The possibility of direct introduction of a new functionality (or a new C–C bond) via direct C–H bond transformation is a highly attractive strategy in covalent synthesis. The range of substrates is virtually unlimited, including hydrocarbons, complex organic compounds of small molecular weight, and synthetic and biological polymers. Below is a list of recent articles on this topic. For a review, see
Activating methane: Free-energy activation and functionalization barriers were calculated for a series of rhodium(III) bis(quinolinyl)benzene (bisqx) complexes for partial oxidation of methane. An η2-benzene coordination mode encourages methyl group functionalization by serving as an effective leaving group for SN2 and SR2 attack.
Superoxoman: The title reaction was investigated and the calculations reveal that Mn–O2.− and Fe–O2.− are stronger oxidants compared to either Cr–O2.− or Cu–O2.−, and the oxidative abilities are found to be correlated to the magnetic exchange parameter J. These findings have direct relevance to the functions of several metalloenzymes.
The devil is in the detail: Linear correlation between Gibbs free energies of activation ΔG≠ and C-H bond dissociation energies DC−H for hydrocarbon oxidation by a FeVO–TAML complex falsely dictates a common mechanism for all substrates. Dissecting ΔG≠ into ΔH≠ and ΔS≠, and plotting ΔH≠ vs. DC−H reveals an alternate oxidation mechanism for the hydrocarbon with lowest DC−H.
An efficient iron-catalyzed C–H bond functionalization that proceeded through an intramolecular C–H amination reaction under nitrogen was employed for the synthesis of pyrido[1,2-a]indoles from 2-benzhydrylpyridines. Under oxygen, the same 2-benzhydrylpyridines were used for the synthesis of the corresponding tertiary alcohols. Overall, a change of atmosphere altered the course of the reaction.
As directed: The title reactions were accomplished with in situ generated cobalt(III) carboxylate complexes for highly efficient C-H activations. The direct cyanation proved viable with removable directing groups and displayed a broad substrate scope and mild reaction conditions.
The direct arylation of benzo-fused heterocycles is reported. A common strategy could be applied to benzofuran, benzothiophene, and indole with good selectivity for arylation at the 2-position. In addition, the same method could be applied to the arylation at C3 in a second C–H activation step.
A copper/silver-mediated oxidative ortho-ethynylation of unactivated aryl C-H bonds with terminal alkyne has been developed using a removable bidentate directing group (PIP; see scheme) derived from 2-(pyridine-2-yl)isopropylamine. The reaction provides an efficient synthesis of aryl alkynes with broad substrate scope, high functional-group tolerance, and compatibility with a wide range of heterocycles.
Metal-free α-arylation of ketones: A regioselective synthesis of symmetrical and unsymmetrical benzopinacolones through a metal-free aerobic dehydrogenative α-arylation at the tertiary sp3 C-H bond of substituted 1,1-diphenylketones with aromatic and heteroaromatic compounds, in the presence of K2S2O8 in CF3COOH at room temperature, is described. In addition, benzopinacolones were converted into sterically hindered, tetrasubstituted alkenes and polycyclic aromatic compounds (see scheme; DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone).
Alcohols in action: A wide range of alcohols and benzamide substrates functionalized with electron-rich or electron-poor substituents are tolerated in the title reaction. This practical reaction occurs under mild conditions.
A new efficient method for the direct alkenylation of 3-arylsydnones by palladium-catalyzed C–H functionalization is developed. The reaction proceeds smoothly at room temperature and delivers the products in yields up to 83 %.
Nickeled and dimed: Nickel(0)-catalyzed C-H functionalization of 2-pyridones and subsequent ligand-controlled regioselective cyclization affords 1,6-annulated 2-pyridones. Cyclooctadiene (L1) selectively leads to exo cyclization, whereas the addition of a bulky N-heterocyclic carbene ligand (L2) switches to the endo mode. The method was applied in the synthesis of the lupin alkaloid (±)-cytisine. LA=Lewis acid.
