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C–H Activation

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

  1. Xiao Chen, Keary M. Engle, Dong-Hui Wang, Jin-Quan Yu*
    Palladium(II)-Catalyzed C–H Activation/C–C Cross-Coupling Reactions: Versatility and Practicality
    Angew. Chem. 2009, 121, 5196–5217; Angew. Chem. Int. Ed. 2009, 48, 5094–5115

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Recent Articles

Grzegorz Filipczyk, Alexander Hildebrandt, Ulrike Pfaff, Marcus Korb, Tobias Rüffer, Heinrich Lang
Combining Cobalt-Assisted Alkyne Cyclotrimerization and Ring Formation through C–H Bond Activation: A “One-Pot” Approach to Complex Multimetallic Structures [Short Communication]

Combining Cobalt-Assisted Alkyne Cyclotrimerization and Ring Formation through C–H Bond Activation: A “One-Pot” Approach to Complex Multimetallic Structures

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.

Eur. J. Inorg. Chem., August 20, 2014, DOI: 10.1002/ejic.201402659

Rhodium(III)-Catalyzed C-C and C-O Coupling of Quinoline N-Oxides with Alkynes: Combination of C-H Activation with O-Atom Transfer

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.

Angew. Chem. Int. Ed., August 14, 2014, DOI: 10.1002/anie.201406747

Chen-Hsun Hung, Parthasarathy Gandeepan, Chien-Hong Cheng
Ruthenium(II)-Catalyzed C-H Bond Activation: An Efficient Route toward Indenamines [Full Paper]

Ruthenium(II)-Catalyzed C-H Bond Activation: An Efficient Route toward Indenamines

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.

ChemCatChem, August 13, 2014, DOI: 10.1002/cctc.201402393

Synthesis of Urchin-Like FeF2 Nanoarchitectures and Their Conversion into Three-Dimensional Urchin-Like Mesoporous α-Fe2O3 Nanoarchitectures for Methane Activation

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.

Eur. J. Inorg. Chem., August 11, 2014, DOI: 10.1002/ejic.201402152

Michael M. Konnick, Brian G. Hashiguchi, Deepa Devarajan, Nicholas C. Boaz, T. Brent Gunnoe, John T. Groves, Niles Gunsalus, Daniel H. Ess, Roy A. Periana
Selective CH Functionalization of Methane, Ethane, and Propane by a Perfluoroarene Iodine(III) Complex [Communication]

Selective CH Functionalization of Methane, Ethane, and Propane by a Perfluoroarene Iodine(III) Complex

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.

Angew. Chem. Int. Ed., August 11, 2014, DOI: 10.1002/anie.201406185

K. C. Nicolaou, Philipp Heretsch, Abdelatif ElMarrouni, Christopher R. H. Hale, Kiran K. Pulukuri, Avinash K. Kudva, Vivek Narayan, K. Sandeep Prabhu
Total Synthesis of Δ12-Prostaglandin J3, a Highly Potent and Selective Antileukemic Agent [Communication]

Total Synthesis of Δ12-Prostaglandin J3, a Highly Potent and Selective Antileukemic Agent

Leukemia ablator: The naturally occurring and highly potent and selective antileukemic agent Δ12-prostaglandin J312-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.

Angew. Chem. Int. Ed., August 5, 2014, DOI: 10.1002/anie.201404917

Ming Shang, Shang-Zheng Sun, Hong-Li Wang, Brian N. Laforteza, Hui-Xiong Dai, Jin-Quan Yu
Exceedingly Fast Copper(II)-Promoted ortho C-H Trifluoromethylation of Arenes using TMSCF3 [Communication]

Exceedingly Fast Copper(II)-Promoted ortho C-H Trifluoromethylation of Arenes using TMSCF3

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.

Angew. Chem. Int. Ed., August 5, 2014, DOI: 10.1002/anie.201404822

A Unified Strategy Towards N-Aryl Heterocycles by a One-Pot Copper-Catalyzed Oxidative C–H Amination of Azoles

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.

Eur. J. Org. Chem., August 5, 2014, DOI: 10.1002/ejoc.201402868

Aniline Carbamates: A Versatile and Removable Motif for Palladium-Catalyzed Directed C-H Activation

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).

