Influence of intramolecular interactions and transition state energetics on the strain-promoted azide–alkyne cycloaddition of 2-aminobenzenesulfonamide-containing cyclononynes

Abstract

Computational investigation of the reaction mechanism and selectivity of strain-promoted azide–alkyne cycloaddition indicated that 2-aminobenzenesulfonamide-containing cyclononyne (ABSACN) is a HOMO donor; the energy difference is slight between the transition states (TSs) for the major and minor products. The reaction between unsubstituted ABSACN(R¹R²H) and benzyl azide proceeds via the pathway that is most energetically favorable, minimizing the influence of steric repulsion, intermolecular interactions, and the strain energy of ABSACN. In the case of R¹Boc, the intramolecular hydrogen bond is maintained in both the X-ray-characterized minor product and its corresponding transition state, and the calculated product ratios coincided with the experimental data.