Mechanistic Analysis of Intramolecular Free Radical Reactions toward Synthesis of 7-Azabicyclo[2.2.1]heptane Derivatives

The mechanisms for the formation of conformationally constrained epibatidine analogues by intramolecular free radical processes have been computationally addressed by means of DFT methods. The mechanism and the critical effect of the 7-nitrogen protecting group on the outcome of these radical-mediated cyclizations are discussed. Theoretical findings account for unexpected experimental results and can assist in the selection of proper precursors for a successful cyclization.