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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

Linda S. Jongbloed, Bas de Bruin, Joost N. H. Reek, Martin Lutz, Jarl Ivar van der Vlugt
Facile Synthesis and Versatile Reactivity of an Unusual Cyclometalated Rhodium(I) Pincer Complex [Full Paper]

Facile Synthesis and Versatile Reactivity of an Unusual Cyclometalated Rhodium(I) Pincer Complex

MC Flex: A flexidentate PN(C) scaffold amenable to acting as either a bi- or tridentate ligand to a RhI center is described. Tridentate coordination involves facile aromatic C-H activation to generate a rare low-valent RhI metallacycle. The formation of a C-H agostic complex, dual-mode ligand reactivity, and the synthesis of the corresponding RhIII–diiodide complex is discussed.

Chem. Eur. J., March 24, 2015, DOI: 10.1002/chem.201406463

Neeraj Kumar Mishra, Taejoo Jeong, Satyasheel Sharma, Youngmi Shin, Sangil Han, Jihye Park, Joa Sub Oh, Jong Hwan Kwak, Young Hoon Jung, In Su Kim
Rhodium(III)-Catalyzed Selective C-H Cyanation of Indolines and Indoles with an Easily Accessible Cyano Source [Update]

Palladium-Catalyzed C-H Activation of N-Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza-1,3-Dienes

Making one into two: Palladium-catalyzed direct C(sp3)-H activation of an N-allyl imine led to the generation of an all-carbon π-allyl complex which presumably remains in equilibrium with a rare 2-aza π-allyl species. Nucleophilic attack on the π-allyl intermediates gave either a 1-aza-1,3-diene or 2-aza-1,3-diene in a completely regioselective manner.

Angew. Chem. Int. Ed., March 24, 2015, DOI: 10.1002/anie.201501322

Ganesh Chandra Nandi, Sudhakar Rao Kota, Tricia Naicker, Thavendran Govender, Hendrick G. Kruger, Per I. Arvidsson
Cu(OAc)2-Catalysed Oxidative Dual C–H/N–H Activation of Terminal Alkynes and N-Deprotected Sulfonimidamides: An Easy Access to N-Alkynylated Sulfonimidamides [Full Paper]

Cu(OAc)2-Catalysed Oxidative Dual C–H/N–H Activation of Terminal Alkynes and N-Deprotected Sulfonimidamides: An Easy Access to N-Alkynylated Sulfonimidamides

N-Alkynylated sulfonimidamides have been synthesised through the CuII-catalysed N–H/C–H activation reaction of N-deprotected sulfonimidamides and terminal alkynes. The resulting N-alkynylated sulfonimidamides react with SiO2 or BH3·SMe2 to give the corresponding carbonyl or alkyl derivative, respectively.

Eur. J. Org. Chem., March 17, 2015, DOI: 10.1002/ejoc.201500239

Tandem Catalytic C(sp3)-H Amination/Sila-Sonogashira–Hagihara Coupling Reactions with Iodine Reagents

I(003) is a double agent: A tandem C-N and C-C bond-forming reaction has been achieved through RhII/Pd0 catalysis. The sequence first involves an iodine(III) oxidant, then the in situ generated iodine(I) by-product is used as a coupling partner. The overall process affords complex building blocks with high yields, and demonstrates the synthetic value of iodoarenes produced in trivalent iodine reagent mediated oxidations.

Angew. Chem. Int. Ed., March 17, 2015, DOI: 10.1002/anie.201412364

Gang Li, Chunqi Jia, Qingliang Chen, Kai Sun, Feng Zhao, Hankui Wu, Zhiyong Wang, Yunhe Lv, Xiaolan Chen
Copper(I)-Catalyzed Dehydrogenative Amidation of Arenes Using Air as the Oxidant [Update]

Rhodium(I)-Catalyzed Regiospecific Dimerization of Aromatic Acids: Two Direct C-H Bond Activations in Water

On the double: An efficient, regiospecific, and general oxidative dimerization of simple aryl acids to generate diaryl acids was developed. The reaction involves two direct aryl C-H activations catalyzed by rhodium, uses water as the solvent, and can be easily scaled up. The natural product ellagic acid was obtained in only two steps by using this method.

Angew. Chem. Int. Ed., March 12, 2015, DOI: 10.1002/anie.201500220

Pd-Catalyzed C-H Activation: Expanding the Portfolio of Metal-Catalyzed Functionalization of Unreactive C-H Bonds by Arene–Chromium π-Complexation

Switch it on: η6-arene–transition-metal complexes are significant intermediates in organic chemistry; however, their use in C-H functionalization remain largely unexplored. Recently, new methodologies for the Pd-catalyzed C-H activation of unreactive sp2 and sp3 bonds that rely on the efficient activation of arenes by π-complexation have been developed. These reactions significantly expand the toolbox of modern C-H activation methods.

