Predictable Selectivity in Remote C−H Oxidation of Steroids: Analysis of Substrate Binding Mode

Abstract

Predictability is a key requirement to encompass late‐stage C−H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp3)−H oxidation, as it requires distinguishing a specific C−H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C−H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host‐guest adduct by NMR analysis. These analyses indicate which remote C−H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late‐stage C(sp3)−H oxidation of amino‐steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.

Unraveling the Origin of the Regioselectivity of a Supramolecular Hydroformylation Catalyst

“…In the past two decades, supramolecular strategies in transition metal catalysis have provided chemists a toolbox to obtain selectivity control for challenging substrates as these strategies allow for energetic differentiation among competing reaction pathways [3–13] . Indeed, applying such supramolecular strategies has led to unique and unprecedented selectivity control and thus provide a complementary tool to traditional transition metal catalysts [14–36] …”