Electrophilic Aromatic Substitution with Silicon Electrophiles: Catalytic Friedel–Crafts C−H Silylation

Electrophilic aromatic substitution is a fundamental reaction in synthetic chemistry. It converts C−H bonds of sufficiently nucleophilic arenes into C−X and C−C bonds using either stoichiometrically added or catalytically generated electrophiles. These reactions proceed through Wheland complexes, cationic intermediates that rearomatize by proton release. Hence, these high‐energy intermediates are nothing but protonated arenes and as such strong Brønsted acids. The formation of protons is an issue in those rare cases where the electrophilic aromatic substitution is reversible. This situation arises in the electrophilic silylation of C−H bonds as the energy of the intermediate Wheland complex is lowered by the β‐silicon effect. As a consequence, protonation of the silylated arene is facile, and the reverse reaction usually occurs to afford the desilylated arene. Several new approaches to overcome this inherent challenge of C−H silylation by S_EAr were recently disclosed, and this Minireview summarizes this progress.     

Cobalt-Catalyzed Addition of Arylzinc Reagents to Alkynes to Form ortho-Alkenylarylzinc Species through 1,4-Cobalt Migration

Migratory carbometalation: A cobalt-Xantphos complex catalyzes the addition of an arylzinc reagent to an unactivated internal alkyne; the reaction most likely involves insertion of the alkyne into an arylcobalt species and vinyl-to-aryl 1,4-cobalt migration, followed by transmetalation with the arylzinc reagent. Interception of the resulting ortho-alkenylarylzinc species with electrophiles allows access to 1-alkenyl arenes functionalized in the 2-position.     

Pd−X Bond Homolysis Dissociation Free Energy (BDFE) Scales of [(tmeda)Pd(4-F−C6H4)X] (X=OR,NHAr) in DMSO

Transition metal intermediates bearing M−X σ-bonds are ubiquitous in metal-mediated C−X bond transformations. Thermodynamic knowledge of M−X bond cleavage is crucial to explore relevant reactions; but little was accumulated till present due to lack of suitable determination methods. We here report the first systematic study of the Pd−X bond homolysis dissociation free energies [BDFE(Pd−X)] of representative [(tmeda)Pd(4-F−C₆H₄)X] (tmeda=N,N,N′,N′-tetramethylethylenediamine, X=OR or NHAr) in DMSO on the basis of reliable measurement of their bond heterolysis energies (ΔG_het(Pd−X)). Despite ΔG_het(Pd−O)s of palladium-phenoxides are generally found about 8 kcal/mol smaller than ΔG_het(Pd−N)s of palladium-amidos, their BDFE(Pd−X)s are observed comparable. The structure-property relationship was investigated to disclose an enhancement effect of electron-withdrawing groups on BDFE(Pd−X)s. Linear free energy relationship analysis revealed that Pd−X bonds are more sensitive than X−H bonds to structural variation. The energetic propensity of reductive elimination from arylpalladium complexes was evaluated by combinatorial use of BDFE(Pd−X)s and BDFE(C−X)s, indicating an overall thermodynamic bias to C−N bond formation.     

Regio- and Stereoselective Thianthrenation of Olefins To Access Versatile Alkenyl Electrophiles

Herein, we report a regioselective alkenyl electrophile synthesis from unactivated olefins that is based on a direct and regioselective C−H thianthrenation reaction. The selectivity is proposed to arise from an unusual inverse-electron-demand hetero-Diels–Alder reaction. The alkenyl sulfonium salts can serve as electrophiles in palladium- and ruthenium-catalyzed cross-coupling reactions to make alkenyl C−C, C−Cl, C−Br, and C−SCF₃ bonds with stereoretention.     