ChemCatChem, March 10, 2015, DOI: 10.1002/cctc.201500080

Synthesis of Dibenzo[c,e]oxepin-5(7H)-ones from Benzyl Thioethers and Carboxylic Acids: Rhodium-Catalyzed Double C-H Activation Controlled by Different Directing Groups

Double crossed! Reported is the rhodium(III)-catalyzed double C-H cross-coupling of benzyl thioethers and carboxylic acids. Two directing groups (DGs) are used to enhance the selectivity of the double C-H activation. One DG becomes part of the product and the other is removed in situ.

Angew. Chem. Int. Ed., March 10, 2015, DOI: 10.1002/anie.201500486

Ning Jin, Changduo Pan, Honglin Zhang, Pan Xu, Yixiang Cheng, Chengjian Zhu
Rhodium-Catalyzed Direct C7 Alkynylation of Indolines [Communication]

Synthesis of a Double Helicene by a Palladium-Catalyzed Cross-Coupling Reaction: Structure and Physical Properties

Do the twist again! A twisted π-extended double helicene was synthesized through a palladium-catalyzed coupling reaction. X-ray crystallography revealed grossly twisted structures that were soluble in various conventional organic solvents. Electrochemical properties were also studied by measurements of cyclic voltammetry, which revealed its HOMO and LUMO energies (see scheme).

Chem. Eur. J., March 5, 2015, DOI: 10.1002/chem.201500074

Ruthenium as a Single Catalyst for Two Steps: One-Pot Ruthenium(II)-Catalyzed Aerobic Oxidative Dehydrogenation of Dihydroquinazolinones and Cross-Coupling/Annulation to give N-Fused Polycyclic Heteroarenes

One catalyst fits all: One single catalyst, [RuCl2(p-cymene)]2, was used for oxidative dehydrogenation followed by cross-coupling/annulation reactions to access diversely decorated N-fused polycyclic heteroarenes from dihydroquinazolinones and alkynes. DCE=1,2-dichloroethane.

Asian J. Org. Chem., March 4, 2015, DOI: 10.1002/ajoc.201500025

Svenja Warratz, Christoph Kornhaaß, Ana Cajaraville, Benedikt Niepötter, Dietmar Stalke, Lutz Ackermann
Ruthenium(II)-Catalyzed C-H Activation/Alkyne Annulation by Weak Coordination with O2 as the Sole Oxidant [Communication]

Ruthenium(II)-Catalyzed C-H Activation/Alkyne Annulation by Weak Coordination with O2 as the Sole Oxidant

Air and water: Ruthenium(II) biscarboxylates allow for the annulation of alkynes and alkenes by oxidative C-H functionalizations with molecular oxygen as the sole oxidant. The C-H/O-H functionalization process occurs with excellent selectivities under mild reaction conditions, with water produced as the only by-product.

Angew. Chem. Int. Ed., March 3, 2015, DOI: 10.1002/anie.201500600

Jilai Li, Xiao-Nan Wu, Maria Schlangen, Shaodong Zhou, Patricio González-Navarrete, Shiya Tang, Helmut Schwarz
On the Role of the Electronic Structure of the Heteronuclear Oxide Cluster [Ga2Mg2O5].+ in the Thermal Activation of Methane and Ethane: An Unusual Doping Effect [Communication]

On the Role of the Electronic Structure of the Heteronuclear Oxide Cluster [Ga2Mg2O5].+ in the Thermal Activation of Methane and Ethane: An Unusual Doping Effect

Bridging oxygen: A combination of mass spectrometry and quantum chemical calculations shows that [Ga2Mg2O5].+, bearing an unpaired electron at a bridging oxygen atom, is capable of activating the C-H bond of methane. The roles of spin density and charge distributions in hydrogen-atom transfer processes provide important guidance for the rational design of catalysts.

Angew. Chem. Int. Ed., February 27, 2015, DOI: 10.1002/anie.201412441

Feihua Luo, Jun Yang, Zhengkai Li, Haifeng Xiang, Xiangge Zhou
Palladium-Catalyzed C–H Bond Acylation of Acetanilides with Benzylic Alcohols under Aqueous Conditions [Full Paper]

Palladium-Catalyzed C–H Bond Acylation of Acetanilides with Benzylic Alcohols under Aqueous Conditions

Palladium-catalyzed dehydrogenative coupling reactions between acetanilides and benzylic alcohols under aqueous conditions are reported. A wide range of benzophenone derivatives could be obtained in good to excellent yields up to 98 %. Mechanism studies showed that a bimetallic palladium cyclopalladated complex might be involved in the catalysis.

