TY - JOUR
T1 - Study of the Mechanism of 7-exo-trig Cyclizations of Aryl, Vinyl, and Alkyl Radicals on Oxime Ethers
AU - Bejarano, Carlos A.
AU - Díaz, John E.
AU - Camacho, Jairo
AU - Flores-Bernal, Gustavo G.
AU - Miranda, Luis D.
AU - Mejía, Sol M.
AU - Loaiza, Alix E.
N1 - Publisher Copyright:
© 2023 The Authors. European Journal of Organic Chemistry published by Wiley-VCH GmbH.
This is an open access article under the terms of theCreative Commons Attribution Non-Commercial NoDerivs License, whichpermits use and distribution in any medium, provided the original work isproperly cited, the use is non-commercial and no modifications or adap-tations are made.
PY - 2024/2/19
Y1 - 2024/2/19
N2 - 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.
AB - 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.
KW - 7-exo-trig radical cyclizations
KW - Competition experiments
KW - DFT
KW - Oxime ether
KW - Rate constants
UR - https://doi.org/10.1002/ejoc.202301148
UR - https://www.mendeley.com/catalogue/22882249-4927-3e91-8263-923df325cfa4/
U2 - 10.1002/ejoc.202301148
DO - 10.1002/ejoc.202301148
M3 - Article
AN - SCOPUS:85182713524
SN - 1434-193X
VL - 27
SP - 1
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
IS - 7
M1 - e202301148
ER -