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

ABSTRACT 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 (&gt;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─O t ‐Bu nodes for efficient inert C( sp 3 )─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( sp 3 )─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( sp 3 )─H bond transformation, offering an attractive avenue toward low‐energy light‐driven challenging chemical transformations under mild conditions.