Eur. J. Org. Chem., February 25, 2015, DOI: 10.1002/ejoc.201500016

A General and Scalable Synthesis of Aeruginosin Marine Natural Products Based on Two Strategic C(sp3)-H Activation Reactions

Family ties: An efficient access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, was achieved. The strategic use of two different C(sp3)-H activation reactions led to the synthesis of aeruginosins 98B and 298 A, with the latter being obtained on an unprecedentedly large scale.

Angew. Chem. Int. Ed., February 25, 2015, DOI: 10.1002/anie.201500066

Peter Finkbeiner, Ulrich Kloeckner, Boris J. Nachtsheim
OH-Directed Alkynylation of 2-Vinylphenols with Ethynyl Benziodoxolones: A Fast Access to Terminal 1,3-Enynes [Communication]

OH-Directed Alkynylation of 2-Vinylphenols with Ethynyl Benziodoxolones: A Fast Access to Terminal 1,3-Enynes

TIPS and tricks for alkynylation: The first direct alkynylation of 2-vinylphenols was developed. The rationally optimized hypervalent iodine reagent TIPS-EBX* (see scheme)in combination with [(Cp*RhCl2)2] as a C-H-activating transition metal catalyst enables the construction of a variety of highly substituted 1,3-enynes in high yield under mild conditions and with excellent chemo- and stereoselectivity.

Angew. Chem. Int. Ed., February 23, 2015, DOI: 10.1002/anie.201412148

Dongbing Zhao, Ju Hyun Kim, Linda Stegemann, Cristian A. Strassert, Frank Glorius
Cobalt(III)-Catalyzed Directed C-H Coupling with Diazo Compounds: Straightforward Access towards Extended π-Systems [Communication]

Cobalt(III)-Catalyzed Directed C-H Coupling with Diazo Compounds: Straightforward Access towards Extended π-Systems

Co-catalyzed! The first highly efficient and scalable cobalt-catalyzed directed C-H functionalization with carbene precursors is presented. This methodology provides a modular route towards a new class of conjugated polycyclic hydrocarbons with tunable emission wavelengths.

Angew. Chem. Int. Ed., February 20, 2015, DOI: 10.1002/anie.201411994

Shuai Xu, Guojiao Wu, Fei Ye, Xi Wang, Huan Li, Xia Zhao, Yan Zhang, Jianbo Wang
Copper(I)-Catalyzed Alkylation of Polyfluoroarenes through Direct C-H Bond Functionalization [Communication]

Copper(I)-Catalyzed Alkylation of Polyfluoroarenes through Direct C-H Bond Functionalization

Along came “Poly”: C(sp2)-C(sp3) bond formation through direct C-H functionalization proceeds through a copper(I)-catalyzed alkylation of electron-poor polyfluoroarenes with N-tosylhydrazones or diazo compounds. The transformation represents a highly efficient practical method for the direct alkylation of polyfluoroarenes. phen=1,10-phenanthroline, Ts=4-toluenesulfonyl.

Angew. Chem. Int. Ed., February 17, 2015, DOI: 10.1002/anie.201412450

Lara Ferrighi, Igor Píš, Thanh Hai Nguyen, Mattia Cattelan, Silvia Nappini, Andrea Basagni, Matteo Parravicini, Antonio Papagni, Francesco Sedona, Elena Magnano, Federica Bondino, Cristiana Di Valentin, Stefano Agnoli
Control of the Intermolecular Coupling of Dibromotetracene on Cu(110) by the Sequential Activation of C-Br and C-H Bonds [Full Paper]

Control of the Intermolecular Coupling of Dibromotetracene on Cu(110) by the Sequential Activation of C-Br and C-H Bonds

Scratching the surface: Easy control of the intermolecular coupling of 5,11-dibromotetracene on a Cu(110) surface by temperature has been achieved. Organometallic oligomers characterized by copper atoms that bridge the tetracene molecule in the 5,11 positions are formed at mild temperature (room temperature to 523 K), whereas the higher intrinsic stability of the radical sites at the 3,2 and 8,9 positions determines the formation of linear chains produced by C-C coupling between the ends of the molecules at higher temperature (see picture).

Chem. Eur. J. 2015, 21, No. 15, 5826-5835

Cobalt-Catalyzed C-H Arylations with Weakly-Coordinating Amides and Tetrazoles: Expedient Route to Angiotensin-II-Receptor Blockers

Broadly applicable cobalt-catalyzed C-H arylations with weakly-coordinating amides or tetrazoles provided step-economical access to biaryl tetrazoles as key structural motifs of angiotensin-II-receptor blockers (ARBs), such as the blockbuster drug Losartan (see scheme).

