(3 + 2) cycloaddition reaction of 7-isopropylidenebenzonorbornadiene and diazomethane derivatives: A theoretical study.

The ability to synthesize targeted molecules hinges on detailed mechanistic insight of the reaction. The 1,3-dipolar cycloaddition reaction between diazomethane derivatives and 7-isopropylidenebenzonorbornadiene have been extensively studied using density functional theory (DFT) at the M06-2X/6-311G(d,p) level of theory in order to delineate the peri-, regio-, and stereo-selectivities of the reaction. The diazomethane is shown to periselectively add across the endocyclic olefinic bond of the 7-isopropylidenebenzonorbornadiene and stereoselectively in the exo fashion, yielding the exo-cycloadduct as the major product, with a rate constant of 3.83 × 10 s. The endo approach of this periselective path is the closest competing pathway with a rate constant of 8.78 × 10 s. Neither electron-donating groups (R = methyl, ethyl, amine, cyclopropyl) nor electron-withdrawing groups (R = cyano, nitro, carbonyl) on the diazomethane alters the peri- and stereo-selectivity of the reaction. However, the substituents do have an effect on whether the addition follow normal or inverse electron demand mechanisms. EDGs favor a normal electron demand mechanism while EWGs favor an inverse electron demand 1,3-dipolar cycloaddition reaction. While EDGs-substituted diazomethane derivatives behave as nucleophiles in reactions with 7-isopropylidenebenzonorbornadiene, EWGs-substituted diazomethane derivatives behave as electrophiles. The 1,3-dipole adds across the dipolarophile via a concerted asynchronous mechanism, but a stepwise diradical mechanism has been ruled out. The selectivities observed in the title reaction are kinetically controlled. Analysis of the nucleophilic Parr function (P) at the different reaction sites in the dipolarophile indicates that the diazomethane adds across the atomic centers with highest NBO and Mulliken atomic spin densities.