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
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).
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.
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 %.
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.
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).
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 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.
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,.
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.
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).
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 by using sequential reactions β-branched amino acids can be obtained.
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.
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 of any additional directing group. An ortho palladation, olefin coordination, and β-migratory insertion sequence has been proposed for the generation of an olefinated intermediate.
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.
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.
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.
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.
The direct ortho alkylation of 8-aminoquinoline-based aryl amides was achieved with primary alkyl bromides in high yields in the presence of an iron catalyst, 1,2-bis(diphenylphosphino)ethane (dppe), and PhMgBr in 2-MeTHF.
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.
Heteroatom-directed C-H borylations of small-ring carbocycles, such as cyclopropanes and cyclobutanes, were achieved with silica-supported monophosphane–Ir catalysts (see scheme). Borylation occurred at the C-H bonds located γ to the directing N or O atoms with exceptional cis stereoselectivity relative to the directing groups (cod=1,5-cyclooctadiene, pin=pinacolato).
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.
Novel urchin-like FeF2 nanoarchitectures have been fabricated by an unconventional nonhomogeneous ionic liquid/diphenyl ether solvothermal method and converted into 3D urchin-like mesoporous α-Fe2O3 nanoarchitectures by solid-state thermal annealing. The α-Fe2O3 nanoarchitectures exhibit good catalytic properties in methane activation reactions.
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.
Getting promoted: The site-selective acyloxylation of aliphatic amides was achieved via a copper-promoted C(sp3)-H bond functionalization process directed by a bidentate ligand. The reaction showed a great preference for activating C-H bonds of β-methyl groups over those of γ-methyl and unactivated methylene groups.
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.
Proof-of-concept for the use of metal antimonates as bifunctional catalysts for oxidative coupling reactions is described. A well-defined zinc(II) antimonate salt enables the α-functionalization of glycine derivatives through a sequential aerobic oxidation-allylation reaction, in which the antimonate anion is responsible for the aerobic oxidation and the zinc cation acts as a Lewis acid for the allylation reaction. EWG=electron-withdrawing group; PMP=p-methoxyphenyl.
By NMR spectroscopy and DFT methods, the mechanism of fluxional exchange in cationic bis(NHC) IrIII systems with an agostic C–H bond and cis-alkyl/hydride ligands is shown to feature an oxidative pathway. Related nonfluxional systems can be “trapped” by the addition of two-electron donors (L), and their stability to C–H reductive elimination can be tuned through the π-acceptor properties of L.
Square deal: A combination of either ruthenium(II) or rhodium(II) complexes and quinine-derived squaramide enables 3-diazooxindoles, indole, and nitroalkenes to undergo a highly efficient asymmetric three-component reaction. Based on this metal/organo relay catalysis, a total synthesis of (−)-folicanthine was accomplished in seven steps with 14.5 % overall yield.
A chance meeting: A rhodium(III)-catalyzed redox-neutral coupling of quinoline N-oxides with alkynes has been realized, thus leading to the synthesis of α-substituted acetophenones. This system integrates C-H activation with O-atom transfer.
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).
C-H activation: A RhIII-catalyzed intramolecular redox-neutral atom-economic annulation of a tethered alkyne has been developed to efficiently construct 2-amidealkyl indoles with completely reversed regioselectivity by a C-H activation pathway (see scheme). A one-pot synthesis of pyrido[1,2-a]indoles has also been developed and applied to a highly efficient formal total synthesis of (±)-goniomitine.
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.
Leukemia ablator: The naturally occurring and highly potent and selective antileukemic agent Δ12-prostaglandin J3 (Δ12-PGJ3) has been assembled through a catalytic, asymmetric, and convergent strategy. The total synthesis renders this precious but rare substance readily available for thorough biological investigations and opens the way for analogue design, synthesis, and biological evaluation.
Gas up: Direct partial oxidation of methane, ethane, and propane to their respective trifluoroacetate (TFA) esters is achieved by a homogeneous hypervalent iodine(III) complex in non-superacidic solvent (HTFA). The reaction is highly selective, and for ethane, greater than 0.5 M Et-TFA can be achieved. Preliminary kinetic analysis and density functional calculations support a nonradical electrophilic CH activation and iodine alkyl functionalization mechanism.
Capturing: Carbon dioxide in the presence of H2 is shown to be an efficient methylating reagent for carbon nucleophiles such as 2-substituted indoles, pyrroles, and electron-rich arenes. Experimental data support the formal capture of formaldehyde. acac=acetylacetonate, triphos=1,1,1-tris(diphenylphosphinomethyl)ethane.
CF3 installation: The direct ortho-trifluoromethylation of arenes including heteroarenes with TMSCF3 has been accomplished by a copper(II)-promoted C-H activation reaction. Mechanistic investigations are consistent with the involvement of C-H activation rather than a simple electrophilic aromatic substitution as the key step. DG=directing group, TMS=trimethylsilyl.
G'day, (carba)mate! A new removable directing group for sp2 C-H activation, the aniline carbamate, is examined in detail. Its utility as a directing group is demonstrated by the ortho-arylation of aniline derivatives under PdII catalysis, with iodonium salts as aryl donors and oxidants. Excellent regio- and chemoselectivity were observed. The directing group can also be easily removed to yield 2-aminobiaryl products (see scheme).
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.
The palladium-catalyzed selective C-H bond trifluoroethylation of aryl iodides allows for an efficient synthesis of a variety of ortho-trifluoroethyl-substituted styrenes. Preliminary mechanistic studies indicate that the reaction might proceed through rate-determining oxidative addition of CF3CH2I to a palladacycle.