Chem. Eur. J. 2015, 21, No. 15, 5718-5722

Ji-Cheng Zhang, Jiang-Ling Shi, Bi-Qin Wang, Ping Hu, Ke-Qing Zhao, Zhang-Jie Shi
Direct Oxidative Arylation of Aryl C-H Bonds with Aryl Boronic Acids via Pd Catalysis Directed by the N,N-Dimethylaminomethyl Group [Communication]

Direct Oxidative Arylation of Aryl C-H Bonds with Aryl Boronic Acids via Pd Catalysis Directed by the N,N-Dimethylaminomethyl Group

Getting the skeleton right: Biaryl skeletons were directly constructed via palladium-catalyzed ortho-arylation of N,N-dimethyl benzylamine with aryl boronic acids under open-flask conditions. The N,N-dimethylaminomethyl group was first applied as a directing group in such an oxidative coupling. Various substrates proved to be efficient coupling partners, furnishing the corresponding ortho-monoarylated or -diarylated arenes in moderate to good yields under mild conditions.

Chem. Asian J. 2015, 10, No. 04, 840-843

Transition-Metal-Catalyzed π-Bond-Assisted C-H Bond Functionalization: An Emerging Trend in Organic Synthesis

Piece of pi: Transition-metal-catalyzed directing-group-assisted C-H activation reactions play an indispensable role in organic synthesis. Most directing groups interact with metals through the σ coordination of their lone pairs, yet π-bond directing groups also exist (see figure). The π-coordination-assisted C-H bond functionalization reactions are summarized.

Chem. Asian J. 2015, 10, No. 04, 824-838

Manfred Manßen, Nicolai Lauterbach, Jaika Dörfler, Marc Schmidtmann, Wolfgang Saak, Sven Doye, Rüdiger Beckhaus
Efficient Access to Titanaaziridines by C-H Activation of N-Methylanilines at Ambient Temperature [Communication]

Efficient Access to Titanaaziridines by C-H Activation of N-Methylanilines at Ambient Temperature

Killing two birds with one stone: A bis(η51-pentafulvene)titanium complex reacts with secondary N-methylamines resulting in simultaneous N-H and C-H activation and formation of titanaaziridines. These reactions can even be performed below room temperature und generate three-membered titanacycles. The first molecular structure of a titanium methyleneaniline complex is determined.

Angew. Chem. Int. Ed. 2015, 54, No. 14, 4383-4387

Carina Sollert, Karthik Devaraj, Andreas Orthaber, Paul J. Gates, Lukasz T. Pilarski
Ru-Catalysed C-H Arylation of Indoles and Pyrroles with Boronic Acids: Scope and Mechanistic Studies [Full Paper]

Ru-Catalysed C-H Arylation of Indoles and Pyrroles with Boronic Acids: Scope and Mechanistic Studies

High tolerance: An oxidative, Ru-catalysed, and highly selective C-H arylation of indoles and pyrroles is accomplished by using boronic acids (see picture; pym=2-pyrimidyl). The reaction tolerates a wide range of functional groups, including aryl iodides and tryptophan derivatives. New indole-based ruthenacycles are described and their role in the mechanism is investigated.

Chem. Eur. J. 2015, 21, No. 14, 5380-5386

Lin He, Kishore Natte, Jabor Rabeah, Christoph Taeschler, Helfried Neumann, Angelika Brückner, Matthias Beller
Heterogeneous Platinum-Catalyzed C-H Perfluoroalkylation of Arenes and Heteroarenes [Communication]

Heterogeneous Platinum-Catalyzed C-H Perfluoroalkylation of Arenes and Heteroarenes

Platinum level: The efficient and versatile title reaction is based on the radical reactivity of perfluoroalkyl halides. The ready availability of the starting materials, the excellent substrate tolerance, and the reusability of catalyst make this protocol attractive for the economic synthesis of perfluoroalkyl-group-substituted aromatic compounds.

Angew. Chem. Int. Ed. 2015, 54, No. 14, 4320-4324

Hao Wu, Zhiwei Xiao, Junhui Wu, Yong Guo, Ji-Chang Xiao, Chao Liu, Qing-Yun Chen
Direct Trifluoromethylthiolation of Unactivated C(sp3)-H Using Silver(I) Trifluoromethanethiolate and Potassium Persulfate [Communication]

Direct Trifluoromethylthiolation of Unactivated C(sp3)-H Using Silver(I) Trifluoromethanethiolate and Potassium Persulfate

Direct and mild: A variety of alkyltrifluoromethylthioethers were efficiently synthesized by direct trifluoromethylthiolation of unactivated C(sp3)-H bonds under mild reaction conditions. The reagent system comprises AgSCF3 and K2S2O8, the latter of which both activates the C(sp3)-H bond and oxidizes AgSCF3. The reaction has a broad substrate scope with good functional-group tolerance and good selectivity.