Platinum plays favorites: PtII complexes containing unsymmetrical (pyridyl)pyrrolide ligands are shown to catalyze the hydroarylation of unactivated alkenes with selectivity for the anti-Markovnikov product (see scheme). Substitution on the pyrrolide portion of the ligand allows effective tuning of the selectivity to anti-Markovnikov alkylarene products, whereas substitution on the pyridyl portion can promote competitive alkenylarene production.
What a pair: A RhIII/CuII-promoted process is reported to provide tetrasubstituted enol esters in a trans-selective fashion. This three-component reaction uses a rhodium(III) catalyst for the C2-selective activation of electron-rich heteroarenes and the addition across the alkyne. Copper(II) then takes over to forge the vinyl ester bond. The method was also used for the functionalization of bioactive furocoumarin natural products.
Efficient approach: An efficient rhodium(III)-catalyzed tandem three-component reaction of imines, alkynes, and aldehydes through C-H activation has been developed (see scheme). High stereo- and regioselectivity, as well as good yields were obtained in most cases. The simple and atom-economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.
Application of a unique, thermally stable, and air-stable Pd0 catalyst for the direct arylation of heteroarenes is described. The combination of only 0.5–2 mol-% of the Pd0 complex possessing an electron-deficient fluorinated phosphine ligand with a substoichiometric quantity of pivalic acid (PivOH) generates an efficient system to promote the C–H activation of a broad range of heteroarenes.
A RhIII-catalyzed procedure for the C7-selective C-H alkylation of indolines with α-diazo compounds at room temperature is reported. An IrIII-catalyzed intermolecular insertion of arene C-H bonds into α-diazo compounds has also been successfully developed (see scheme; EWG=electron-withdrawing group).
Photolysis of [Cp*Re(CO)3] with bromo- or chlorobenzene in benzene results in the formation of biphenyl and the corresponding rhenium hydride halide complex trans-[Cp*Re(CO)2H(X)]. Isotopic labeling experiments indicate that one phenyl ring in the resulting biphenyl comes from the aryl halide and the other one from the solvent benzene. Plausible mechanisms are proposed that involve intermolecular C–X and C–H activation.
An efficient RhIII-catalyzed ortho-C–H bond activation for the synthesis of substituted isoquinolines and heterocycle-fused pyridines in aqueous medium has been developed. This method involves the in situ generation of ketimines from ketones and ammonium acetate and subsequent oxidative C–H bond activation/annulation of the ketimines with alkynes to form the C–C/C–N bonds spontaneously.
The ruthenium-catalyzed alkenylation of arenes with unsaturated alkanes has been achieved by triazole-directed C–H activation. Dialkenylated arenes were efficiently produced by this method from internal alkynes as the sole products with high regio- and stereoselectivity.
A new bis(pyrazolecarboxylate) ligand undergoes C–H bond activation in the presence of Cu(ClO4)2 under mild basic conditions. The resulting coordination polymers exhibit interesting structural features with promising catalytic and magnetic properties.
All about atmosphere: A step-economical synthesis of 2-arylcyclopropylamines through the title sequence has been developed. The iridium-catalyzed C-H borylation proceeds with cis selectivity, and the subsequent Suzuki–Miyaura coupling proceeds with retention of configuration at the carbon center bearing the Bpin group, and epimerization at the nitrogen-bound carbon atoms. Either isomer (cis or trans) can be accessed by simply changing the atmosphere (N2 or O2).
The introduction of structural diversity into RhII–RhII complexes is achieved with amide-functionalized 1,8-naphthyridine ligands modulated by steric crowding, bridging carboxylate groups that are labile, and hydrogen-bonding interactions between the amide hydrogen and carboxylate oxygen atoms. The amide functionality shows hemilabile behavior at the axial sites, thus making the dirhodium complex effective for the catalytic C-H functionalization of indoles with appropriate diazo compounds (see scheme).
Light weights: The readily available nondoped GaN material possesses superior thermal stability and catalytic activity towards the non-oxidative aromatization of light alkanes (from C1 to C6) at elevated temperature. Theoretical calculations propose an energetically favorable adsorption interaction between methane and the m-plane of GaN.
