The Effects of Substituents on the Stabilities of Bridgehead Radicals

The relative stabilities of unsubstituted bicyclic bridgehead radicals have been previously shown to be dependent primarily upon differences in strain energies between the radicals and the corresponding saturated compounds. Although substituents are known to strongly affect the stability of acyclic carbon‐based radicals, the effect of replacing at least one of the one‐carbon bridges of bicyclic bridgehead radicals with a substituent was unknown. Because of geometrical constraints imposed by the bicyclic frameworks, the bridging substituents are unable to adopt conformations that optimize their stabilizing effects. Using [2.2.1] substituted derivatives as models, we have shown that substituents exert their effects via two primary modes. First, the presence of substituents influences the extent of hyperconjugative interactions between the SOMO and properly aligned bonds as revealed by NBO calculations. Second, when the substituents are frozen into a geometry reflective of that in the bicyclic radicals, they exert a direct impact upon the radical site that can be very different from that in the corresponding acyclic compounds. Neither of these effects alone rationalizes the relative stabilities of the radicals with various substituents. However, when combined, they offer a reasonable correlation with the observed relative energies. Generally, the effect of substituents on other bicyclic frameworks appears to follow a regular pattern of stabilization versus destabilization. The effect of changing the size of the bicyclic framework while maintaining the same substituent was also investigated. Generally, the order of relative energies mirrored that of the unsubstituted all‐carbon analogs, suggesting that strain remains the primary factor in determining stability.