C−X Bond Activation by Palladium: Steric Shielding versus Steric Attraction

The C−X bond activation (X = H, C) of a series of substituted C(n°)−H and C(n°)−C(m°) bonds with C(n°) and C(m°) = H₃C− (methyl, 0°), CH₃H₂C− (primary, 1°), (CH₃)₂HC− (secondary, 2°), (CH₃)₃C− (tertiary, 3°) by palladium were investigated using relativistic dispersion-corrected density functional theory at ZORA-BLYP-D3(BJ)/TZ2P. The effect of the stepwise introduction of substituents was pinpointed at the C−X bond on the bond activation process. The C(n°)−X bonds become substantially weaker going from C(0°)−X, to C(1°)−X, to C(2°)−X, to C(3°)−X because of the increasing steric repulsion between the C(n°)- and X-group. Interestingly, this often does not lead to a lower barrier for the C(n°)−X bond activation. The C−H activation barrier, for example, decreases from C(0°)−X, to C(1°)−X, to C(2°)−X and then increases again for the very crowded C(3°)−X bond. For the more congested C−C bond, in contrast, the activation barrier always increases as the degree of substitution is increased. Our activation strain and matching energy decomposition analyses reveal that these differences in C−H and C−C bond activation can be traced back to the opposing interplay between steric repulsion across the C−X bond versus that between the catalyst and substrate.     

Borazine‐CF3− Adducts for Rapid,Room Temperature,and Broad Scope Trifluoromethylation

A fluoroform‐derived borazine CF₃⁻ transfer reagent is used to effect rapid nucleophilic reactions in the absence of additives, within minutes at 25 °C. Inorganic electrophiles spanning seven groups of the periodic table can be trifluoromethylated in high yield, including transition metals used for catalytic trifluoromethylation. Organic electrophiles included (hetero)arenes, enabling C−H and C−X trifluoromethylation reactions. Mechanistic analysis supports a dissociative mechanism for CF₃⁻ transfer, and cation modification afforded a reagent with enhanced stability.     

Homolytic X-H Bond Cleavage at a Gold(III) Hydroxide: Insights into One-Electron Events at Gold

C(sp³)-H and O−H bond breaking steps in the oxidation of 1,4-cyclohexadiene and phenol by a Au(III)-OH complex were studied computationally. The analysis reveals that for both types of bonds the initial X−H cleavage step proceeds via concerted proton coupled electron transfer (cPCET), reflecting electron transfer from the substrate directly to the Au(III) centre and proton transfer to the Au-bound oxygen. This mechanistic picture is distinct from the analogous formal Cu(III)-OH complexes studied by the Tolman group (J. Am. Chem. Soc. 2019 , 141, 17236–17244), which proceed via hydrogen atom transfer (HAT) for C−H bonds and cPCET for O−H bonds. Hence, care should be taken when transferring concepts between Cu−OH and Au−OH species. Furthermore, the ability of Au−OH complexes to perform cPCET suggests further possibilities for one-electron chemistry at the Au centre, for which only limited examples exist.     

Nickel-Catalyzed Cross-Coupling of Sulfonamides With (Hetero)aryl Chlorides

The development of Ni-catalyzed C−N cross-couplings of sulfonamides with (hetero)aryl chlorides is reported. These transformations, which were previously achievable only with Pd catalysis, are enabled by use of air-stable ( L )NiCl(o-tol) pre-catalysts (L= PhPAd-DalPhos and PAd2-DalPhos ), without photocatalysis. The collective scope of (pseudo)halide electrophiles (X=Cl, Br, I, OTs, and OC(O)NEt₂) demonstrated herein is unprecedented for any reported catalyst system for sulfonamide C−N cross-coupling (Pd, Cu, Ni, or other). Preliminary competition experiments and relevant coordination chemistry studies are also presented.     

Blue-Shift Hydrogen Bonds in Silyltriptycene Derivatives: Antibonding σ* Orbitals of the Si−C Bond as Effective Acceptors of Electron Density

Triptycene derivatives are widely utilized in different fields of chemistry and materials sciences. Their physicochemical properties, often of pivotal importance for the rational design of triptycene-based functional materials, are influenced by noncovalent interactions between substituents mounted on the triptycene skeleton. Herein, a unique interaction between electron-rich substituents in the peri position and the silyl group located on the bridgehead sp³-carbon is discussed on the example of 1,4-dichloro-9-(p-methoxyphenyl)-silyltriptycene (TRPCl) which exists in solution in the form of two rotamers differing by dispositions, syn or anti, of the Si−C_Ph (the C_Ph atom is from the p-methoxyphenyl group) bond against the peri-Cl atom. For the first time, substantial differences between the Si−C_Ph bonds in these two dispositions are identified, based on indirect experimental and direct theoretical evidence. For these two orientations, the experimental ¹J(Si,C_Ph) values differ by as much as 10 percent. The differences are explained in terms of effective electron density transfer from the peri-Cl atom to the antibonding σ* orbitals of the Si−X bonds (X=H, C_Ph) oriented anti to that atom. The electronic effects are revealed by an NBO analysis. Connections of these observations with the notion of blue-shifting hydrogen bonds are discussed.     