Chem. Eur. J., August 5, 2014, DOI: 10.1002/chem.201403712

Brendan M. Monks, Erin R. Fruchey, Silas P. Cook
Iron-Catalyzed C(sp2)-H Alkylation of Carboxamides with Primary Electrophiles [Communication]

Iron-Catalyzed C(sp2)-H Alkylation of Carboxamides with Primary Electrophiles

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.

Angew. Chem. Int. Ed., August 3, 2014, DOI: 10.1002/anie.201406594

Wajid Ali, Srimanta Guin, Saroj Kumar Rout, Anupal Gogoi, Bhisma K. Patel
Thioesterification of Alkylbenzenes with Thiols via Copper- Catalyzed Cross-Dehydrogenative Coupling without a Directing Group [Full Paper]

Lando P. Wolters, Willem-Jan van Zeist, F. Matthias Bickelhaupt
New Concepts for Designing d10-M(L)n Catalysts: d Regime, s Regime and Intrinsic Bite-Angle Flexibility [Full Paper]

New Concepts for Designing d10-M(L)n Catalysts: d Regime, s Regime and Intrinsic Bite-Angle Flexibility

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.

Chem. Eur. J., July 31, 2014, DOI: 10.1002/chem.201403237

Yuehui Li, Tao Yan, Kathrin Junge, Matthias Beller
Catalytic Methylation of C-H Bonds Using CO2 and H2 [Communication]

Catalytic Methylation of C-H Bonds Using CO2 and H2

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.

Angew. Chem. Int. Ed., July 30, 2014, DOI: 10.1002/anie.201405779

Palladium-Catalyzed Cascade C-H Trifluoroethylation of Aryl Iodides and Heck Reaction: Efficient Synthesis of ortho-Trifluoroethylstyrenes

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.

Angew. Chem. Int. Ed., July 27, 2014, DOI: 10.1002/anie.201403793

Johannes Schranck, Anis Tlili, Matthias Beller
Functionalization of Remote C-H Bonds: Expanding the Frontier [Highlight]

Functionalization of Remote C-H Bonds: Expanding the Frontier

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.

Angew. Chem. Int. Ed., July 27, 2014, DOI: 10.1002/anie.201405714

Regiospecific Synthesis of Substituted 2-Nitrobenzaldehydes from Benzaldehydes through Palladium-Catalyzed Chelation-Assisted C–H Nitration

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.

Eur. J. Org. Chem., July 25, 2014, DOI: 10.1002/ejoc.201402451

Michael C. Haibach, Nicholas Lease, Alan S. Goldman
Catalytic Cleavage of Ether C-O Bonds by Pincer Iridium Complexes [Communication]

Catalytic Cleavage of Ether C-O Bonds by Pincer Iridium Complexes

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.

Angew. Chem. Int. Ed., July 24, 2014, DOI: 10.1002/anie.201402576

Cobalt-Catalyzed, Aminoquinoline-Directed C(sp2)-H Bond Alkenylation by Alkynes

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.

Angew. Chem. Int. Ed., July 24, 2014, DOI: 10.1002/anie.201404579

Copper-Promoted Site-Selective Acyloxylation of Unactivated C(sp3)-H Bonds

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.

Chem. Asian J., July 24, 2014, DOI: 10.1002/asia.201402510

Chemoselective Phototransformation of C-H Bonds on a Polymer Surface through a Photoinduced Cerium Recycling Redox Reaction

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 sustainable chemical-modification strategy for the direct transformation of alkyl C-H bonds on polymer surfaces to form small-molecule groups and polymer brushes (see scheme).

Chem. Eur. J., July 23, 2014, DOI: 10.1002/chem.201402786

Chao Wang, Changpeng Chen, Jingyu Zhang, Jian Han, Qian Wang, Kun Guo, Pei Liu, Mingyu Guan, Yingming Yao, Yingsheng Zhao
Easily Accessible Auxiliary for Palladium-Catalyzed Intramolecular Amination of C(sp2)-H and C(sp3)-H Bonds at δ- and ε-Positions [Communication]

Easily Accessible Auxiliary for Palladium-Catalyzed Intramolecular Amination of C(sp2)-H and C(sp3)-H Bonds at δ- and ε-Positions

Remote access: The first application of an oxalyl amide to direct C-H functionalizations at remote positions was reported. The results showed both C(sp2)-H and C(sp3)-H bonds at δ- and ε-positions were effectively activated, thus giving tetrahydroquinolines, benzomorpholines, pyrrolidines, and indolines in moderate to excellent yields by palladium-catalyzed intramolecular C-H amination.