Angew. Chem. Int. Ed. 2015, 54, No. 13, 4070-4074

Pd-Catalyzed Csp2-H Functionalization of Heteroarenes via Isocyanide Insertion: Concise Synthesis of Di-(Hetero)Aryl Ketones and Di-(Hetero)Aryl Alkylamines

Functionalized azoles: Pd-catalyzed direct C-H bond functionalization of heteroarenes via an isocyanide insertion strategy (see scheme) for the synthesis of di-(hetero)aryl ketones and di-(hetero)aryl alkylamines is described.

Chem. Eur. J. 2015, 21, No. 13, 4908-4912

Shuaibo Guo, Yaxuan Li, Yu Wang, Xin Guo, Xu Meng, Baohua Chen
Iron-Catalyzed Cross Dehydrogenative Coupling (CDC) of Indoles and Benzylic C-H Bonds [Communication]

Weiping Liu, Daniel Zell, Michael John, Lutz Ackermann
Manganese-Catalyzed Synthesis of cis-β-Amino Acid Esters through Organometallic C-H Activation of Ketimines [Communication]

Manganese-Catalyzed Synthesis of cis-β-Amino Acid Esters through Organometallic C-H Activation of Ketimines

An operationally simple manganese-catalyzed C-H functionalization of ketimines provides access to β-amino acid esters. The mechanism of this transformation was studied, and its utility proven by further modifications of the synthetically useful β-amino acid esters into attractive compounds.

Angew. Chem. Int. Ed. 2015, 54, No. 13, 4092-4096

Shuo Guo, Xiaofei Zhang, Pingping Tang
Silver-Mediated Oxidative Aliphatic C-H Trifluoromethylthiolation [Communication]

Silver-Mediated Oxidative Aliphatic C-H Trifluoromethylthiolation

The silver-mediated trifluoromethylthiolation of unactivated aliphatic C-H bonds is reported. The reaction is operationally simple, amenable to gram-scale synthesis, and can be employed for the late-stage trifluoromethylthiolation of complex small molecules.

Angew. Chem. Int. Ed. 2015, 54, No. 13, 4065-4069

Alexander W. Jones, Marie-Laure Louillat-Habermeyer, Frederic W. Patureau
Strained Dehydrogenative Ring Closure of Phenylcarbazoles [Communication]

Carboxylic Acids as Traceless Directing Groups for the Rhodium(III)-Catalyzed Decarboxylative C-H Arylation of Thiophenes

Who was in control? A rhodium(III)-catalyzed carboxylic acid directed decarboxylative C-H/C-H cross-coupling of benzoic acids with thiophenes has been developed. This method provides straightforward access to biaryl scaffolds with diverse substitution patterns, many of which previously required lengthy synthetic sequences.

Angew. Chem. Int. Ed. 2015, 54, No. 12, 3817-3821

Jidan Liu, Shaobo Zhuang, Qingwen Gui, Xiang Chen, Zhiyong Yang, Ze Tan
Copper-Mediated ortho-Nitration of Arene and Heteroarene C-H Bonds Assisted by an 8-Aminoquinoline Directing Group [Communication]

Krishnamoorthy Muralirajan, Radhakrishnan Haridharan, Sekar Prakash, Chien-Hong Cheng
Rhodium(III)-Catalyzed in situ Oxidizing Directing Group- Assisted C-H Bond Activation and Olefination: A Route to 2-Vinylanilines [Communication]

Irwan Iskandar Roslan, Jiulong Sun, Gaik-Khuan Chuah, Stephan Jaenicke
Cobalt(II)-Catalyzed Electrophilic Alkynylation of 1,3-Dicarbonyl Compounds To Form Polysubstituted Furans via π–π Activation [Communication]

Qizhi Ren, Yisong Guo, Matthew R. Mills, Alexander D. Ryabov, Terrence J. Collins
On the Iron(V) Reactivity of an Aggressive Tail-Fluorinated Tetraamido Macrocyclic Ligand (TAML) Activator [Full Paper]

On the Iron(V) Reactivity of an Aggressive Tail-Fluorinated Tetraamido Macrocyclic Ligand (TAML) Activator

The oxidation states of IV and V are achievable for electron-poor iron tetraamido macrocyclic ligand (TAML) activators. The corresponding oxidoiron(V) species demonstrates the highest reactivity reported so far for any TAML activator in the oxidation of thioanisole and C–H bond activations of ethylbenzene and cyclohexane.

