Host–Guest Mismatch Enables Selective Hydrogen Atom Transfer

Abstract

ABSTRACT Endogenous binding of molecular guests inside cavities of their hosts has been routinely utilized in enzymatic and supramolecular catalysis. In contrast, exogenous binding‐where a guest selectively associates with the exterior surface, rather than the cavity, of its host owing to their size mismatch‐remains a largely unexplored paradigm for controlling the selectivity of chemical reactions. Here, we report that the exogenous binding between natural cyclodextrins (CDs) and a polyoxometalate catalyst leads to high site‐selectivity in hydrogen atom transfer between them. The decatungstate anion (W 10 O 32 4– ), a photoactive polyoxometalate capable of abstracting hydrogen atoms from C–H bonds on organic molecules, was found to associate noncovalently with CDs in aqueous solution. The large size of W 10 O 32 4– , however, precludes the formation of deep inclusion complexes and confines its interactions with the narrow rim of CDs, as evidenced by 1 H NMR titration and x‐ray crystallography. This exogenous association increases the effective local concentration of W 10 O 32 4– near the C6–H bonds, accelerating HAT at these positions upon photoexcitation and rendering C6 functionalization kinetically dominant over slower, less selective background pathways. The host‐guest mismatch approach offers a general platform for the selective, one‐step ligations of CDs onto natural products, drugs, fluorescent probes as well as “click” compatible molecular scaffolds.