Angew. Chem. Int. Ed., July 22, 2014, DOI: 10.1002/anie.201404854

Jayachandran Jayakumar, Kanniyappan Parthasarathy, Yi-Hsiang Chen, Tai-Hua Lee, Shih-Ching Chuang, Chien-Hong Cheng
One-Pot Synthesis of Highly Substituted Polyheteroaromatic Compounds by Rhodium(III)-Catalyzed Multiple C-H Activation and Annulation [Communication]

One-Pot Synthesis of Highly Substituted Polyheteroaromatic Compounds by Rhodium(III)-Catalyzed Multiple C-H Activation and Annulation

Activated and annulated: A rhodium-catalyzed one-pot synthesis of highly substituted polyheteroaromatic compounds from N-hydroxybenzamidines and alkynes is described. This reaction likely proceeds through multiple C-H bond activation and annulation.

Angew. Chem. Int. Ed., July 17, 2014, DOI: 10.1002/anie.201405183

Shao-Jie Lou, Dan-Qian Xu, Zhen-Yuan Xu
Mild and Versatile Nitrate-Promoted C-H Bond Fluorination [Communication]

Mild and Versatile Nitrate-Promoted C-H Bond Fluorination

Nitrate makes it possible: A novel and facile method for C-H bond fluorination entails remarkably mild reaction conditions (close to room temperature in most cases). Both aromatic and olefinic C(sp2)-H bonds were selectively fluorinated in the presence of a catalytic amount of inexpensive and nontoxic nitrate as the promoter.

Angew. Chem. Int. Ed., July 14, 2014, DOI: 10.1002/anie.201404423

Michael Parmentier, Thomas Hartung, Andreas Pfaltz, Dieter Muri
Iridium-Catalyzed H/D Exchange: Ligand Complexes with Improved Efficiency and Scope [Full Paper]

Iridium-Catalyzed H/D Exchange: Ligand Complexes with Improved Efficiency and Scope

Uses beyond asymmetric catalysis: Iridium complexes with a wide variety of N,P-ligands were explored in hydrogen isotope exchange reactions (see scheme; pyr.=pyridine). Complexes with electron-rich ligands were found to be highly reactive, leading to efficient deuterium incorporation even in compounds bearing only weakly coordinating directing groups.

Chem. Eur. J., July 10, 2014, DOI: 10.1002/chem.201402078

A Practical Approach for the Oxidation of Unactivated Csp3-H Bonds with o-Nitro(diacetoxyiodo)benzene as an Efficient Hypervalent Iodine(III)-Based Oxidizing Agent

A bit hyper: A practical approach for the oxidation of unactivated Csp3-H bonds by o-nitro(diacetoxyiodo)benzene is presented. The nitro group coordinates to the adjacent iodine center through dipolar interaction, which leads to a single substitution of the acetate ligand by tert-butyl hydroperoxide (TBHP). As a result, a strong iodanyl radical is formed, which can activate the inert Csp3-H bonds in a highly efficient manner.

Asian J. Org. Chem., July 2, 2014, DOI: 10.1002/ajoc.201402087

Da-Gang Yu, Francisco de Azambuja, Tobias Gensch, Constantin G. Daniliuc, Frank Glorius
The C-H Activation/1,3-Diyne Strategy: Highly Selective Direct Synthesis of Diverse Bisheterocycles by RhIII Catalysis [Communication]

The C-H Activation/1,3-Diyne Strategy: Highly Selective Direct Synthesis of Diverse Bisheterocycles by RhIII Catalysis

Di-verse: The use of the C-H activation/1,3-diyne general strategy allowed the challenges of selectivity (chemo-, regio-, and mono-/diannulation) to be overcome. This allowed direct construction of diverse polysubstituted bisheterocycles, which are highly important but difficult to access, through the formation of four strategic bonds with high efficiency and high selectivity.

