The intramolecular cyclization of 5-hexenyl radicals continues to be an important synthetic method for the construction of five-membered rings. The synthetic utility arises from the high degree of regioselectivity to give predominantly cyclopentyl products in high yield under mild conditions. Recently we reported product cyclization studies on 4-oxa perturbed 5-hexenyl radical. In this paper we report our results from a computational study (UB3LYP and UCCSD(T)) of the cyclization of a series of 5-hexenyl and 3- and 4-oxa-5-hexenyl radicals. Three highly conserved cyclization transitions states (exo-chair, exo-boat and endo-chair) were located for 10 acyclic radicals. Activation en-ergies were calculated for the three modes of cyclization for each radical. Calculated values for the exo/endo cycliza-tion ratios had a high level of agreement with experiment and predictions were offered for two cases that have not been experimentally tested. The increased percentage of exo-cyclization with 3- and 4-oxa substitution is the result of an increase in the energy difference between the exo- and endo-chair transition states compared to the hydrocarbon sys-tems. The decreased rate of cyclization of the 4-oxa compounds is primarily due to the stabilization of the initial acy-clic radical by the vinyl ether linkage. The increase in the rate of cyclization with 3-methyl substitution is due to the increased conformational energy of the starting acyclic radical.
Matlin, Albert R. and Matthew C. Leyden. 2013. “Computational Study of the Cyclization of 5-Hexenyl, 3-Oxa-5-hexenyl and 4-Oxa-5-hexenyl Radicals.” International Journal of Organic Chemistry 2013(3): 169-175.
Scientific Research Publishing
International Journal of Organic Chemistry
Chemistry and Biochemistry
Radical cyclizations, Activation energies, UB3LYP, UCCSD (T)