Eur. J. Inorg. Chem. 2015, No. 08, 1445-1452

Cp*CoIII-Catalyzed C-H Activation of (Hetero)arenes: Expanding the Scope of Base-Metal-Catalyzed C-H Functionalizations

Directed activation: Cationic Cp*CoIII (Cp*=1,2,3,4,5-pentamethylcyclopentadienyl) complexes, either well-defined or in situ-generated, promote catalytic functionalization of arene C-H bonds with a variety of electrophilic reaction partners by directed C-H activation. These complexes not only emulate known reaction patterns of Cp*RhIII analogues, but also exhibit remarkable catalytic activity or unique reactivity. DG=Directing group.

ChemCatChem 2015, 7, No. 05, 732-734

Rhodium-Catalyzed Regioselective Direct C–H Amidation of 2,4-Diarylquinazoline with Sulfonyl Azides: An Example of Steric Hindrance Regulated Mono- and Diamidation Selectivity

Quinazoline acted as efficient directing group for the rhodium-catalyzed C–H amidation of 2,4-diarylquinazoline by using sulfonyl azides as the amine source. Satisfactory yields and excellent monoamidation selectivities were achieved with the assistance of meta substitutents.

Eur. J. Org. Chem. 2015, No. 08, 1735-1744

Jiayi Zhu, Yubo Kong, Feng Lin, Baoshuang Wang, Zhengwang Chen, Liangxian Liu
Copper-Catalyzed Direct Amination of 1,2,3-Triazole N-Oxides by C–H Activation and C–N Coupling [Full Paper]

Copper-Catalyzed Direct Amination of 1,2,3-Triazole N-Oxides by C–H Activation and C–N Coupling

A facile, efficient, and practical method for the copper-catalyzed direct C–H amination of 2-aryl-1,2,3-triazole N-oxides with various amines, including primary and secondary aliphatic and aromatic amines, has been developed. Furthermore, the targeted N+–O bond cleavage is observed during the reaction and, thus, an additional deoxygenation step is obviated.

Eur. J. Org. Chem. 2015, No. 07, 1507-1515

Dajian Zhu, Guoqiang Yang, Jian He, Ling Chu, Gang Chen, Wei Gong, Ke Chen, Martin D. Eastgate, Jin-Quan Yu
Ligand-Promoted ortho-C-H Amination with Pd Catalysts [Communication]

Ligand-Promoted ortho-C-H Amination with Pd Catalysts

Trimethoxylpyridine is an efficient ligand for promoting Pd-catalyzed ortho-C-H amination of both benzamides and triflyl-protected benzylamines. This finding provides guidance for the development of ligands that can improve or enable PdII-catalyzed Csp2-H activation reactions directed by weakly coordinating functional groups.

Angew. Chem. Int. Ed. 2015, 54, No. 08, 2497-2500

Weibo Yang, Shengqing Ye, Dewey Fanning, Timothy Coon, Yvonne Schmidt, Paul Krenitsky, Dean Stamos, Jin-Quan Yu
Orchestrated Triple C-H Activation Reactions Using Two Directing Groups: Rapid Assembly of Complex Pyrazoles [Communication]

Orchestrated Triple C-H Activation Reactions Using Two Directing Groups: Rapid Assembly of Complex Pyrazoles

Benzo[e]indazole derivatives are obtained by a sequential triple C-H activation directed by a pyrazole and an amide group. This cascade reaction demonstrates that the often problematic competing C-H activation pathways in the presence of multiple directing groups can be utilized to improve step economy in synthesis. Pyrazole as a relatively weak coordinating group is shown to direct Csp3-H activation.

Angew. Chem. Int. Ed. 2015, 54, No. 08, 2501-2504

Kai Chen, Shuo-Qing Zhang, Huai-Zhi Jiang, Jing-Wen Xu, Bing-Feng Shi
Practical Synthesis of anti-β-Hydroxy-α-Amino Acids by PdII-Catalyzed Sequential C(sp3)-H Functionalization [Full Paper]

Practical Synthesis of anti-β-Hydroxy-α-Amino Acids by PdII-Catalyzed Sequential C(sp3)-H Functionalization

An improved procedure for the stereoselective synthesis of anti-β-hydroxy-α-amino acids (anti-βhAAs) by palladium-catalyzed sequential C(sp3)-H functionalization directed by 8-aminoquinoline auxiliary is described (see scheme; Phth=phthaloyl). The synthetic potential of this protocol is further demonstrated by the synthesis of various β-branched α-AAs and β-mercapto-α-AAs.

