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1. Catalysis & inhibition issues associated with Monoamine Oxidase (MAO). How unusually low α-C-H bond dissociation energies may open the door to single electron transfer

   https://doi.org/10.1016/j.ctta.2023.100119  

   González, Jonathan Sánchez; Tanko, JM (December 2023, Chemical Thermodynamics and Thermal Analysis)

   C-H Bond dissociation energies for a unique selection of tertiary amines that are known substrates or inhibitors of monoamine oxidase have been calculated using density functional theory. These amines are unusual because they are the only tertiary amines that exhibit MAO substrate or inhibitor behavior. The unique structural feature common to these specific compounds is an sp3-hybridized CH2 moiety, which is -both to nitrogen and an C=C or C≡C. The stabilization afforded the resulting radicals by extended delocalization dramatically lowers both the C-H bond strength of the substrate (R-H → R• + H•) and pKa of the corresponding radical cation (RH•+ → R• + H+). This interplay of structure and thermodynamics may provide the driving force for an electron transfer mechanism for MAO catalysis and inhibition. 

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2. Reaction of O ₂ with α-Aminoalkyl Radicals Derived from Tetrahydropyridines

   https://doi.org/10.1021/acs.jpca.5c02967  

   Venturo, Paul; Castagnoli, Neal; Tanko, James M (June 2025, The Journal of Physical Chemistry A)

   Tetrahydropyridines, such as the Parkinsonian-symptom-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its derivatives are unique in that they are the only known tertiary amines that are monoamine oxidase (MAO) substrates or inhibitors. These compounds all possess an exceptionally weak C-H bond at C-6, which is alpha both to a nitrogen lone pair and a C=C. Radicals (R•) derived from hydrogen abstraction at this position are exceptionally stable. Similar to other -aminoalkyl radicals, these radicals react with oxygen at a nearly diffusion-controlled rate and are readily oxidized. Evidence suggests that while the initial product of this reaction is likely a peroxyl radical resulting from radical trapping (ROO•), a dihydropyridinium species (DHP+) is produced through what can be described as an overall inner-sphere electron transfer process. These results imply another role for O2 in the MAO catalytic cycle. In addition to regenerating the flavin moiety in MAO, O2 may also be directly involved in oxidizing the substrate radical. 

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3. A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor

   https://doi.org/10.1038/s41467-021-27165-z  

   Leibler, Isabelle Nathalie-Marie; Tekle-Smith, Makeda A.; Doyle, Abigail G. (December 2021, Nature Communications)

   Abstract Photoredox catalysis has provided many approaches to C(sp 3 )–H functionalization that enable selective oxidation and C(sp 3 )–C bond formation via the intermediacy of a carbon-centered radical. While highly enabling, functionalization of the carbon-centered radical is largely mediated by electrophilic reagents. Notably, nucleophilic reagents represent an abundant and practical reagent class, motivating the interest in developing a general C(sp 3 )–H functionalization strategy with nucleophiles. Here we describe a strategy that transforms C(sp 3 )–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. The resulting carbocation is functionalized by a variety of nucleophiles—including halides, water, alcohols, thiols, an electron-rich arene, and an azide—to effect diverse bond formations. Mechanistic studies indicate that HAT is mediated by methyl radical—a previously unexplored HAT agent with differing polarity to many of those used in photoredox catalysis—enabling new site-selectivity for late-stage C(sp 3 )–H functionalization. 

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4. The Role of Electron Transfer in Copper‐Mediated C(sp ² )−H Trifluoromethylation

   https://doi.org/10.1002/anie.202420677  

   Ball, Margaret_A P; Myers, Preston J; Ritch, Grayson D; Bower, Jamey K; Moore, Curtis E; Szymczak, Nathaniel K; Zhang, Shiyu (February 2025, Angewandte Chemie International Edition)

   Abstract We report copper(II) and copper(III) trifluoromethyl complexes supported by a pyridinedicarboxamide ligand (L) as a platform for investigating the role of electron transfer in C(sp²)−H trifluoromethylation. While the copper(II) trifluoromethyl complex is unreactive towards (hetero)arenes, the formal copper(III) trifluoromethyl complex performs C(sp²)−H trifluoromethylation of a wide range of (hetero)arenes. Mechanistic studies using the copper(III) trifluoromethyl complex suggest that the mechanism of arene trifluoromethylation is substrate‐dependent. When the thermodynamic driving force for electron transfer is high, the reaction proceeds through a previously unidentified single electron transfer (SET) mechanism, where an initial electron transfer occurs between the substrate and oxidant prior to CF₃group transfer. Otherwise, a CF₃radical release/electrophilic aromatic substitution (S_EAr) mechanism is followed. These studies provide valuable insights into the role of strong oxidants and potential mechanistic dichotomy in Cu‐mediated C(sp²)−H trifluoromethylation. 

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5. Group I Alkoxides and Amylates as Highly Efficient Silicon–Nitrogen Heterodehydrocoupling Precatalysts for the Synthesis of Aminosilanes

   https://doi.org/10.1002/chem.202302618  

   Reuter, Matthew B; Javier‐Jiménez, Diego R; Bushey, Claire E; Waterman, Rory (November 2023, Chemistry – A European Journal)

   Abstract Group I alkoxides are highly active precatalysts in the heterodehydrocoupling of silanes and amines to afford aminosilane products. The broadly soluble and commercially available KO^tAmyl was utilized as the benchmark precatalyst for this transformation. Challenging substrates such as anilines were found to readily couple primary, secondary, and tertiary silanes in high conversions (>90 %) after only 2 h at 40 °C. Traditionally challenging silanes such as Ph₃SiH were also easily coupled to simple primary and secondary amines under mild conditions, with reactivity that rivals many rare earth and transition‐metal catalysts for this transformation. Preliminary evidence suggests the formation of hypercoordinated intermediates, but radicals were detected under catalytic conditions, indicating a mechanism that is rare for Si−N bond formation. 

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