Angew. Chem. Int. Ed., July 1, 2014, DOI: 10.1002/anie.201403782

Davide Ravelli, Matteo Zoccolillo, Mariella Mella, Maurizio Fagnoni
Photocatalytic Synthesis of Oxetane Derivatives by Selective C-H Activation [Communication]

Cycloruthenation of N-(Naphthyl)salicylaldimine and Related Ligands: Utilization of the Ru–C Bond in Catalytic Transfer Hydrogenation

N-(Naphthyl)-4-R-salicylaldimines (R = OCH3, H, Cl; H2L1–H2L3) and 2-hydroxy-N-(naphthyl)naphthaldimine (H2L4) react with [Ru(PPh3)2(CO)2Cl2], undergoing C–H bond activation at the peri position, to afford complexes of the type [Ru(PPh3)2(L)(CO)] (L = L1L4), which can efficiently catalyze the transfer hydrogenation of carbonyl compounds.

Eur. J. Inorg. Chem., June 17, 2014, DOI: 10.1002/ejic.201402236

Frédéric Liron, Julie Oble, Mélanie M. Lorion, Giovanni Poli
Direct Allylic Functionalization Through Pd-Catalyzed C–H Activation [Microreview]

Direct Allylic Functionalization Through Pd-Catalyzed C–H Activation

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.

Eur. J. Org. Chem., May 6, 2014, DOI: 10.1002/ejoc.201402049

Wenjie Liu, Shaohua Wang, Qi Zhang, Jingwen Yu, Jiahe Li, Zhiwei Xie, Hua Cao
Regioselective C3 Alkenylation of 4 H-pyrido[1,2-a]pyrimidin-4-ones via Palladium-Catalyzed C-H Activation [Communication]

Regioselective C3 Alkenylation of 4 H-pyrido[1,2-a]pyrimidin-4-ones via Palladium-Catalyzed C-H Activation

Active ingredient: A new efficient method for the direct alkenylation of 4H-pyrido[1,2-a]pyrimidin-4-ones via palladium-catalyzed C-H bond activation has been developed. This transformation presents a useful approach to functionalize 4H-pyrido[1,2-a]pyrimidin-4-ones, which are privileged structures in many bioactive molecules and versatile synthetic blocks.

Chem. Asian J. 2014, 9, No. 09, 2436-2439

Provas Pal, Arnab Kanti Giri, Harshvardhan Singh, Subhash Chandra Ghosh, Asit Baran Panda
Heterogeneously Porous γ-MnO2-Catalyzed Direct Oxidative Amination of Benzoxazole through C-H Activation in the Presence of O2 [Communication]

Heterogeneously Porous γ-MnO2-Catalyzed Direct Oxidative Amination of Benzoxazole through C-H Activation in the Presence of O2

Sorry for being so direct: The heterogeneously catalyzed direct amination of benzoxazole with a wide range of primary and secondary amines, using molecular oxygen as a green oxidant under mild reaction conditions, is reported. The catalyst can easily be separated by filtration and reused. The 2-aminobenzoxazole products are important skeletons in several biologically active compounds.

Chem. Asian J. 2014, 9, No. 09, 2392-2396

Chihiro Tsukano, Nobusuke Muto, Iderbat Enkhtaivan, Yoshiji Takemoto
Synthesis of Pyrrolophenanthridine Alkaloids Based on C(sp3)-H and C(sp2)-H Functionalization Reactions [Full Paper]

Synthesis of Pyrrolophenanthridine Alkaloids Based on C(sp3)-H and C(sp2)-H Functionalization Reactions

Ring expansion: The alkaloids assoanine (1), pratosine (2), hippadine (3), and dehydroanhydrolycorine (4), which belong to the pyrrolophenanthridine family of alkaloids, have been successfully synthesized by using C-H activation chemistry. The tetracyclic skeletons are constructed in a stepwise manner by C(sp3)-H functionalization and a Catellani reaction involving C(sp2)-H functionalization.

Chem. Asian J. 2014, 9, No. 09, 2628-2634

M. Angeles Fuentes, Andrea Olmos, Bianca K. Muñoz, Kane Jacob, M. Elena González-Núñez, Rossella Mello, Gregorio Asensio, Ana Caballero, Michel Etienne, Pedro J. Pérez
Catalytic Functionalization of Methane and Light Alkanes in Supercritical Carbon Dioxide [Full Paper]

Catalytic Functionalization of Methane and Light Alkanes in Supercritical Carbon Dioxide

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).