Chem. Eur. J. 2015, 21, No. 08, 3264-3270

Noelia Casanova, Andrés Seoane, José L. Mascareñas, Moisés Gulías
Rhodium-Catalyzed (5+1) Annulations Between 2-Alkenylphenols and Allenes: A Practical Entry to 2,2-Disubstituted 2H-Chromenes [Communication]

Rhodium-Catalyzed (5+1) Annulations Between 2-Alkenylphenols and Allenes: A Practical Entry to 2,2-Disubstituted 2H-Chromenes

Skeleton crew: The synthesis of 2H-chromene skeletons was achieved by means of a rhodium(III)-catalyzed oxidative annulation of 2-alkenylphenols and allenes. This unconventional (5+1) process involves the cleavage of the terminal C-H bond of the alkenyl moiety and the participation of the allene as a one-carbon cycloaddition component.

Angew. Chem. Int. Ed. 2015, 54, No. 08, 2374-2377

Verónica Ortiz-de-Elguea, Nuria Sotomayor, Esther Lete
Two Consecutive Palladium(II)-Promoted C-H Alkenylation Reactions for the Synthesis of 3-Alkenylquinolones [Full Paper]

General Method for the Synthesis of Salicylic Acids from Phenols through Palladium-Catalyzed Silanol-Directed C-H Carboxylation

A strict director: The title reaction produced a wide range of salicylic acid derivatives with high efficiency and selectivity. The scope of this method was demonstrated by the carboxylation of estrone (see scheme; TBAF=tetrabutylammonium fluoride) and by the unsymmetrical bisfunctionalization of a phenolic compound through sequential C-H functionalization reactions.

Angew. Chem. Int. Ed. 2015, 54, No. 07, 2255-2259

Jonathan Hubrich, Thomas Himmler, Lars Rodefeld, Lutz Ackermann
Ruthenium(II)-Catalyzed C-H Arylation of Anilides with Boronic Acids, Borinic Acids and Potassium Trifluoroborates [Full Paper]

Guodong Zhang, Suyan Sun, Fan Yang, Qian Zhang, Jianxun Kang, Yusheng Wu, Yangjie Wu
Arylmethyl Chlorides: New Bifunctional Reagents for Palladium-Catalyzed ortho-Chlorination and Acylation of 2-Arylpyridines [Full Paper]

Youngmi Shin, Satyasheel Sharma, Neeraj Kumar Mishra, Sangil Han, Jihye Park, Hyunji Oh, Jimin Ha, Hyunwu Yoo, Young Hoon Jung, In Su Kim
Direct and Site-Selective Palladium-Catalyzed C-7 Acylation of Indolines with Aldehydes [Update]

Wajid Ali, Saroj K. Rout, Srimanta Guin, Anju Modi, Arghya Banerjee, Bhisma K. Patel
Copper-Catalyzed Cross Dehydrogenative Coupling of N,N-Disubstituted Formamides and Phenols: A Direct Access to Carbamates [Full Paper]

Radhakrishnan Haridharan, Krishnamoorthy Muralirajan, Chien-Hong Cheng
Rhodium(III)-Catalyzed ortho-Arylation of Anilides with Aryl Halides [Communication]

Biomimetic Oxidation with Fe-ZSM-5 and H2O2? Identification of an Active, Extra-Framework Binuclear Core and an FeIII-OOH Intermediate with Resonance-Enhanced Raman Spectroscopy

A pre-ferryl cat: Through in situ resonance-enhanced Raman spectroscopy, we identify an active, binuclear Fe-O(H)-Fe core and an FeIII-OOH intermediate in Fe-containing ZSM-5 following activation with H2O2. The pre-ferryl nature of this biomimetic intermediate may account for the unique ability of this solid catalyst to selectively oxidise methane to methanol under mild conditions.

ChemCatChem 2015, 7, No. 03, 434-440

Norbert Hoffmann
Combining Photoredox and Metal Catalysis [Highlight]

Combining Photoredox and Metal Catalysis

A photogenic pair: Photoredox catalysis with visible light and molecular oxygen as oxidant in combination with palladium catalysis enables highly efficient activation of C-H bonds. Mild photochemical reaction conditions generally facilitate the combination of different catalytic reactions.

ChemCatChem 2015, 7, No. 03, 393-394

Radical Chlorination with Hypervalent Iodine(III) Generated by Ligand Exchange: Revisiting Palladium(II)-Catalyzed Directed C-H Chlorination

Chlorination revisited: A radical chlorine species, generated by ligand exchange in hypervalent iodine(III) compounds, is demonstrated to promote Pd-catalyzed directed C-H chlorination. In this protocol, ammonium salts are used as chlorine sources.

