Host-Guest Charge-Transfer Mediated Photoredox Catalysis Inside Water-Soluble Nanocages

ConspectusVisible-light-mediated photoredox catalysis, rejuvenated by David MacMillan in 2008 following the early work by Richard Kellogg and Shunichi Fukuzumi on photosensitized reactions, has been used as an efficient strategy to carry out complex organic synthesis under mild reaction conditions. The main motivation for using visible-light during selective photoredox transformations is to minimize the use of high-energy and chemically disruptive UV-photons, thereby mimicking natural photosynthesis. Transition metal-based photosensitizers with substantial visible-light absorption cross sections and long triplet excited-state lifetimes have been successfully used to efficiently drive such light-mediated chemical transformations in organic solvents. An alternate approach for executing visible-light-mediated photocatalysis uses the idea of establishing stable donor-acceptor charge-transfer (CT) interactions, as demonstrated in 2013 by Melchiorre and co-workers, who utilized CT-based catalysis to carry out stereoselective C-C coupling reactions in bulk organic solvents. In general, most contemporary photocatalytic organic transformations in bulk solvents proceed via diffusion-limited processes, typically using triplet states. However, if the excitation energy transfer (EnT) and/or electron transfer (ET) are not temporally ordered with optimal timescales for reactive collisions driven by diffusion, photon-energy utilization will be low, due to which high-power light sources are usually applied. Therefore, engineering preorganized donor-acceptor interfaces capable of ultrafast photochemistry for catalytic transformation in water would revolutionize the photoredox paradigm while mimicking natural enzymes.This Account focuses on our efforts since 2014 to develop visible-light-driven host-guest CT state-mediated photoredox catalysis within water-soluble supramolecular nanocages. The conceptual framework relies on using an electron-deficient, cationic supramolecular cavity to establish CT interactions with redox-complementary, electron-rich, and water-insoluble organic guest molecules. With self-assembly playing a dominant role in guest preorganization inside cationic Pd₆L₄¹²⁺ nanocavity, we successfully demonstrated visible-light-induced O-H, N-H, and C-H bond photoactivation along with rare examples of photocatalytic C-C coupling reactions at room temperature using low-power visible-light sources. The design principles for nanocage-based catalytic cycles have relied on the strategic use of complementary donor-acceptor redox pairs, excited-state host-guest charge-transfer dynamics, confinement geometry, and the water-assisted proton-coupled electron transfer (PCET) reaction. Here, we systematically recount our conceptual framework, which emphasizes the usage of photoexcited singlet CT states in order to discover a novel bond-activation paradigm via preorganization inside water-soluble nanocages. We describe the use of broadband femtosecond transient absorption (fs-TA) spectroscopy to clock ultrafast solvation dynamics of water around the nanocage along with watching O-H, N-H, and C-H bond-breaking steps, enabled by coupling the electron transfer and proton transfer steps which are albeit temporally segregated. The significance of identifying transient absorption signatures of the photogenerated cage-confined radical species and their respective lifetimes is put in the context of driving selective oxidation reactions at sp³-, sp²-, and sp-hybridized C-H bonds; highlighting the first selective toluene-to-benzaldehyde transformation at room temperature. We further show that our methodology of host-guest CT-mediated photochemistry is general enough since it allows sp³-C-H bond functionalization inside an all-organic cationic supramolecular cavity. Finally, we delve into the necessity of modulating the confining geometry, electronics, and volume of such nanocages to completely alter product distributions, which will be a useful handle for all synthetic organic chemists.