Selective spontaneous reaction of flavonoids in CD-MOF-1

Developing artificial reactors for the synthesis of peroxy (O-O) bonds offers a new route to the creation of flexible intermediate platforms. Herein, we report a selective spontaneous reaction of flavonoid with γ-cyclodextrin (γ-CD) in cyclodextrin metal-organic framework (CD-MOF-1). Remarkably, simple incubation of flavonoids within CD-MOF-1 at ambient conditions in the dark leads to the spontaneous formation of an O-O bond between flavonoid and γ-CD. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nuclear magnetic resonance (NMR) results confirm that the isolated flavonoid-γ-CD compounds involve O-O bonds and preferentially form at the hydroxyl in the flavonol C ring (<i>e.g.</i>, quercetin) or at the <i>meta</i>-phenol hydroxyl on the flavone B ring (<i>e.g.</i>, epigallocatechin gallate, EGCG). Intriguingly, flavonoids bearing both <i>meta</i>- and <i>para</i>-hydroxyl groups in the B ring (<i>e.g.</i>, EGCG) or those with an adjacent carbonyl on the C ring (<i>e.g.</i>, quercetin) underwent this reaction, whereas flavonoids lacking these features (<i>e.g.</i>, taxifolin, luteoline, apigenin, naringenin, hesperetin and daidzein) cannot trigger this reaction. Density functional theory (DFT) calculations indicate that potassium (K⁺) cations in the CD-MOF-1 reduce the bond dissociation energies (BDEs) of the relevant hydroxyl groups, catalyzing O-O bond formation. This work reveals that CD-MOF-1 can orchestrate the precise arrangement of reactants and activate their specific sites, enabling selective O-O bond formation under mild and dark conditions. We expect this discovery to encourage further development of CD-MOF-1-based platforms for mild, selective oxidative transformations and the generation of novel intermediates.