In the air: Excellent functional-group tolerance is observed in the title reaction, and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs Co(OAc)2·4 H2O as the catalyst, Mn(OAc)2 as the co-catalyst, and oxygen (from air) as the terminal oxidant. Piv=pivalate.
A catalyst for ether direction: Cleavage of the alkyl C-O bond of aryl ethers is catalyzed by pincer Ir catalysts, without the need for additional reagents, including H2. The corresponding phenols are generated in up to 99 % conversion, with reaction times as short as 1 hour.
Remote access: The first application of an oxalyl amide to direct C-H functionalizations at remote positions is reported. The results show both C(sp2)-H and C(sp3)-H bonds at δ- and ε-positions are effectively activated, thus giving tetrahydroquinolines, benzomorpholines, pyrrolidines, and indolines in moderate to excellent yields by palladium-catalyzed intramolecular C-H amination.
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.
d or s regime? That is the question! A catalyst's orbital electronic regime (see illustration) and bite-angle flexibility are proposed as unifying concepts that serve a more rational design of catalysts. They emerge from quantum-chemical activation strain analyses of 72 different d10-M(L)n model catalyst mediated C-H bond-activation reactions.
Recycling itself! A bio-inspired artificial recycling reaction system has been constructed based on the strategic design of a photoinduced Ce3+–Ce4+ recycling redox reaction, leading to efficient photorecovery of reactants to achieve a reactant-loss-free direct transformation of alkyl C-H bonds on polymer surfaces to form small-molecule groups and polymer brushes (see scheme).
A straightforward one-pot synthetic method including cyclotrimerization, C–H activation, and ring formation to novel hexaferrocenylbenzene is discussed. The electrochemical and spectro-electrochemical behavior as well as a mechanism for the formation of the title compound is reported.
An efficient one-pot synthesis of N-aryl heterocycles by a Cu-catalysed double C–N bond formation is reported. This strategy involves a CuI-catalysed C–N bond-forming reaction between azoles and electron-deficient bromopyridines followed by an intramolecular sp2 C–H amination.
An efficient and general method for the regiospecific synthesis of substituted 2-nitrobenzaldehydes from related benzaldehydes has been developed. The approach involves palladium-catalyzed chelation-assisted C–H nitration as the key step, and enables regiospecific nitration of C–H bonds free from the effect of orientation rules.
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.
Atomic bean counters succeed! An efficient and atom-economical method for the synthesis of substituted indenamines from N-tosylarylimines and alkynes via ruthenium(II)-catalyzed C-H bond activation and annulation is described.
Overcoming strain: A range of valuable 1-indanols and 1-indanamines containing a tertiary C1 atom were synthesized by intramolecular palladium(0)-catalyzed C(sp3)-H arylation (see scheme; PivOK=potassium pivalate). Reactivity and diastereoselectivity differences among the different substrates can be rationalized by conformational analysis.
Methane activation: Methane can be catalytically converted into ethyl propionate upon reaction with ethyl diazoacetate in the presence of highly fluorinated silver complexes as catalysts and by using supercritical carbon dioxide; (scCO2) as the reaction medium (see scheme; TOF=time of flight).
SCF3 building blocks: A unique reaction route allows access to SCF3-functionalized arenes, which are borylated at the ortho-position. The functionalization proceeds by C-H borylation with [Rh(Bpin)(PEt3)3] (pin=pinacolato), and the SCF3 group likely serves as directing group. The generated borylated SCF3 compounds are versatile building blocks for further transformations.
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.
Take from the rich to give to the poor: An heterogeneous Pd catalyst associated to 10 mol % CuCl allows to arylate at C3 of benzo[b]thiophenes using aryl chlorides as the coupling partners, without additional ligands or directing groups. An excellent C3/C2 selectivity was obtained, using electron-rich, electron-poor and also sterically encumbered aryl chlorides.
A great suC=Cess: The oxidative dehydrogenation (ODH) of ethane is a process that enables the production of ethene with high selectivities. Different catalysts and reactor configurations have been developed for this process. This Review focuses on the mechanistic aspects of heterogeneously catalyzed ODH reactions and the main features and common principles of this reaction are discussed.
Robust catalysts: Recently, nitrogen-based ligands have attracted attention with regard to their possible applications in palladium-catalyzed direct C-H arylations because of the unique reactivity of the resulting catalytic systems. This Focus Review examines recent advances in direct C-H arylation of heteroarenes through the use of palladium/nitrogen-based ligand systems.
Put your Trost in this reaction: The first catalytic asymmetric Tsuji–Trost reaction via allylic C-H activation was realized using a new class of chiral phosphoramidite ligands. This work represents a considerable breakthrough in palladium catalyzed asymmetric allylic C-H alkylations.
Activate! Pyrroles, indoles, and carbazoles are among the most important families of nitrogen-containing heterocycles that occur frequently in functional molecules. This Focus Review describes recent advances in transition-metal-catalyzed C-H activation approaches for making these privileged heterocycles. The reactions discussed here showcase the latest developments in organometallic chemistry and homogeneous catalysis.
A bigger piece of the pi: Recently developed organometallic chemistry is powerful and sophisticated enough to modify porphyrin C-H bonds directly, efficiently, and selectively. This Focus Review summarizes examples of direct metalations and C-C bond formation at peripheral porphyrin C-H bonds aiming at improving synthetic strategies for π-electron-rich organic materials.
Cascade reactions realize step-economical syntheses of complex compounds. Palladium catalysts are extremely useful for cascade reactions because they can promote a variety of atom-economical elementary reactions. In this Focus Review, recent advances in palladium-catalyzed atom-economical cascade reactions for the construction of polycyclic compounds are discussed.