Conspectus Methods that enable the selective functionalization of C–C bonds offer unique opportunities for the skeletal diversification of complex molecules and provide access to unique structures without the need for de novo synthesis. While considerable advances have been made in transition metal-based approaches, much recent work has focused on alternative strategies for C–C bond cleavage enabled by transient free radicals. In particular, alkoxy radicals derived from simple alcohols are known to significantly destabilize adjacent C–C bonds, enabling spontaneous cleavage to eject a carbon-centered radical and afford carbonyl products via β-fragmentation. While this reactivity has long been recognized, its applications in synthesis have been limited, in part, by the challenges associated with generating the key alkoxy radical intermediates. The high bond dissociation free energies (BDFEs) of aliphatic alcohol O–H bonds (~105 kcal/mol) preclude direct homolytic activation by hydrogen atom transfer, and most established strategies rely instead on stoichiometric prefunctionalization of the O–H bond. These approaches often further limit the scope of amenable chemistries that can be applied for post-cleavage alkyl radical functionalization. Methods that could overcome these constraints have considerable synthetic potential, enabling straightforward access to reconfigured carbon frameworks from an abundant class of starting materials, as well as modular opportunities for radical functionalization. In this Account, we present our efforts towards the development of proton-coupled electron transfer (PCET) as a general mechanism for alkoxy radical generation from simple alcohols. In turn, this advance enabled us to develop a suite of novel methods for editing the frameworks of complex carbon frameworks via the cleavage and functionalization of C(sp3)–C(sp3) bonds. We first discuss the development of catalytic ring-opening isomerization reactions of cyclic benzylic carbinols to access linear aryl ketone products through a redox-relay approach. In these reactions, single electron oxidation of the substrate arene by an excited-state Ir(III) photocatalyst generates an arene radical cation that serves as an internal oxidant for an intramolecular PCET event, furnishing the alkoxy radical intermediate. This intermediate then undergoes C–C β-scission to provide the isomerized linear ketone products. We next present the discovery of an improved catalytic system for the direct activation of simple aliphatic alcohols. We then apply these chemistries for the light-driven depolymerization of lignin biopolymers, commercial phenoxy resins, hydroxylated polymers, and thiol epoxy thermosets. Notably, many of these redox isomerization reactions are thermodynamically unfavorable, providing isomerization products that are thermodynamically less stable than their corresponding starting materials. We then discuss the application of O–H PCET for the reconfiguration of saturated carbocyclic frameworks to provide expanded and contracted carbocyclic products. Applications of this reconfiguration strategy toward the 1,3-alkyl rearrangement of linear alcohols are also presented. Lastly, we discuss a method for the peripheral-to-core transposition of amine groups of saturated cyclic amino alcohols to access nitrogen-containing heterocyclic products. Taken together, these examples highlight how excited-state PCET can be leveraged for the catalytic generation of high energy O-centered radicals for regioselective C–C bond cleavage and enables the direct reconfiguration of complex carbon frameworks.
Abstract The C-H and C-C homolytic bond scissions in alkanes, alkenes and halogenated compounds, and the reverse reactions (radical self- and cross-combinations) were studied by means of the Austin model 1 (AM1) including configuration interaction (CI 3 × 3, open-shell excited singlet) in order to check on the applicability of the method for determining the energy profiles of bond scissions. The bond dissociation energies (BDEs) and the activation energies ( E A ) of the combinations were calculated. The method predicts that BDEs are better than MNDO/CI 3 × 3 for determining C-H and C-C bond scissions yielding alkyl radicals. The method is also applicable when radicals with delocalized π-electron systems are formed. The predicted EA values of the self-combinations are superior to the values obtained with MNDO/CI 3 × 3.
Metal-free radical borylation has emerged as a powerful and sustainable alternative to transition-metal-catalyzed methods, addressing challenges such as residual metal contamination, functional group sensitivity, and the high cost of precious metals. This review provides a comprehensive analysis of the mechanistic underpinnings and catalytic innovations driving this rapidly evolving field. We delve into the fundamental steps of radical generation, including homolytic B-X bond cleavage and the formation of alkyl, aryl, and boryl radicals through single-electron transfer (SET), hydrogen atom transfer (HAT), and energy transfer (EnT) pathways. Recent strategic developments are critically evaluated, including photoinduced processes such as electron donor-acceptor (EDA) complex activation, consecutive photoinduced electron transfer (ConPET), and polarity reversal catalysis and electrochemical activation using organic mediators and thermal initiation <i>via</i> radical chain processes. Unlike previous reviews, we place a special emphasis on catalytic strategies, substrate scope limitations, and emerging approaches for achieving regiocontrol. The synthetic utility of metal-free radical borylation is highlighted through its application in the late-stage functionalization of pharmaceuticals, natural products, and other complex molecules, enabling transformations that are often difficult to achieve using traditional methods. Finally, we outline the key challenges that continue to shape the field, including selective borylation of unactivated C(sp<sup>3</sup>)-H bonds and the scalability of photochemical and electrochemical systems, while also identifying promising future directions in enhancing atom economy, deepening mechanistic understanding, and integrating method development with cutting-edge technology such as high-throughput screening and machine learning. By bridging fundamental radical principles with practical synthesis, this review aims to serve as a roadmap for the continued development of metal-free boron chemistry.
In this work, the interaction of B vitamins with α-hydroxyl-containing carbon-centered radicals formed upon the irradiation of deaerated aqueous solutions of ethanol, ethylene glycol, α-methylglycoside, maltose, and α-glycerophosphate at pH 7 was studied by means of continuous radiolysis. Within the framework of the density functional theory, the homolytic bond dissociation enthalpies (BDEs) of -C-H, -O-H, and -N-H bonds and H-atom addition enthalpies (HAEs) at the -C=O and -C=N groups of the test compounds were calculated. The set of the experimental and theoretically calculated data suggests that vitamin B2, nicotinamide and pyridoxal phosphate effectively oxidize α-hydroxyl-containing carbon-centered radicals, whereas vitamins B1 and B6 reduce these radicals to prevent their recombination and fragmentation reactions.
radicals being alkynylated are formed from the cleavage of C-H bonds; standard radical precursors … Production by Photolysis Photolysis can be used to achieve homolytic fission. For example, azo compounds … Yb(OTf)3-promoted atom Et3B R1 R2 R1 H R^ECH + R2I - C=C + C=C hexane { 'H |' 'R2 25 °C R1 R2 yield (%)
cleaved homolytically, two radical species are formed that can recombine to repair damage or can initiate other homolytic cleavages which can in turn
Self-healing materials are artificial or synthetically created substances that have the built-in ability to automatically repair damages to themselves without any external diagnosis of the problem or human intervention. Generally, materials will degrade over time due to fatigue, environmental conditions, or damage incurred during operation. Cracks and other types of damage on a microscopic level h
Polymers have been observed to undergo homolytic bond cleavage through the use of radical reporters such as DPPH (2,2-diphenyl-1-picrylhydrazyl) and PMNB (pentamethylnitrosobenzene.) When a bond is cleaved homolytically, two radical species are formed that can recombine to repair damage or can initiate other homolytic cleavages which can in turn lead to more damage.
Everything we examined (6)
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