Chem. Eur. J. 2014, 20, No. 35, 11013-11018

Catalytic Borylation of SCF3-Functionalized Arenes by Rhodium(I) Boryl Complexes: Regioselective C-H Activation at the ortho-Position

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.

Angew. Chem. Int. Ed. 2014, 53, No. 35, 9311-9315

Simon Janody, Rodolphe Jazzar, Arnaud Comte, Philipp M. Holstein, Jean-Pierre Vors, Mark J. Ford, Olivier Baudoin
Synthesis of 1-Indanols and 1-Indanamines by Intramolecular Palladium(0)-Catalyzed C(sp3)-H Arylation: Impact of Conformational Effects [Full Paper]

Synthesis of 1-Indanols and 1-Indanamines by Intramolecular Palladium(0)-Catalyzed C(sp3)-H Arylation: Impact of Conformational Effects

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.

Chem. Eur. J. 2014, 20, No. 35, 11084-11090

Julia Pedroni, Michele Boghi, Tanguy Saget, Nicolai Cramer
Access to β-Lactams by Enantioselective Palladium(0)-Catalyzed C(sp3)-H Alkylation [Communication]

Access to β-Lactams by Enantioselective Palladium(0)-Catalyzed C(sp3)-H Alkylation

Strain away: Chiral β-lactams are obtained from readily accessible chloroacetamides by an asymmetric palladium(II)-catalyzed C-H functionalization in high yields and excellent enantioselectivities. Important aspects of this transformation are the challenging strain-building C(sp3)-C(sp3) reductive elimination to form the four-membered ring. Ad=adamanyl.

Angew. Chem. Int. Ed. 2014, 53, No. 34, 9064-9067

Yingwei Zhao, Yinjun Xie, Chungu Xia, Hanmin Huang
Palladium-Catalyzed Intramolecular Oxidative C-H Sulfuration of Aryl Thiocarbamates [Communication]

tert-Butyl Nitrite Mediated Regiospecific Nitration of (E)-Azoarenes through Palladium-Catalyzed Directed C-H Activation

Well placed: An efficient protocol for the Pd-catalyzed regiospecific ortho-nitration of (E)-azoarenes has been achieved by using tBuONO as a nitrating agent under atmospheric oxygen. A series of both symmetrical and unsymmetrical azoarenes were nitrated efficiently by this procedure, providing excellent chemo- and regioselectivity and compatibility with a broad array of functional groups.

Chem. Eur. J. 2014, 20, No. 32, 9862-9866

Exploring Bis(cyclometalated) Ruthenium(II) Complexes as Active Catalyst Precursors: Room-Temperature Alkene–Alkyne Coupling for 1,3-Diene Synthesis

C-H activation: The ruthenium catalyst 1 promoted coupling between acrylic esters and amides with internal alkynes to form 1,3-diene products at room temperature. A proposed catalytic cycle involves C-C bond formation by oxidative cyclization, β-hydride elimination, and C-H bond reductive elimination.

Angew. Chem. Int. Ed. 2014, 53, No. 32, 8437-8440

Kedong Yuan, Julien Boixel, Agisilaos Chantzis, Denis Jacquemin , Véronique Guerchais, Henri Doucet
Benzothiophene or Benzofuran Bridges in Diaryl Ethenes: Two-Step Access by Pd-Catalyzed C-H Activation and Theoretical/Experimental Studies on Their Photoreactivity [Full Paper]

Benzothiophene or Benzofuran Bridges in Diaryl Ethenes: Two-Step Access by Pd-Catalyzed C-H Activation and Theoretical/Experimental Studies on Their Photoreactivity

A series of terarylenes incorporating a benzothiophene or a benzofuran as the central ethene unit was synthesized by means of sequential Pd-catalysed C-H activation reactions (see figure). This new methodology allows easy modification of the nature of the pendant heteroarene groups. A study on their photochromic properties revealed that the natures of the heteroarene nature and the central unit drastically modify their photochromic behavior.

Chem. Eur. J. 2014, 20, No. 32, 10073-10083

Dmitry Katayev, Kai F. Pfister, Timo Wendling, Lukas J. Gooßen
Copper-Mediated ortho-Nitration of (Hetero)Arenecarboxylates [Communication]

Copper-Mediated ortho-Nitration of (Hetero)Arenecarboxylates

Mild and selective: In the presence of [CuNO3(PPh3)2], aromatic and heteroaromatic 8-aminoquinolinyl amides undergo selective ortho-C-H nitration under exceptionally mild conditions. A microwave-assisted cleavage of the amide directing group allows regeneration of the carboxylate group within minutes. The carboxylate may be tracelessly removed in situ, or substituted by aryl or alkoxy groups in decarboxylative processes (see scheme; NH2Q=8-aminoquinoline, X=CO2H, H, Ar, OR).

