5-exo-trig Versus 6-endo-trig cyclization of Alk-5-enoyl radicals: The role of one-carbon ring expansion

Article abstract of DOI:10.1002/chem.19970030309

Alk-5-enoyl radicals were made to cyclize in exo and endo modes to give the corresponding cycloketone radicals, which are related through one-carbon ring expansion. Relative kinetic data were determined for the ring closure of the 2-methylhept-5-enoyl radical generated by the reaction of the corresponding phenyl-seleno ester with Bu₃SnH over the temperature range 233-323 K. The conversion to absolute rates provided Arrhenius expressions for the 5-exo-trig and 6-endo-trig cyclizations. Ab initio and semiempirical (AM1) calculations were performed on the hex-5-enoyl and hept-5-enoyl radicals, respectively, and the outcomes aided in the rationalization of the preexponential factors and activation energies. Both 1,5- and 1,6-ring closure occur via in a lower energy 'chairlike' transition state. The observed high regioselectivity is due to favorable entropic and enthalpic factors associated with the formation of the smaller ring. The stereoselectivity was higher in the 1,6-ring closure (70:30) than in the 1,5-ring closure (55:45), the trans isomer being predominant in both. For the one-carbon ring expansion studies, the radicals of interest were obtained by deoxygenation of suitable alcohols via the O-phenyl thiocarbonates with (TMS)₃-SiH. The one-carbon ring expansion in the cyclopentanone series for the secondary alkyl radicals was studied over the temperature range 343-413 K by means of free-radical clock methodology and yielded the Arrhenius expression. The rate constant was 4.2 x 10³ s^-1 at room temperature and the reverse reaction (ring contraction) was found to be at least 10 times slower. Since the intermediacy of acyl radicals can be excluded, the reaction must occur via 3-membered cyclic intermediate radicals (or transition states).