthetic routes.