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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

Xinkun Ren, Jake A. Yorke, Emily Taylor, Ting Zhang, Weihong Zhou, Luet Lok Wong
Drug Oxidation by Cytochrome P450BM3: Metabolite Synthesis and Discovering New P450 Reaction Types [Full Paper]

Drug Oxidation by Cytochrome P450BM3: Metabolite Synthesis and Discovering New P450 Reaction Types

Library binder: The scalable oxidation of a panel of drug molecules by a library of P450BM3 mutants generated human metabolites on a preparative scale and led to the discovery of new P450 reaction types, indicating that the library may be a good source of late-stage C-H activation catalysts.

Chem. Eur. J., August 27, 2015, DOI: 10.1002/chem.201502020

Shu-Tao Mei, Kun Jiang, Nan-Jin Wang, Li Shuai, Yi Yuan, Ye Wei
Rhodium-Catalyzed Direct C–H Vinylation of Arenes To Access Styrenes with Vinyl Acetate as a Vinyl Source [Short Communication]

Rhodium-Catalyzed Direct C–H Vinylation of Arenes To Access Styrenes with Vinyl Acetate as a Vinyl Source

A variety of styrenes are prepared through RhIII-catalyzed direct aryl C–H vinylation with commercially available and inexpensive vinyl acetate as the vinyl source. This method enables various aromatics including N-sulfonyl ketimines, pyridines, azoles, and amides to be vinylated in moderate to good yields.

Eur. J. Org. Chem., August 26, 2015, DOI: 10.1002/ejoc.201500945

Bing Zhou, Zhaoqiang Chen, Yaxi Yang, Wen Ai, Huanyu Tang, Yunxiang Wu, Weiliang Zhu, Yuanchao Li
Redox-Neutral Rhodium-Catalyzed C-H Functionalization of Arylamine N-Oxides with Diazo Compounds: Primary C(sp3)- H/C(sp2)-H Activation and Oxygen-Atom Transfer [Communication]

Redox-Neutral Rhodium-Catalyzed C-H Functionalization of Arylamine N-Oxides with Diazo Compounds: Primary C(sp3)- H/C(sp2)-H Activation and Oxygen-Atom Transfer

Untapped reactivity: The title reaction affords 1H-benzo[g]indolines under mild reaction conditions and external oxidants are not required. The only by-products are dinitrogen and water. This reaction represents the first example of dual functionalization of an unactivated primary C(sp3)-H and C(sp2)-H bond with diazocarbonyl compounds. Moreover, a method to access various aminomandelic acid derivatives by an O-atom-transfer strategy is described.

Angew. Chem. Int. Ed., August 26, 2015, DOI: 10.1002/anie.201505302

Directing/Protecting-Group-Free Synthesis of Tetraaryl-Substituted Pyrazoles through Four Direct Arylations on an Unsubstituted Pyrazole Scaffold

Free from direction: A new approach has been developed for the preparation of tetraaryl-substituted pyrazoles without the need for directing or protecting groups. This was achieved by means of four transition-metal-catalyzed arylations. Various pyrazoles with four different aryl rings were obtained from an unsubstituted pyrazole. Two aryl-substituted pyrazoles showed intense violet fluorescence, high quantum yields (Φf=0.68, 0.64), and large Stokes shifts (19000, 15200 cm−1).

Chem. Eur. J., August 21, 2015, DOI: 10.1002/chem.201502399

Radim Hrdina, Fabian M. Metz, Marta Larrosa, Jan-Philipp Berndt, Yevgeniya Y. Zhygadlo, Sabine Becker, Jonathan Becker
Intramolecular C–H Amination Reaction Provides Direct Access to 1,2-Disubstituted Diamondoids [Full Paper]

Intramolecular C–H Amination Reaction Provides Direct Access to 1,2-Disubstituted Diamondoids

Intramolecular dirhodium-acetate-catalyzed (1 mol-%) nitrene insertion reactions provide direct access to 1,2-disubstituted diamondoids. This approach was applied to the synthesis of Vildagliptin® (DPP-4 inhibitor) analogues.