CF3SO2Na as a Bifunctional Reagent: Electrochemical Trifluoromethylation of Alkenes Accompanied by SO2 Insertion to Access Trifluoromethylated Cyclic N-Sulfonylimines

An unprecedented electrochemical trifluoromethylation/SO₂ insertion/cyclization process has been achieved in an undivided cell in an atom-economic fashion. The protocol relies on tandem cyclization of N-cyanamide alkenes by using Langlois’ reagent as a source of both CF₃ and SO₂ under direct anodically oxidative conditions, in which two C−C bonds, two C−X bonds (N−S and S−C), and two rings were formed in a single operation. This transformation enabled efficient construction of various trifluoromethylated cyclic N-sulfonylimines from readily accessible materials.     

Spectroscopic and Crystallographic Characterization of the R3N+−C−H⋅⋅⋅X Interaction

As appreciation for nonclassical hydrogen bonds has progressively increased, so have efforts to characterize these interesting interactions. Whereas several kinds of C−H hydrogen bonds have been well-studied, much less is known about the R₃N⁺−C−H⋅⋅⋅X variety. Herein, we present crystallographic and spectroscopic evidence for the existence of these interactions, with special relevance to Selectfluor chemistry. Of particular note is the propensity for Lewis bases to engage in nonclassical hydrogen bonding over halogen bonding with the electrophilic F atom of Selectfluor. Further, the first examples of ¹H NMR experiments detailing R₃N⁺−C−H⋅⋅⋅X (X=O, N) hydrogen bonds are described.     

Iodine and Iodide in Reductive Transformations

This review provides a comprehensive overview of strategies and methodologies for reducing C−O and heteroatomic−oxygen bonds (N−O, S−O, P−O) using I₂/I⁻, as well as other synthetically relevant bonds such as C−C, N−N, C−N, C−X, C−S. It highlights and discusses most of the mechanistic details provided by the original authors. Selected examples of other halides (Br and Cl) as reductants are also covered.     

Chemoselective Coupling of π-Systems to Access Metallated 1,4- or 1,5-Skipped Dienes in Multicomponent Reactions

Integrating distinct unsaturated C−C systems while simultaneously installing metallic groups has been significantly challenging to execute in a multicomponent reaction. Therefore, designing a suitable mechanistic pathway that provides the required reactivity and selectivity for target C−C bonds with metallic reagents to ensure successful coupling is the key to success. Copper-catalyzed borylallylation and silylallylation have emerged as the most efficient strategies for assembling borylated/silylated skipped (1,4 or 1,5) dienes by catalytically combining an organocopper intermediate with allyl electrophiles. However, reactions involving interelemental reagents (e. g., [Si]−[B]) to accomplish intermolecular atom-economic couplings have not been studied thoroughly. Therefore, to aid the development of new transformations in this research area, this article attempts to include all precedents, including recent studies by the authors. The present Concept article may be helpful for researchers working in this area as it provides a basic conceptual framework.     

Light-Promoted Nickel Catalysis: Etherification of Aryl Electrophiles with Alcohols Catalyzed by a NiII-Aryl Complex

A highly effective C−O coupling reaction of (hetero)aryl electrophiles with primary and secondary alcohols is reported. Catalyzed by a Ni^II-aryl complex under long-wave UV (390–395 nm) irradiation in the presence of a soluble amine base without any additional photosensitizer, the reaction enables the etherification of aryl bromides and aryl chlorides as well as sulfonates with a wide range of primary and secondary aliphatic alcohols, affording synthetically important ethers. Intramolecular C−O coupling is also possible. The reaction appears to proceed via a Ni^I–Ni^III catalytic cycle.     