Paired off: The title reaction has been achieved with cobalt-based catalytic systems featuring bis(2,4-dimethoxyphenyl)(phenyl)phosphine (L) and either 2-methoxypyridine or DBU (LB), thus affording a variety of 1,2-diarylethanes in good yields. Ligand screening and deuterium-labeling studies show the ligand and Lewis base to be important in the crucial C-C reductive elimination step. Cy=cyclohexyl, PMP=para-methoxyphenyl.
Pd makes it rotate: A C-H activation/dynamic kinetic resolution protocol is developed to access axially chiral biaryls. The isomerization step is believed to occur via a palladacyclic intermediate. Chiral induction is achieved using the sulfoxide motif as both “traceless” directing group and chiral source.
A one-pot four-step procedure was developed for the synthesis of all eight L-glycopyranosyl donors from the corresponding 6-deoxy thioglycosides. Ir-catalyzed silylation (a) and C-H activation (b), followed by a Fleming–Tamao oxidation (c) and acetylation (d) led to highly functionalized thioglycosides.
A radical way: The title reaction has been realized for many unactivated alkyl halides and a variety of heteroarenes (see picture; red dots denote the point of alkylation with secondary and tertiary alkyl halides). Preliminary mechanistic studies indicate that the palladium catalyst initiates an alkyl radical addition to heterocycles.
Double activation: The combined use of Pd(OAc)2, Cu(OAc)2, and dioxygen in molten tetrabutylammonium acetate (TBAA) promotes an unusual cyclopropanation reaction between aryl methyl ketones and styrenes. The process is a dehydrogenative cyclizing coupling that involves a twofold C-H activation at the α-position of the ketone.
Proton pincer ping-pong: New phosphine-free Ru–NCN pincer complexes have been synthesized. The complexes’ dearomatized alkoxide/hydroxide analogues undergo unprecedented regioselective, intramolecular C-H/O-H bond activation with tert-butanol or water at 25 °C, as shown by NMR spectroscopy and DFT calculations.
By no means π in the sky! The activation of aromatic C-H bonds by a transition metal catalyst has received significant attention in the synthetic chemistry community. In recent years, rapid and site-selective extension of π-electron systems by C–H activation has emerged as an ideal methodology for preparing conjugated organic materials. This Review focuses on recently developments in this area directed toward new optoelectronic materials.
Intramolecular HAT scope: The investigation of the less commonly encountered 1,n-hydrogen-atom transfer (HAT) reactions in which n≠5 has led to high yielding original synthetic applications. The aim of this Review is to make a critical updated inventory, highlighting the most elegant cascade reactions based on a 1,n-HAT elementary step (from A to B) in which n=4, 6, 7, 8, 9, and so forth.
Give me five: A regioselective C-H imidation of five-membered heterocyclic pyrrole, furan, and thiophene derivatives was realized. Through a metal catalytic or organocatalytic approach, a series of 2-amino- and β-amino-substituted heterocyclic compounds was obtained under atmospheric conditions.
The nickel-catalyzed direct decarboxylative arylation of hetereoarenes with benzoic acids through an sp2 C–H functionalization process is reported. This transformation provides the first examples of decarboxylative cross-coupling reactions with aromatic acids through nickel catalysis. IPr = 1,3-Bis(2,6-diisopropylphenyl)-imidazol-2-ylidene, BQ = 1,4-benzoquinone.
Caught in a trap: The title reaction of N,N-disubstituted anilines with diazo compounds and imines is reported for the efficient construction of α,α-diaryl benzylic quaternary stereocenters in good yields with high diastereoselectivities and excellent enantioselectivities. Efficient electrophilic trapping of the metal-carbene-induced zwitterionic intermediate is crucial for the enantiocontrol under RhII/chiral phosphoric acid (PPA) co-catalysis.