Asian J. Org. Chem. 2015, 4, No. 02, 137-140

Silver-Mediated Cα(sp3)–H Functionalization of Primary Amines: An Oxidative C–N Coupling Strategy for the Synthesis of Two Different Types of 1,2,4,5-Tetrasubstituted Imidazoles

A new silver(I)-mediated Cα(sp3)–H bond functionalization of primary amines followed by an oxidative C–N cross-coupling reaction to form highly diverse 1,2,4,5-tetrasubstituted imidazoles has been demonstrated. This protocol provides a simple, highly efficient, and straightforward approach, which is promoted by a silver species, to give the products in good to excellent yields.

Eur. J. Org. Chem. 2015, No. 06, 1246-1256

Zhen Shu, Wei Li, Baiquan Wang
Pd/C-Catalyzed Synthesis of Isoquinolones through C-H Activation [Communication]

Pd/C-Catalyzed Synthesis of Isoquinolones through C-H Activation

Activation complete: The direct synthesis of isoquinolones from benzamides and alkynes through C-H activation is developed by using Pd/C as a heterogeneous catalyst. The Pd/C catalyst can be recycled three times without a significant decrease in the activity.

ChemCatChem 2015, 7, No. 04, 605-608

Palladium-Catalyzed Oxidative C-C Bond Cleavage of α-Hydroxyketones: Application to C-H Acylation of Azoarenes and Synthesis of a Liver(X) Receptor Agonist

Soul acyl-um: Palladium-catalyzed oxidative C-C cleavage of α-hydroxyketones and 2-aryl acetophenones in the presence of tert-butyl hydrogen peroxide (TBHP) and subsequent C-H acylation of azoarenes with the generated acyl moiety provides easy access to acyl azoarenes.

Asian J. Org. Chem. 2015, 4, No. 02, 154-163

Alexandre Vasseur, Caroline Laugel, Dominique Harakat, Jacques Muzart, Jean Le Bras
Ligand-Promoted Reactivity of Alkenes in Dehydrogenative Heck Reactions of Furans and Thiophenes [Short Communication]

Ligand-Promoted Reactivity of Alkenes in Dehydrogenative Heck Reactions of Furans and Thiophenes

The all around influence of 4,5-diazafluorenone as a ligand enables the dehydrogenative Heck reaction of furans and thiophenes with hindered alkenes. Very high stereoselectivity can be achieved. The ligand has an influence on C–H bond activation, insertion of the alkene, the stereodetermining step, and the aerobic regeneration of the catalyst.

Eur. J. Org. Chem. 2015, No. 05, 944-948

Yasutomo Segawa, Takehisa Maekawa, Kenichiro Itami
Synthesis of Extended π-Systems through C–H Activation [Review]

Synthesis of Extended π-Systems through C–H Activation

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 recent developments in this area directed toward new optoelectronic materials.

Angew. Chem. Int. Ed. 2015, 54, No. 01, 66-81

Rongwei Jin, Frederic W. Patureau
Metal-free Dehydrogenative Isoquinolone Synthesis [Highlight]

Metal-free Dehydrogenative Isoquinolone Synthesis

Versatile C-H bonds: We discuss Manna and Antonchick's metal-free isoquinolone synthesis through the dehydrogenative condensation of benzamides with alkynes and what it means for the fields of C-H functionalization and organic synthesis. DG=Directing group, E=electrophile.

ChemCatChem 2015, 7, No. 02, 223-225

Malek Nechab, Shovan Mondal, Michèle P. Bertrand
1,n-Hydrogen-Atom Transfer (HAT) Reactions in Which n≠5: An Updated Inventory [Review]

1,n-Hydrogen-Atom Transfer (HAT) Reactions in Which n≠5: An Updated Inventory

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.

Chem. Eur. J. 2014, 20, No. 49, 16034-16059

Matthijs Ruitenbeek, Bert M. Weckhuysen
A Radical Twist to the Versatile Behavior of Iron in Selective Methane Activation [Highlight]

A Radical Twist to the Versatile Behavior of Iron in Selective Methane Activation

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.

Angew. Chem. Int. Ed. 2014, 53, No. 42, 11137-11139

Niles J. Gunsalus, Michael M. Konnick, Brian G. Hashiguchi, Roy A. Periana
Discrete Molecular Catalysts for Methane Functionalization [Review]

Rowan D. Young
Characterisation of Alkane σ-Complexes [Minireview]

Characterisation of Alkane σ-Complexes

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.

Chem. Eur. J. 2014, 20, No. 40, 12704-12718

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. 2014, 53, No. 36, 9426-9428

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. 2014, No. 27, 5863-5883

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

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

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

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

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

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

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