Chem. Eur. J. 2014, 20, No. 32, 9902-9905

Iridium-Catalyzed Regioselective Silylation of Aromatic and Benzylic C-H Bonds Directed by a Secondary Amine

A 'SiN'ch: In the title reaction of benzylamines or anilines, (hydrido)silyl amines are generated in situ which undergo selective silylation at the C-H bond γ to the amino group. The silylation products can be further functionalized through oxidation, halogenation, and cross-coupling reactions. cod=1,5-cyclooctadiene, nbe=norbornene.

Angew. Chem. Int. Ed. 2014, 53, No. 32, 8471-8474

Laurent Djakovitch, François-Xavier Felpin
Direct C sp2-H and C sp3-H Arylation Enabled by Heterogeneous Palladium Catalysts [Minireview]

Direct C sp2-H and C sp3-H Arylation Enabled by Heterogeneous Palladium Catalysts

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.

ChemCatChem 2014, 6, No. 08, 2175-2187

Jamal Koubachi, Saïd El Kazzouli, Mosto Bousmina, Gérald Guillaumet
Functionalization of Imidazo[1,2-a]pyridines by Means of Metal-Catalyzed Cross-Coupling Reactions [Microreview]

Functionalization of Imidazo[1,2-a]pyridines by Means of Metal-Catalyzed Cross-Coupling Reactions

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.

Eur. J. Org. Chem. 2014, No. 24, 5119-5138

Facile Access to 1H-Indazoles through Iodobenzene-Catalyzed C–H Amination under Mild, Transition-Metal-Free Conditions

Transition-metal- and halogen-free synthesis of N-aryl-substituted 1H-indazole and derivatives is accomplished on the basis of the iodobenzene-catalyzed intramolecular C–H amination of hydrazones in the presence of Oxone in trifluoroacetic acid at –10 °C. The 1H-indazole derivatives are obtained in moderate to good yields (up to 90 %).

Eur. J. Org. Chem. 2014, No. 22, 4720-4723

Ligands Control Reactivity and Selectivity in Palladium-Catalyzed Functionalization of Unactivated C sp3-H Bonds

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.

ChemCatChem 2014, 6, No. 08, 2188-2190

Hamad H. Al Mamari, Emelyne Diers, Lutz Ackermann
Triazole-Assisted Ruthenium-Catalyzed C-H Arylation of Aromatic Amides [Full Paper]

Triazole-Assisted Ruthenium-Catalyzed C-H Arylation of Aromatic Amides

Assisting activation: Ruthenium(II)-catalyzed C-H arylations of (hetero)arenes and alkenes have been achieved with aryl halides through removable bidentate auxiliaries derived from modular 1,2,3-triazoles (see scheme; TAM=triazolyldimethylmethyl).

Chem. Eur. J. 2014, 20, No. 31, 9739-9743

Modular Synthesis of Phenanthro[9,10-c]thiophenes by a Sequence of C-H Activation, Suzuki Cross-Coupling and Photocyclization Reactions

Three C-C bond formation reactions are successively coupled in a convergent synthesis of phenanthro[9,10-c]thiophenes A. The key reaction is an unprecedented photocyclization of precursors B, which proceeds cleanly at λ=254 nm (60–82 % yield). Diarylthiophenes B are conveniently assembled employing a sequence of oxidative and regular Suzuki cross-coupling reactions.

Chem. Eur. J. 2014, 20, No. 31, 9725-9732

Asymmetric Synthesis of Isoindolones by Chiral Cyclopentadienyl-Rhodium(III)-Catalyzed C-H Functionalizations

Heterocycle synthesis: Chiral isoindolones are obtained by rhodium(III)-catalyzed enantioselective reactions of aryl hydroxamates with alkyl-substituted diazo esters through C-H functionalization under mild conditions. Chiral cyclopentadienyl ligands with a biaryl backbone lead to excellent enantioselectivities.