Selective C(sp2)-H activation of pyridylimidazolium or pyridyltriazolium salts affords isostructural iridium(III) complexes containing a mesoionic C-donor ligand. Despite the similar mesoionic character, the behavior of the ligands (e.g., in H/D isotope-exchange reactions) and of the complexes (in oxidation catalysis) is distinctly different (see scheme).
The three C's: An efficient rhodium(III)-catalyzed synthesis of 2H-chromenes from N-phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three-carbon unit in rhodium(III)-catalyzed C(sp2)-H activations. Preliminary mechanistic investigations are discussed.
An axe to grind? Novel axially chiral biaryls were synthesized by the direct C-H bond olefination of biaryl compounds, using a chiral [Cp*RhIII] catalyst (1), in good to excellent yields and enantioselectivities. The biaryls were found as suitable ligands for rhodium-catalyzed asymmetric conjugate addition reactions.
Modern biocatalysts on the rise: The P450 BM3 monooxygenase mutant A74G/L188Q catalyzes the enantioselective allylic hydroxylation of ω-alkenoic acids and esters under mild conditions using O2 as an oxidant. This reaction offers access to important chiral building blocks for the synthesis of biologically active compounds and demonstrates the highest chemo- and enantioselectivity observed to date for the C-H oxidation of acyclic terminal olefins.
Rhodium-catalyzed hydroarylations of heterobicyclic alkenes with NH-sulfoximines lead to products that can then be converted to aryl-fused thiazines. The initial process involves a C-H functionalization directed by the sulfoximidoyl group. Aryl addition to the alkene is then followed by dehydration and palladium-catalyzed oxidative C-N coupling (see scheme).
Radical or ionic mechanism? Both. The detailed mechanism of a silver-mediated furan formation by oxidative C-H/C-H activation has been revealed by DFT calculations and additional experiments. The reaction path starts with a radical C-C coupling process. Then, an aromatic cyclization occurs featuring an ionic mechanism, which completes the furan formation. Silver plays crucial roles in the reaction: it is an oxidant and a catalyst simultaneously.
Calculated barriers to C-H activation: The key 1,4-Rh shift step in the multiple, “merry-go-round” addition of norbornene to phenylboronic acid is shown to proceed by C-H oxidation addition (OA)/C-H reductive elimination (RE) to/from RhIII-hydride by DFT calculations (PCM/PBE0/DGDZVP level of theory). The calculated barriers are in excellent agreement with the experimental selectivity.
Overcoming inactivity: Bulky, chiral, monodentate N-heterocyclic carbene (NHC) ligands were successfully applied to the palladium-catalyzed, highly enantioselective CAr-Calkyl coupling of an unactivated C(sp3)-H bond (see scheme). Readily synthesized carbamates, containing a stereogenic center, were investigated and afforded different trans-2,3-substituted indolines. Furthermore, a DFT study was carried out to rationalize experimentally observed regio- and enantioselectivities.
Two metals are better than one: Pd/Cu-catalyzed decarboxylative/direct C-H alkenylation of heteroarenes with α-fluoroacrylic acids is reported. This method offers step-economical and stereocontrolled access to valuable heteroarylated monofluoroalkenes as both Z and E isomers.
Versatile oxidative alkenylations of sulfonic acids, sulfonyl chlorides or sulfonamides were achieved by a robust ruthenium(II) catalyst with excellent substrate scope. Mechanistic studies suggested a reversible, acetate-assisted C-H ruthenation, along with a subsequent olefin insertion.
No propane, no gain: The mechanism for the functionalization of propane with palladium(NHC) catalysts was investigated in detail. The combined experimental and computational (DFT) results favor a mechanism with CH activation by palladium(II) and oxidation by bromine to palladium(IV). It is proposed that the oxidation of palladium(II) to palladium(IV) alkyl species proceeds faster for iso-alkyl than for n-alkyl complexes.
Go with the combo: The title reaction is realized by combining asymmetric counteranion catalysis and palladium-catalyzed allylic C-H activation. This method tolerates a wide scope of α-branched aromatic aldehydes and terminal alkenes, thus affording allylation products in high yields and with good to excellent levels of enantioselectivity.
