Relative kinetic data were determined for the 5- endo- trig cyclization of radical 12 compared to hydrogen abstraction from (TMS)3SiH in the temperature range of 344-430 K, which allows for the estimation of a rate constant of 2 x 10(4) s-1 at 298 K with an activation energy of ca. 9 kcal/mol for the cyclization process. The 5- endo- trig cyclization of a variety of radicals that afford five-membered nitrogen-containing heterocycles was addressed computationally at the UB3LYP/6-31G* level. The 5- endo vs 4- exomode of cyclication and the effect of delocalization of the unpaired electron in the transition state were investigated. Because the ring formed during cyclization contains five sp2 centers, electrocyclization via a pentadienyl like resonance form was also considered. For comparison, similar calculations were performed for 4-penten-1-yl and related radicals. The factors that affect the activation energies of homolytic 5- endo- trigcyclization were determined. In the absence of steric or conformational effects, the endocyclization to form the five membered ring was strongly favored over exo cyclization to form the four-membered ring not only on thermodynamic grounds but also kinetically. When a substituent on the double bond was able to delocalize the unpaired electron in the transition state of the 4- exopath, the two modes of cyclization became kinetically comparable. These results have an important bearing on the generalization of the Baldwin-Beckwith rules, which classified the 5- endo- trig radical cyclization as a disfavored process.
5-endo-trig radical cyclization:disfavored or favored processes?
Chatgilialoglu C;Ferreri C;Guerra M;
2002
Abstract
Relative kinetic data were determined for the 5- endo- trig cyclization of radical 12 compared to hydrogen abstraction from (TMS)3SiH in the temperature range of 344-430 K, which allows for the estimation of a rate constant of 2 x 10(4) s-1 at 298 K with an activation energy of ca. 9 kcal/mol for the cyclization process. The 5- endo- trig cyclization of a variety of radicals that afford five-membered nitrogen-containing heterocycles was addressed computationally at the UB3LYP/6-31G* level. The 5- endo vs 4- exomode of cyclication and the effect of delocalization of the unpaired electron in the transition state were investigated. Because the ring formed during cyclization contains five sp2 centers, electrocyclization via a pentadienyl like resonance form was also considered. For comparison, similar calculations were performed for 4-penten-1-yl and related radicals. The factors that affect the activation energies of homolytic 5- endo- trigcyclization were determined. In the absence of steric or conformational effects, the endocyclization to form the five membered ring was strongly favored over exo cyclization to form the four-membered ring not only on thermodynamic grounds but also kinetically. When a substituent on the double bond was able to delocalize the unpaired electron in the transition state of the 4- exopath, the two modes of cyclization became kinetically comparable. These results have an important bearing on the generalization of the Baldwin-Beckwith rules, which classified the 5- endo- trig radical cyclization as a disfavored process.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
