Metal‐ and Oxidant‐Free Alkenyl C−H/Aromatic C−H Cross‐Coupling Using Electrochemically Generated Iodosulfonium Ions

A three‐step transformation consisting of 1) addition of electrochemically generated iodosulfonium ions to vinylarenes to give (1‐aryl‐2‐iodoethoxy)sulfonium ions, 2) nucleophilic substitution by subsequently added aromatic compounds to give 1,1‐diaryl‐2‐iodoethane, and 3) elimination of HI with a base to give 1,1‐diarylethenes was developed. The transformation serves as a powerful metal‐ and chemical‐oxidant‐free method for alkenyl C?H/aromatic C?H cross‐coupling.     

1,4‐Iron Migration for Expedient Allene Annulations through Iron‐Catalyzed C−H/N−H/C−O/C−H Functionalizations

C?H activation bears great potential for enabling sustainable molecular syntheses in a step‐ and atom‐economical manner, with major advances having been realized with precious 4d and 5d transition metals. In contrast, we employed earth abundant, nontoxic iron catalysts for versatile allene annulations through a unique C?H/N?H/C?O/C?H functionalization sequence. The powerful iron catalysis occurred under external‐oxidant‐free conditions even at room temperature, while detailed mechanistic studies revealed an unprecedented 1,4‐iron migration regime for facile C?H activations.     

Cobalt‐Catalyzed Oxidative C−H/C−H Cross‐Coupling between Two Heteroarenes

The first example of cobalt‐catalyzed oxidative C?H/C?H cross‐coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)₂?4 H₂O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag₂CO₃ oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C?H bond activation pathway that the well‐described oxidative C?H/C?H cross‐coupling reactions between two heteroarenes typically undergo.     

Copper‐Catalyzed Direct Sulfoximination of Heteroaromatic N‐Oxides by Dual C−H/N−H Dehydrogenative Cross‐Coupling

A dual C?H/N?H dehydrogenative coupling of quinoline‐type N‐oxides with sulfoximines that leads to N‐(hetero)arylsulfoximines in high yields has been realized by using a catalytic amount of CuBr in air. The method does not require any additional ligand, base, reactivity modifier or oxidant and provides a practical route towards a series of sulfoximidoyl‐functionalized quinolines and derivatives.     

N‐Centered Radical Directed Remote C−H Bond Functionalization via Hydrogen Atom Transfer

The N‐centered radical directed remote C?H bond functionalization via hydrogen‐atom‐transfer at distant sites has developed as an enormous potential tool for the organic synthetic chemists. Unactivated and remote secondary and tertiary, as well as selected primary C?H bonds, can be utilized for functionalization by following these methodologies. The synthesis of the heterocyclic scaffolds provides them extra attention for the modern days′ developments in this field of unactivated remote C?H bonds functionalizations.     

Mild C−H/C−C Activation by Z‐Selective Cobalt Catalysis

Cationic cobalt complexes enable unprecedented cobalt‐catalyzed C?H/C?C functionalizations with unique selectivity features. The versatile cobalt catalyst proved broadly applicable, enabled efficient C?H/C?C cleavage at room temperature, and delivered Z‐alkenes with excellent diastereocontrol.     

Ruthenium(II)‐Catalyzed Traceless C−H Functionalization Using an N−N Bond as an Internal Oxidant

A previously elusive Ru^II‐catalyzed N?N bond‐based traceless C?H functionalization strategy is reported. An N‐amino (i.e., hydrazine) group is used for the directed C?H functionalization with either an alkyne or an alkene, affording an indole derivative or olefination product. The synthesis features a broad substrate scope, superior atom and step economy, as well as mild reaction conditions.     

C−H Functionalisation for Hydrogen Isotope Exchange

The various applications of hydrogen isotopes (deuterium, D, and tritium, T) in the physical and life sciences demand a range of methods for their installation in an array of molecular architectures. In this Review, we describe recent advances in synthetic C?H functionalisation for hydrogen isotope exchange.     