Eur. J. Org. Chem., August 20, 2015, DOI: 10.1002/ejoc.201500691

Xiaoge Yang, Zhuqing Liu, Chenglin Sun, Jiping Chen, Zhengkun Yu
Palladium-Catalyzed Oxidative Cross-Coupling of α-Cyanoketene Dithioacetals with Olefins [Full Paper]

Palladium-Catalyzed Oxidative Cross-Coupling of α-Cyanoketene Dithioacetals with Olefins

Internal olefinic C-H olefination: Palladium-catalyzed oxidative cross-coupling of α-cyanoketene dithioacetals with various olefins has been efficiently realized with air or AgOAc as the terminal oxidant in dioxane/HOAc/DMSO (9:3:1 v/v/v) under mild conditions. A catalytic amount of benzoquinone (BQ) is found to remarkably promote the reactions of α-cyanoketene dithioacetals with unactivated cyclic and linear internal olefins.

Chem. Eur. J., August 19, 2015, DOI: 10.1002/chem.201502280

Rajendran Manikandan, Padmaja Madasamy, Masilamani Jeganmohan
Ruthenium-Catalyzed Oxidant-Free Allylation of Aromatic Ketoximes with Allylic Acetates at Room Temperature [Communication]

Ruthenium-Catalyzed Oxidant-Free Allylation of Aromatic Ketoximes with Allylic Acetates at Room Temperature

Substituted aromatic ketoximes reacted efficiently with allylic acetates in the presence of {[RuCl2(p-cymene)]2} and AgSbF6 in 1,2-dichloroethane at ambient temperature, providing ortho-allyl aromatic ketoximes in a highly regioselective manner without an oxidant. In the reaction, the acetate group of allyl acetate acts as a base to activate the C-H bond of aromatics. Later, ortho-allyl aromatic ketoximes were converted into ortho-allyl aromatic ketones in the presence of HCl.

Chem. Eur. J., August 19, 2015, DOI: 10.1002/chem.201502284

Shubhankar Kumar Bose, Andrea Deißenberger, Antonius Eichhorn, Patrick G. Steel, Zhenyang Lin, Todd B. Marder
Zinc-Catalyzed Dual C–X and C–H Borylation of Aryl Halides [Communication]

Zinc-Catalyzed Dual C–X and C–H Borylation of Aryl Halides

Two B or not two B: A novel catalytic system based on a ZnII-dtbpy precursor was developed for the preparation of 1,2-diborylarenes. This method represents a new type of catalytic process for diborylation of aryl halides via both C-X and C-H activation.

Angew. Chem. Int. Ed., August 18, 2015, DOI: 10.1002/anie.201505603

Christopher J. Teskey, Andrew Y. W. Lui, Michael F. Greaney
Ruthenium-Catalyzed meta-Selective C-H Bromination [Communication]

Ruthenium-Catalyzed meta-Selective C-H Bromination

Taking position: 2-Phenylpyridines undergo meta-selective bromination using tetrabutylammonium tribromide under ruthenium catalysis, thus affording products that are highly predisposed to further derivatization. The bromination can be combined with arylation and alkenylation chemistry to access meta-arylated and meta-alkenylated products, respectively, in a one-pot operation.

Angew. Chem. Int. Ed., August 18, 2015, DOI: 10.1002/anie.201504390

Eric M. Phillips, Tehetena Mesganaw, Ashay Patel, Simon Duttwyler, Brandon Q. Mercado, Kendall N. Houk, Jonathan A. Ellman
Synthesis of ent-Ketorfanol via a C–H Alkenylation/Torquoselective 6π Electrocyclization Cascade [Communication]

Synthesis of ent-Ketorfanol via a C–H Alkenylation/Torquoselective 6π Electrocyclization Cascade

The asymmetric synthesis of ent-ketorfanol from simple and commercially available precursors is reported. A RhI-catalyzed intramolecular C-H alkenylation/torquoselective 6π electrocyclization cascade provides a fused bicyclic 1,2-dihydropyridine as a key intermediate. The ketone functionality and final ring are introduced in a single step through a redox-neutral acid-catalyzed rearrangement of a vicinal diol followed by intramolecular Friedel–Crafts alkylation.

Angew. Chem. Int. Ed., August 17, 2015, DOI: 10.1002/anie.201505604

Dehydrogenative Carbon–Carbon Bond Formation Using Alkynoxy Moieties as Hydrogen-Accepting Directing Groups

Alkyne into alkene: A palladium catalyst enables dehydrogenative C-C bond-forming reactions between alkynyl aryl ethers and alkenes or heteroarenes. The presence of the alkynoxy group is key for these transformations as it acts as a directing group for the site-selective cleavage of two C-H bonds as well as an acceptor for the released hydrogen.

Angew. Chem. Int. Ed., August 14, 2015, DOI: 10.1002/anie.201505789

Emilien Demory, Karthik Devaraj, Andreas Orthaber, Paul J. Gates, Lukasz T. