Distance-Dependent, Rate-Accelerating and Diastereoselective Directing Effects in Decatungstate-Mediated Stereoediting Reactions

The excited-state decatungstate (DT) polyanion is an important and commonly used hydrogen atom transfer (HAT) reagent in organic synthesis. The intrinsic site- and diastereoselectivity of DT-mediated HAT steps is broadly accepted as being dictated by steric and bond polarity (mis)matching effects, and DT's rigid polyoxometalate structure presents limited opportunities for altering this reactivity profile. Here, we reveal that innate functional groups, such as secondary amides, can accelerate the rate of HAT by DT in a proximity-dependent and diastereoselective manner. We leverage this directing effect to access cis-1,2-disubstituted amides via the contra-thermodynamic C-H epimerization of readily obtained trans-configured starting materials. The discovery that noncovalent interactions can be used to guide the reactivity of excited-state DT fundamentally transforms our understanding of this reagent's control paradigms, opening the door to the design of new strategies to tune the selectivity of DT-mediated HAT steps.