Copper‐Catalyzed N−F Bond Activation for Uniform Intramolecular C−H Amination Yielding Pyrrolidines and Piperidines

The dual function of the N?F bond as an effective oxidant and subsequent nitrogen source in intramolecular aliphatic C?H functionalization reactions is explored. Copper catalysis is demonstrated to exercise full regio‐ and chemoselectivity control, which opens new synthetic avenues to nitrogenated heterocycles with predictable ring sizes. For the first time, a uniform catalysis manifold has been identified for the construction of both pyrrolidine and piperidine cores. The individual steps of this new copper oxidation catalysis were elucidated by control experiments and computational studies, clarifying the singularity of the N?F function and characterizing the catalytic cycle to be based on a copper(I/II) manifold.     

Electrochemical C−H/N−H Activation by Water‐Tolerant Cobalt Catalysis at Room Temperature

Electrochemistry enabled C?H/N?H functionalizations at room temperature by external oxidant‐free cobalt catalysis. Thus, the sustainable cobalt electrocatalysis manifold proceeds with excellent levels of chemoselectivity and positional selectivity, and with ample scope, thus allowing electrochemical C?H activation under exceedingly mild reaction conditions at room temperature in water.     

Nickel‐Catalyzed Oxidative C−H/N−H Isocyanide Insertion: An Efficient Synthesis of Iminoisoindolinone Derivatives

Transition metal‐catalyzed isocyanide insertion has served as a fundamental and important chemical transformation. Classical isocyanide insertion usually occurs between organohalides and nucleophiles, which normally involves tedious and non‐atom‐economical prefunctionalization processes. However, oxidative C?H/N?H isocyanide insertion offers an efficient and green alternative. Herein, a nickel‐catayzed oxidative C?H/N?H isocyanide insertion of aminoquinoline benzamides has been developed. Different kinds of iminoisoindolinone derivatives could be synthesized in good yields by utilizing Ni(acac)₂ as the catalyst. In this transformation, isocyanide serves as an efficient C1 connector, which further inserted into two simple nucleophiles (C?H/N?H), representing an effective way to construct heterocycles.     

Cobalt‐Catalyzed Tandem C−H Activation/C−C Cleavage/C−H Cyclization of Aromatic Amides with Alkylidenecyclopropanes

A cobalt‐catalyzed chelation‐assisted tandem C?H activation/C?C cleavage/C?H cyclization of aromatic amides with alkylidenecyclopropanes is reported. This process allows the sequential formation of two C?C bonds, which is in sharp contrast to previous reports on using rhodium catalysts for the formation of C?N bonds. Here the inexpensive catalyst system exhibits good functional‐group compatibility and relatively broad substrate scope. The desired products can be easily transformed into polycyclic lactones with m‐CPBA. Mechanistic studies revealed that the tandem reaction proceeds through a C?H cobaltation, β‐carbon elimination, and intramolecular C?H cobaltation sequence.     

Palladium‐Catalyzed C−H Alkynylation of Unactivated Alkenes

Palladium‐catalyzed regio‐ and diastereoselective C?H functionalization with bromoalkynes and electronically unbiased olefins is reported. The picolinamide directing group enables the formation of putative 5 and 6‐exo‐metallacycles as intermediates to afford monoalkynylated products in up to 91 % yield in a stereospecific fashion. The systematic study reveals that substrates with a wide range of substituents on the olefin and bromoalkyne coupling partners are tolerated. Chemoselective transformations were demonstrated for the obtained amides, olefins, and alkynes.     

