We present here a review of the photochemical and electrochemical applications of multi-site proton-coupled electron transfer (MS-PCET) in organic synthesis. MS-PCETs are redox mechanisms in which both an electron and a proton are exchanged together, often in a concerted elementary step. As such, MS-PCET can function as a non-classical mechanism for homolytic bond activation, providing opportunities to generate synthetically useful free radical intermediates directly from a wide variety of common organic functional groups. We present an introduction to MS-PCET and a practitioner’s guide to reaction design, with an emphasis on the unique energetic and selectivity features that are characteristic of this reaction class. We then present chapters on oxidative N–H, O–H, S–H, and C–H bond homolysis methods, for the generation of the corresponding neutral radical species. Then, chapters for reductive PCET activations involving carbonyl, imine, other X=Y π-systems, and heteroarenes, where neutral ketyl, α-amino, and heteroarene-derived radicals can be generated. Finally, we present chapters on the applications of MS-PCET in asymmetric catalysis and in materials and device applications. Within each chapter, we subdivide by the functional group undergoing homolysis, and thereafter by the type of transformation being promoted. Methods published prior to the end of December 2020 are presented.

The direct, site-selective alkylation of unactivated C­(sp3)–H bonds in organic substrates is a long-standing goal in synthetic chemistry. General approaches to the activation of strong C–H bonds include radical-mediated processes involving highly reactive intermediates, such as heteroatom-centered radicals. Herein, we describe a catalytic, intermolecular C–H alkylation that circumvents such reactive species via a new elementary step for C–H cleavage involving multisite-proton-coupled electron transfer (multisite-PCET). Mechanistic studies indicate that the reaction is catalyzed by a noncovalent complex formed between an iridium­(III) photocatalyst and a monobasic phosphate base. The C–H alkylation proceeds efficiently using diverse hydrocarbons and complex molecules as the limiting reagent and represents a new approach to the catalytic functionalization of unactivated C­(sp3)–H bonds.

We report evidence of excited-state ion pair reorganisation in a cationic iridium (III) photoredox catalyst in 1,4-dioxane. Microwave-frequency dielectric-loss measurements combined with accurate calculations of dipolar relaxation time allow us to assign both ground and excited-state molecular dipole moments in solution and determine the polarizability volume in the excitedstate. These measurements show significant changes in ground-state dipole moment between [Ir[dF(CF 3 )ppy] 2 (dtbpy)]PF 6 (10.74 Debye) and [Ir[dF(CF 3 )ppy] 2 (dtbpy)]BAr F 4 (4.86 Debye). Photoexcitation of each complex results in population of highly mixed ligand centered and metal-to-ligand charge transfer states with enormous polarizability. Relaxation to the lowest lying excited-state leads to a negative change in the dipole moment for [Ir[dF(CF 3 )ppy] 2 (dtbpy)]PF 6 , and a positive change in dipole moment for [Ir[dF(CF 3 )ppy] 2 (dtbpy)]BAr F 4 . These observations are consistent with a sub-nanosecond reorganization with the PF − 6 counter-ion, which cancels the dipole moment of the lowest lying excited-state, a process which is absent for the BAr F− 4 counter-ion. Taken together, these observations suggest contact-ion pair formation between the cationic metal complex and the PF − 6 anion and, at most, solvent-separated pairing with BAr F− 4 . The dynamic ion pair reorganisation we observe with the PF − 6 counter-ion may substantially modify both the thermodynamic potential available for electron transfer and kinetically inhibit oxidative catalysis, as the anion moves to cover the positively charged end of the molecule, providing a possible mechanistic explanation for recently observed trends in the catalytic activity of these complexes as a function of anion identity in low-polarity solvents. These tunable ion-pair dynamics could prove to be a valuable tool for tailoring the reactivity of both new and extant photocatalysts.

Upon photoinitiated electron transfer, charge recombination limits the quantum yield of photoredox reactions for which the rates for the forward reaction and back electron transfer are competitive. Taking inspiration from a proton-coupled electron transfer (PCET) process in Photosystem II, a benzimidazole-phenol (BIP) has been covalently attached to the 2,2′-bipyridyl ligand of [Ir(dF(CF 3 )ppy) 2 (bpy)][PF 6 ] (dF(CF 3 )ppy = 2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine; bpy = 2,2′-bipyridyl). Excitation of the [Ir(dF(CF 3 )ppy) 2 (BIP-bpy)][PF 6 ] photocatalyst results in intramolecular PCET to form a charge-separated state with oxidized BIP. Subsequent reduction of methyl viologen dication (MV 2+ ), a substrate surrogate, by the reducing moiety of the charge separated species demonstrates that the inclusion of BIP significantly slows the charge recombination rate. The effect of ∼24-fold slower charge recombination in a photocatalytic phthalimide ester reduction resulted in a greater than 2-fold increase in reaction quantum efficiency.

Magic-sized clusters (MSCs) are kinetically stable, atomically precise intermediates along the quantum dot (QD) reaction potential energy surface. Literature precedent establishes two classes of cadmium selenide MSCs with QD-like inorganic cores: one class is proposed to be cation-rich with a zincblende crystal structure, while the other is proposed to be stoichiometric with a “wurtzite-like” core. However, the wide range of synthetic protocols used to access MSCs has made direct comparison of their structure and surface chemistry difficult. Furthermore, the physical and chemical relationship between MSC polymorphs has yet to be established. Here, we demonstrate that both cation-rich and stoichiometric CdSe MSCs can be synthesized from identical reagents and can be interconverted through the addition of either excess cadmium or selenium precursor. The structural and compositional differences between these two polymorphs can be contrasted using a combination of 1H-NMR spectroscopy, x-ray diffraction, pair distribution function (PDF) analysis, inductively coupled plasma optical emission spectroscopy, and UV-vis transient absorption spectroscopy. The subsequent polymorph interconversion reactions are monitored by UV-vis spectroscopy, with evidence for an altered cluster atomic structure observed by powder x-ray diffraction and PDF analysis. This work helps simplify the complex picture of the CdSe nanocrystal landscape and provides a method to explore structure-property relationships in colloidal semiconductors through atomically precise synthesis.