Computational study on the mechanism of the reaction of benzenesulfonyl azides with oxabicyclic alkenes.

Abstract

The reaction of benzenesulfonyl azides with oxabicyclic alkenes to form aziridines could either proceed via initial [3 + 2] cycloaddition to form triazoline intermediates which then leads to aziridines, or via initial dinitrogen cleavage of the benzenesulfonyl azide to afford a nitrene intermediate followed by addition of this nitrene species across the olefinic C-C bond of the oxabicyclic alkene. Calculations at the DFT M06-2X/6-311G(d,p) level indicate that the initial [3 + 2] cycloaddition reaction of benzenesulfonyl azide and oxabicyclic alkene has barriers of 15.0kcal/mol (endo) and 10.3kcal/mol (exo) and rate constants of 5.23 × 103s-1 (endo) and 3.86 × 106s-1 (exo) whereas the pathway involving initial formation of nitrene species has a high activation barrier of 39.2kcal/mol and rate constant of 8.92 × 10-12s-1, indicating that the reaction will go through the former route to form an exo triazoline intermediate. The exo triazoline can either undergo a concerted C-C, N-N bond cleavage to form a ring-opened intermediate, a reaction that has a barrier of 23.4kcal/mol, followed by dinitrogen extrusion and C-C, C-N bond regeneration with barriers of 29.1 and 23.5kcal/mol respectively to form endo aziridines, or it can undergo direct nitrogen extrusion to form the exo product, a reaction with a barrier of 38.3kcal/mol. Since the rate-determining step of the former route is 9.2kcal/mol more favored than the latter, the former route rate is favored. The rate constants of the rate-determining steps are 1.30 × 10-5s-1 (endo) and 3.16 × 10-11s-1 (exo), indicating that endo aziridine would be formed as the major product and this is in conformity with the experimental observations of Chen et al. (J. Org. Chem. 18:11863-11872, 2019). The position of substituents on the benzene group of the benzenesulfonyl azide affects the endo/exo diastereoselectivity.Graphical abstract.