Neutral and Anionic Diboron Compounds Bearing Electron-Precise B−B Bond

Electron-precise B−B bonded compounds are valuable reagents in organic syntheses, which can be used as key starting material for the synthesis of functionalized organoboranes. Bis(pinacolato)diborane(4) B₂pin₂ and its derivatives are among the most studied diboron species. However, their B−B bonds usually need to be activated by transition metal catalysts or bases for further transformations. Recently, many well-designed/reactive electron-precise B−B bonded compounds have been developed, which could facilitate direct reactions with small molecules, unsaturated substrates, and electrophiles. This review highlights the synthesis, structure, and reactivity of neutral and anionic B−B bonded compounds.     

Electroreductive Cross-Electrophile Coupling (eXEC) Reactions

Electrochemistry utilizes electrons as a potent, controllable, and traceless alternative to chemical oxidants or reductants, and typically offers a more sustainable option for achieving selective organic synthesis. Recently, the merger of electrochemistry with readily available electrophiles has been recognized as a viable and increasingly popular methodology for efficiently constructing challenging C−C and C-heteroatom bonds in a sustainable manner for complex organic molecules. In this mini-review, we have systematically summarized the most recent advances in electroreductive cross-electrophile coupling (eXEC) reactions during the last decade. Our focus has been on readily available electrophiles, including aryl and alkyl organic (pseudo)halides, as well as small molecules such as CO₂, SO₂, and D₂O.     

Ni(II) Precatalysts Enable Thioetherification of (Hetero)Aryl Halides and Tosylates and Tandem C−S/C−N Couplings

Ni-catalyzed C−S cross-coupling reactions have received less attention compared with other C-heteroatom couplings. Most reported examples comprise the thioetherification of most reactive aryl iodides with aromatic thiols. The use of C−O electrophiles in this context is almost uncharted. Here, we describe that preformed Ni(II) precatalysts of the type NiCl(allyl)(PMe₂Ar’) (Ar’=terphenyl group) efficiently couple a wide range of (hetero)aryl halides, including challenging aryl chlorides, with a variety of aromatic and aliphatic thiols. Aryl and alkenyl tosylates are also well tolerated, demonstrating, for the first time, to be competent electrophilic partners in Ni-catalyzed C−S bond formation. The chemoselective functionalization of the C−I bond in the presence of a C−Cl bond allows for designing site-selective tandem C−S/C−N couplings. The formation of the two C-heteroatom bonds takes place in a single operation and represents a rare example of dual electrophile/nucleophile chemoselective process.     

Iridium(III)-Catalyzed Intermolecular C(sp3)−H Insertion Reaction of Quinoid Carbene: A Radical Mechanism

Described herein is an Ir^III/porphyrin-catalyzed intermolecular C(sp³)−H insertion reaction of a quinoid carbene (QC). The reaction was designed by harnessing the hydrogen-atom transfer (HAT) reactivity of a metal-QC species with aliphatic substrates followed by a radical rebound process to afford C−H arylation products. This methodology is efficient for the arylation of activated hydrocarbons such as 1,4-cyclohexadienes (down to 40 min reaction time, up to 99 % yield, up to 1.0 g scale). It features unique regioselectivity, which is mainly governed by steric effects, as the insertion into primary C−H bonds is favored over secondary and/or tertiary C−H bonds in the substituted cyclohexene substrates. Mechanistic studies revealed a radical mechanism for the reaction.     

A Robust and Broadly Applicable Cobalt‐Catalyzed Cross‐Coupling of Functionalized Bench‐Stable Organozinc Pivalates with Unsaturated Halides

We report a robust and broadly applicable CoCl₂‐catalyzed cross‐coupling between functionalized aryl and heteroaryl zinc pivalates and various electron‐poor aryl and heteroaryl halides (X=Cl, Br, I). Couplings with (E)‐ or (Z)‐bromo‐ or iodo‐alkenes proceed with retention of configuration. Also, alkynyl bromides react with arylzinc pivalates providing arylated alkynes.