Angew. Chem. Int. Ed. 2014, 53, No. 30, 7896-7899

Direct Functionalization with Complete and Switchable Positional Control: Free Phenol as a Role Model

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.

Angew. Chem. Int. Ed. 2014, 53, No. 30, 7710-7712

Jaika Dörfler, Till Preuß, Alexandra Schischko, Marc Schmidtmann, Sven Doye
A 2,6-Bis(phenylamino)pyridinato Titanium Catalyst for the Highly Regioselective Hydroaminoalkylation of Styrenes and 1,3-Butadienes [Communication]

A 2,6-Bis(phenylamino)pyridinato Titanium Catalyst for the Highly Regioselective Hydroaminoalkylation of Styrenes and 1,3-Butadienes

Linear progress: A new Ti complex with 2,6-bis(phenylamino)pyridinato ligands catalyzes highly regioselective hydroaminoalkylation reactions of styrenes. The process that directly gives access to the corresponding linear hydroaminoalkylation products offers a new and flexible synthetic approach towards pharmaceutically important 3-arylpropylamines. It is also possible to convert (E)-1-phenyl-1,3-butadienes into the corresponding linear products.

Angew. Chem. Int. Ed. 2014, 53, No. 30, 7918-7922

Silylative Coupling versus Metathesis—Efficient Methods for the Synthesis of Difunctionalized Double-Decker Silsesquioxane Derivatives

Divinyl-substituted double-decker silsesquioxanes (DDSQ-2SiVi) have been functionalized by a highly effective silylative coupling and/or metathesis with olefins. Both reactions proceed highly stereoselectively and lead to nearly quantitative formation of E isomers. Preliminary studies on the silylative coupling of DDSQ-2SiVi with 1,4-divinylbenzene resulted in a stereoregular cooligomer containing double-decker (silsesquioxyl-silylene)-vinylene-phenylene units.

Chem. Eur. J. 2014, 20, No. 30, 9387-9393

Yasuaki Kawaguchi, Shigeo Yasuda, Akira Kaneko, Yuki Oura, Chisato Mukai
Rhodium(I)-Catalyzed Cycloisomerization of Benzylallene-Alkynes through C-H Activation [Communication]

Rhodium(I)-Catalyzed Cycloisomerization of Benzylallene-Alkynes through C-H Activation

Vinylidene complex: An efficient RhI-catalyzed cycloisomerization of benzylallene-alkynes produced the tricyclo[9.4.0.03,8]pentadecapentaene skeleton through Csp2-H bond activation. Based on deuteration and competition experiments, a reaction mechanism was proposed, which proceeds via a vinylidenecarbene–RhI intermediate.

Angew. Chem. Int. Ed. 2014, 53, No. 29, 7608-7612

Synthesis of Spirocyclic Enones by Rhodium-Catalyzed Dearomatizing Oxidative Annulation of 2-Alkenylphenols with Alkynes and Enynes

Inspiroing dearomatization: The dearomatizing oxidative annulation of 2-alkenylphenols with alkynes and enynes proceeds with high yields and regioselectivities under RhIII catalysis (see scheme). These reactions are successful using Cu(OAc)2 or air as the stoichiometric oxidant, and provide spirocyclic enones. Application of this process to the preparation of a highly functionalized tetracycle is also demonstrated (Ac=acetyl).

Chem. Eur. J. 2014, 20, No. 28, 8599-8602

Marie-Aude Hiebel, Yacoub Fall, Marie-Christine Scherrmann, Sabine Berteina-Raboin
Straightforward Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines in PEG400 Medium through One-Pot Condensation and C–H Arylation [Full Paper]

Straightforward Synthesis of Various 2,3-Diarylimidazo[1,2-a]pyridines in PEG400 Medium through One-Pot Condensation and C–H Arylation

PEG400 was found to be a suitable solvent for condensation of various 2-amino pyridines with α-bromo ketones. 2-Arylimidazo[1,2-a]pyridines were obtained in a short time through microwave irradiation. A combination of the previous condensation with a C–H arylation reaction was developed to access various 2,3-diarylimidazo[1,2-a]pyridines with a reduced amount of palladium catalyst and no ligand.