A handle on [O]: A variety of C-H oxidation methods were explored on the betulin skeleton to improve the solubility of this bioactive, yet poorly water-soluble, natural product. The innate reactivity of the molecule, as well as the molecular handles present on the core, allowed oxidations at different positions. Solubility enhancement was observed for many of the synthesized compounds.
Selective iridium: The first β-selective Ir-catalyzed C-H activation and hydrogen-isotope-exchange process by using active IrI catalyst was established. Under practically accessible reaction conditions and by employing low levels of catalyst loading, very good levels of deuterium incorporation have been obtained with appreciable selectivity over the potentially competing reduction process across a series of α,β-unsaturated substrates (see scheme).
A RhIII-catalysed ortho C–H amination of phenidones under mild conditions at room temperature was developed using N-alkyl-O-benzoyl-hydroxylamines as aminating agents, and with a cyclic hydrazine moiety as a directing group, yields of up to 97 % and a high functional group tolerance were observed.
The unique performance of MoCl5 gives rise to a variety of complex structures involving the thiophene motif. The oxidative coupling is performed in the 2,3-positions of the thiophene moiety. In this approach, the first cross-coupling reactions by using MoCl5 are established.
A copper-catalyzed asymmetric addition to isatins to give 3-hydroxy-2-oxindoles by C–H activation with a fluorous bis(oxazoline) as ligand is presented. The fluorous ligand can be easily recovered and reused at least three times without significant loss in its activity.
Minor adjustments: Two approaches are presented to functionalize the popular N1,N2-dimethyl-N1,N2-bis(pyridin-2-ylmethyl)ethane-1,2-diamine (BPMEN) ligand, so that it can be supported on porous silica or polymer resin supports. Iron that complexes with this ligand can be used in an array of catalytic C-H functionalization reactions (see picture).
Functionalization of the C(sp3)–H bonds in azaarenes catalyzed by CoCl2 as an inexpensive Lewis acid catalyst is reported. Enones are demonstrated to be good C=C electrophilic acceptors for the construction of various azaarene-containing 1,4-addition products in yields up to 95 %.
For your C-H bond only: [Rh(μ-Cl)(H)2(IPr)]2 (IPr=1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene) catalyzes the selective functionalization of 2-(2-thienyl)pyridine efficiently with a range of alkenes and internal alkynes. A catalytic cycle is proposed on the basis of the identification of key reaction intermediates and the study of their reactivity by NMR spectroscopy.
En route: The title redox-neutral reaction provides a convenient route to valuable enantioenriched trifluoromethylated N,O-aminals in good to excellent yields and with excellent regio-, chemo-, and enantioselectivity. The reaction features a CuI/Brønsted acid system and broad substrate scope.
No group help needed: A palladium-catalyzed dehydrogenative coupling between diarylamines and olefins has been discovered for the synthesis of substituted indoles. This intermolecular annulation approach incorporates readily available olefins and obviates the need for any additional directing group. An ortho palladation, olefin coordination, and β-migratory insertion sequence has been proposed for the generation of an olefinated intermediate.
Electrochemical reactions are shown to be effective for the C-H functionalization of a number of heterocyclic substrates that are recalcitrant to conventional peroxide radical initiation conditions and of interest in medicinal chemistry. Monitoring reaction progress under electrochemical conditions provides mechanistic insight into the C-H functionalization process.
Five-atom building unit: N-aryl-substituted nitrones were employed as five-atom coupling partners in the rhodium-catalyzed cyclization with diynes. In this reaction, the nitrone moiety served as a directing group for the catalytic C-H activation of the N-aryl ring. This formal [2+2+5] approach allows rapid access to bridged eight-membered heterocycles with broad substrate scope.
Branching off: The title reaction of unactivated β-methylene C(sp3)-H bonds of α-amino acid substrates with alkyl iodides is described. The C(alkyl)–C(alkyl) bond-forming reaction proceeds in good yields, and β-branched amino acids can be obtained by using sequential reactions.
