London Dispersion Favors <i>Cis</i> Selectivity in the Johnson–Corey–Chaykovsky Epoxidation

We elucidate the role of dispersion energy donors on the <i>cis</i>/<i>trans</i> selectivity of the Johnson-Corey-Chaykovsky epoxidation, focusing on bulky alkyl groups as well as halides as dispersion energy donors. Whereas the generally accepted explanation of the observed diastereoselectivity solely invokes steric repulsion, we determined that London dispersion interactions are an important source of stabilization of the preferred transition structures. This was brought forth experimentally by utilizing a series of NMR measurements, double mutant cycles, and crossover experiments. Additionally, density functional theory computations and symmetry-adapted perturbation theory computations were used to determine and quantify the role of noncovalent interactions.