A Host–Guest Supramolecular Approach to Boosting Consecutive Multi‐Photon Excitation for the Arylation of Inert C( <i>sp</i> ³ )─H Bonds

Biological photosynthesis harnesses multiple visible light photons to drive thermodynamically demanding reactions, whereas realizing analogous multi-photon excitation in artificial photosynthesis remains challenging. Inspired by enzymatic cascades, we herein report a host-guest supramolecular approach to boosting consecutive multi-photon excitation (>2 photons) by confining a 9-mesityl-10-methylacridinium perchlorate (Acr⁺) guest within a coordination supramolecular host assembled from triphenylamine-derived ligands (TPA) with Ce─Ot-Bu nodes for efficient inert C(sp³)─H bond activation and transformation. The composition and structure of the consecutive multi-photon excitation host-guest supramolecular system were characterized by a combination of high-resolution electrospray ionization mass spectrometry, NMR, UV-vis spectrum, fluorescence spectrum, and isothermal titration calorimetry. The multi-photon excitation host-guest supramolecular system furnished a catalytic proficiency of 50 h^-1 for the oxidative arylation of inert C(sp³)─H bond, representing an approximately 88-fold increase compared to methods employing strong oxidants or harsh acids, and obviously superior to the best previously reported more than two-photon system based on consecutive excitation at a single site. To our knowledge, this represents the first example of consecutive multi-photon excitation integrating three separated photo-responsive sites within a host-guest supramolecular system, which reaches superactivity for inert C(sp³)─H bond transformation, offering an attractive avenue toward low-energy light-driven challenging chemical transformations under mild conditions.