Structure–reactivity relationships in a recognition mediated [3+2] dipolar cycloaddition reaction

The [3+2] dipolar cycloaddition between an azide and maleimide can be accelerated by a factor of more than 100 simply by attaching complementary recognition sites to the reactive partners. This rate acceleration derives from the formation of a reactive binary complex between the azide and the maleimide. The variation of the observed rate acceleration with simple structural changes, such as adding additional rotors, should be relatively predictable. However, the application of a simple, rotor-based increment in the systems reported here is insufficient to predict reactivity correctly. Computational studies suggest that the nature of the available reaction pathways within the binary complex formed by the reactants is important in determining the reactivity of a given complex.