Eur. J. Org. Chem. 2014, No. 21, 4643-4650

Daiki Tanaka, Shota Tanaka, Atsunori Mori
Palladium-Catalyzed α-Arylation of Carboxylic Acid Derivatives with Grignard Reagent [Short Communication]

Palladium-Catalyzed α-Arylation of Carboxylic Acid Derivatives with Grignard Reagent

Functionalization at the C–H bond of α-arylcarboxylic acids with a Grignard reagent results in metalation. Treatment of the metalated intermediates with aryl halides in the presence of a Pd catalyst leads to diarylcarboxylic acids in good to excellent yields through the formation of a C(sp3)–C(sp2) bond. The use of the Grignard reagent is the key to a successful coupling reaction.

Eur. J. Org. Chem. 2014, No. 20, 4254-4257

Xiaolan Chen, Xu Li, Zhibo Qu, Diandian Ke, Lingbo Qu, Likun Duan, Wenpeng Mai, Jinwei Yuan, Jianyu Chen, Yufen Zhao
H-Phosphonate-Mediated Amination of Quinoline N-Oxides with Tertiary Amines: A Mild and Metal-Free Synthesis of 2-Dialkylaminoquinolines [Communication]

C-C Coupling Through Intramolecular Dual C-H Activation Directed by a Removable Carboxylate Group: A Method for the Synthesis of Fluorenones under Mild Reaction Conditions

I challenge you to a dual! An intramolecular oxidative coupling reaction that uses carboxyl-group-directed dual C-H bond activation catalyzed by palladium has been developed. In this reaction, the use of diphenylacetic acid and their derivatives as substrates gives substituted fluorenones in high yields. This method offers a highly favorable synthetic pathway to efficiently build a variety of substituted fluorenones.

Asian J. Org. Chem. 2014, 3, No. 06, 695-699

Yan Li, Yun Wu, Guang-Shui Li, Xi-Sheng Wang
Palladium-Catalyzed C-F Bond Formation via Directed C-H Activation [Review]

Christoph Kornhaaß, Christian Kuper, Lutz Ackermann
Ferrocenylalkynes for Ruthenium-Catalyzed Isohypsic C-H/N-O Bond Functionalizations [Update]

Suman De Sarkar, Weiping Liu, Sergei I. Kozhushkov, Lutz Ackermann
Weakly Coordinating Directing Groups for Ruthenium(II)- Catalyzed C-H Activation [Review]

Zhao-Lei Yan, Wen-Liang Chen, Ya-Ru Gao, Shuai Mao, Yan-Lei Zhang, Yong-Qiang Wang
Palladium-Catalyzed Intermolecular C-2 Alkenylation of Indoles Using Oxygen as the Oxidant [Update]

José Luis García Ruano, José Alemán, Alejandro Parra, Leyre Marzo
Sulfonyl Acetylenes as Alkynylating Reagents Under Radical or Anionic Conditions [Microreview]

Sulfonyl Acetylenes as Alkynylating Reagents Under Radical or Anionic Conditions

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.

Eur. J. Org. Chem. 2014, No. 08, 1577-1588

Philipp J. Gritsch, Christian Leitner, Magnus Pfaffenbach, Tanja Gaich
The Witkop Cyclization: A Photoinduced C-H Activation of the Indole System [Minireview]

The Witkop Cyclization: A Photoinduced C-H Activation of the Indole System

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.

Angew. Chem. Int. Ed. 2014, 53, No. 05, 1208-1217

Towards Ideal Synthesis: Alkenylation of Aryl C-H Bonds by a Fujiwara–Moritani Reaction

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.

Chem. Eur. J. 2014, 20, No. 03, 634-642

The Cross-Dehydrogenative Coupling of Csp3-H Bonds: A Versatile Strategy for C-C Bond Formations

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.

Angew. Chem. Int. Ed. 2014, 53, No. 01, 74-100

New Site-Selective Organoradical Based on Hypervalent Iodine Reagent for Controlled Alkane sp3 C-H Oxidations

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.

ChemCatChem 2014, 6, No. 01, 76-78

Yinuo Wu, Jun Wang, Fei Mao, Fuk Yee Kwong
Palladium-Catalyzed Cross-Dehydrogenative Functionalization of C(sp2)-H Bonds [Focus Review]

Palladium-Catalyzed Cross-Dehydrogenative Functionalization of C(sp2)-H Bonds

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.

Chem. Asian J. 2014, 9, No. 01, 26-47

© Wiley-VCH 2013.