Carbonylative C-H activation: A procedure for the synthesis of highly substituted 2-quinolinones has been developed. By this newly developed approach, 2-quinolinone derivatives were prepared in moderate to good yields by carbonylative [3+2+1] annulation of N-aryl-pyridine-2-amines and internal alkynes by C-H activation (see scheme).
A convenient route to phthalimide: A convergent method for the ruthenium(II)-catalyzed imidation of easily accessible benzamides by C-H functionalization was developed (see scheme). The methodology was successfully applied to the preparation of synthetically challenging unsymmetrical heteroaromatic diamides and proved amenable to a step-economic synthesis of a potent COX-2 enzyme inhibitor.
Very neat reactions! A new strategy for the synthesis of benzo[c]chromenes and benzo[b]furans from commercially available starting materials is reported. This two-step, one-pot strategy consists in a gold-catalyzed hydrophenoxylation reaction followed by Pd-catalyzed C-H activation or Mizoroki–Heck reactions.
Good form: Indolines are important moieties present in various biologically significant molecules. Described is the title sequence for forming indolines with di-tert-butyldiaziridinone. The reaction process likely proceeds via a pallada(II)cycle, which is converted into an indoline by oxidative addition to the diaziridinone and two subsequent C-N bond formations.
The weakest link: Challenging aryl C-H oxygenations with very weakly coordinating aldehydes proceed chemoselectively in the presence of versatile ruthenium(II) catalysts under mild reaction conditions. This transformation features an ample substrate scope and excellent positional selectivity.
Things go better without coke! The selective activation of methane and its direct conversion into light olefins and aromatic compounds remains a formidable challenge. Recent work shows that a catalyst material consisting of lattice-confined single iron atoms is very active and selective in the direct, nonoxidative conversion of methane into ethylene, benzene, and naphthalene without the formation of coke deposits.
Thinking outside the BBOX: γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate (2OG) dependent oxygenase that catalyzes the final hydroxylation step in the biosynthesis of carnitine. BBOX was shown to catalyze the oxidative desymmetrization of achiral N,N-dialkyl-piperidine-4-carboxylates to give products with two or three stereogenic centers.
Which C-H bond reacts? N-Ylide complexes of Ir were generated by α-C(sp3)-H activation with [Cp*IrCl2]2 and NaOAc. The reaction of an α-imidazolium ester is a rare example of a C-H activation where the site selectivity can be controlled by the choice of metal and ligand; DFT calculations revealed that the N-ylide complex is the kinetic product of an ambiphilic C-H activation, in which the acetate ligand plays the dominant role (see scheme; Cp*=pentamethylcyclopentadiene).
Metal-free direct arylations of engineered indole-3-acetamides set the stage for the late-stage diversifications of highly functionalized peptides under mild reaction conditions.
Actin' out: Spiroacetals can be prepared from aldehydes and functionalized dienes through a convergent, telescoped sequence of cycloaddition, oxidative C-H bond cleavage, and acid treatment. The functional-group tolerance and facile accessibility of the components render this procedure suitable for the synthesis of structurally complex natural products such as the actin-binding cytotoxin bistramide A.
The synthesis of a key intermediate chiral β-hydroxy-γ-butyrolactone (A) by PdII-catalysed stereoselective allylic C–H oxidation is reported. A common synthetic route to transform this intermediate into key building blocks for the synthesis of migrastatin family members has been developed.
The synthesis of indole-derived structural analogs of natural antimitotic agent allocolchicine is reported. In a key step, an intramolecular Pd-catalyzed C–H arylation reaction serves to construct the polycyclic ring system, by connecting the two electron-rich arene fragments.
Reaction of donor-stabilized silylene 1 with 1,2-dicarba-closo-dodecaborane leads to the formation of neutral six-coordinate silicon(IV) complex 2 (selective C–H bond activation). Compound 2 reacts with acetonitrile to form neutral six-coordinate silicon(IV) complex 3 and 1,2-dicarba-closo-dodecaborane.