Iron‐Carbonyl‐Catalyzed Redox‐Neutral [4+2] Annulation of N−H Imines and Internal Alkynes by C−H Bond Activation

Stoichiometric C?H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C?H transformations have not been developed. Herein, an iron‐catalyzed annulation of N?H imines and internal alkynes to furnish cis‐3,4‐dihydroisoquinolines is described, and represents the first iron‐carbonyl‐catalyzed C?H activation reaction of arenes. Remarkablely, this is also the first redox‐neutral [4+2] annulation of imines and alkynes proceeding by C?H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C?H bond activation to afford a dinuclear ferracycle and a synergetic diiron‐promoted H‐transfer to the alkyne as the turnover‐determining step.     

Chemically Non‐Innocent Cyclic (Alkyl)(Amino)Carbenes: Ligand Rearrangement,C−H and C−F Bond Activation

A cyclic (alkyl)(amino)carbene (CAAC) was found to undergo unprecedented rearrangements and transformations of its core structure in the presence of Group 1 and 2 metals. Although the carbene was also found to be prone to intramolecular C?H activation, it was competent for intermolecular activation of a variety of sp‐, sp²‐, and sp³‐hybridized C?H bonds. Double C?F activation of hexafluorobenzene was also observed in this work. These processes all hold relevance to the role of these carbenes in catalysis, as well as to their use in the synthesis of new and unusual main group or transition metal complexes.     

Cobalt‐Catalyzed Cyclization of N‐Methoxy Benzamides with Alkynes using an Internal Oxidant through C−H/N−O Bond Activation

The cyclization of substituted N‐methoxy benzamides with alkynes in the presence of an easily affordable cobalt complex and NaOAc provides isoquinolone derivatives in good to excellent yields. The cyclization reaction is compatible with a range of functional group‐substituted benzamides, as well as ester‐ and alcohol‐substituted alkynes. The cobalt complex [Co^IIICp*(OR)₂] (R=Me or Ac) serves as an efficient catalyst for the cyclization reaction. Later, isoquinolone derivatives were converted into 1‐chloro and 1‐bromo substituted isoquinoline derivatives in excellent yields in the presence of POCl₃ or PBr₃.     

Electrochemical Oxidative C−H/N−H Coupling between γ‐Lactams and Anilines

A mild method for the direct C?H/N?H coupling between γ‐lactams and anilines through electrochemical oxidation has been developed. The protocol proceeded smoothly without metal catalysts at room temperature to afford γ‐substituted γ‐lactams in good yields. It has been revealed that the quasi‐divided cell which provided high current density on the anode was crucial for this reaction.     

Overcoming the Limitations of C−H Activation with Strongly Coordinating N‐Heterocycles by Cobalt Catalysis

Strongly coordinating nitrogen heterocycles, including pyrimidines, oxazolines, pyrazoles, and pyridines, were fully tolerated in cobalt‐catalyzed C?H amidations by imidate assistance. Structurally complex quinazolines are thus accessible in a step‐economic manner. Our findings also establish the relative powers of directing groups in cobalt(III)‐catalyzed C?H functionalization for the first time.     

Increasing Catalyst Efficiency in C−H Activation Catalysis

C?H activation reactions with high catalyst turnover numbers are still very rare in the literature and 10 mol % is a common catalyst loading in this field. We offer a representative overview of efficient C?H activation catalysis to highlight this neglected aspect of catalysis development and inspire future effort towards more efficient C?H activation. Examples ranging from palladium catalysis, Cp*Rh^III‐ and Cp*Co^III‐catalysis, the C?H borylation and silylation to methane C?H activation are presented. In these reactions, up to tens of thousands of catalyst turnovers have been observed.     

Micellar Catalysis for Ruthenium(II)‐Catalyzed C−H Arylation: Weak‐Coordination‐Enabled C−H Activation in H2O

Chemoselective C?H arylations were accomplished through micellar catalysis by a versatile single‐component ruthenium catalyst. The strategy provided expedient access to C?H‐arylated ferrocenes with wide functional‐group tolerance and ample scope through weak chelation assistance. The sustainability of the C?H arylation was demonstrated by outstanding atom‐economy and recycling studies. Detailed computational studies provided support for a facile C?H activation through thioketone assistance.