Construction of 9-arylacridines was achieved through a new copper-mediated dehydrogenative cyclization of tritylamines involving two C-H and one C-N bond cleavages. Some of the obtained acridine derivatives exhibited intense fluorescence in the solid state (see scheme).
The coordination of alkanes to metal centers is a complex matter! Advances in synthetic strategies to produce alkane σ-complexes, and ever more detailed analyses of such complexes, is leading to an understanding of how alkanes bind to specific metal centers. Such analysis is vital in understanding selectivity in C-H activation reactions.
Much milder and environmentally friendly reaction conditions can be used for oxidative Heck reactions through the combined use of rhodium and redox catalysis. This allows the rhodium complex to be catalytically regenerated. A broad range of substrates was tolerated in the reaction and afforded different amides in good to very good yields.
Novel tool set: New methodologies for the functionalization of remote C-H bonds have been developed recently. In diverse approaches high selectivities are achieved for the functionalization of less reactive C(sp2)-H as well as C(sp3)-H bonds distal to any substituents.
This review outlines some selected examples and present challenges relating to palladium-catalyzed direct allylic functionalization. This old reaction, ignored for many years, is enjoying a new age.
When palladium meets a support: The functionalization of the C-H bond is the most straightforward approach to create new bonds. Although most studies involve homogeneous transition-metal catalysts, in this Minireview we aim to give a picture of recent advances of direct C-H arylations enabled by heterogeneous Pd catalysts.
Ligands at the wheel: The pivotal role of ligands for the palladium-catalyzed functionalization of remote C sp3-H bonds has been demonstrated. The presence of the ligand enhances the reactivity of the inert C sp3-H bond and controls the selectivity of the process. DG=Directing group, FG=functional group.
The latest developments in the field of imidazo[1,2-a]pyridine functionalization by means of cross-coupling reactions such as the Sonogashira, Heck, Negishi, Suzuki–Miyaura, and Stille reactions, as well as by C-arylation, C-alkenylation, carbonylation, and double functionalization, are reviewed and discussed.
PhenAll: Recent breakthroughs in site-selective and direct functionalization of free phenols by transition-metal-catalyzed C-O or C-H bond activation are highlighted here as role models for the complete and switchable positional control of transformations of important core structures.
We summarize a powerful methodology for the alkynylation of C(sp3), C(sp2), and C(sp) carbon atoms, as well as some heteroatoms, with alkynylsulfones. It is based on the fact that β-substituted sulfonylacetylenes undergo unexpected anti-Michael addition of organolithiums and radical species, giving intermediates that evolve into alkynyl derivatives in situ by elimination of the anion or radical TolSO2.
To wit: The title reaction resembles a photoinduced electron-transfer process, and allows the direct formation of medium-sized lactams by C-H activation of the indole nucleus. Therefore it is a versatile tool for the construction of polycyclic indole alkaloid scaffolds.
Chemical power tools: The Fujiwara–Moritani reaction is the palladium-catalyzed coupling reaction of a simple aryl C-H bond with an alkenyl C-H bond to form a new C-C bond (see scheme). This Minireview focuses on the advances in the past five years related to the activation of various aryl C-H bonds in this coupling reaction.
Waste not, want not: The title CDC reactions have emerged as versatile tools for selective and waste-minimized C-C bond formations. They rely on the direct coupling of two different C-H bonds under oxidative conditions. This Review focuses on the recent progress in cross-dehydrogenative Csp3-C formation and provides a comprehensive overview on existing procedures and employed methodologies.
Large Iodine: The site-selective oxidation of unactivated secondary sp3 C-H bonds was accomplished by using a newly defined reactive hypervalent iodine(III) radical in the presence of tert-butyl hydroperoxide (see scheme). Recent studies on hypervalent iodine radicals have significantly contributed to the further development and design of organic molecules in radical oxidation chemistry.
Caught in the cross-fire: This Review highlights the recent developments in catalytic cross-dehydrogenative coupling (CDC) reactions, which join together two aromatic C-H fragments through a palladium-catalyzed dehydrogenative pathway.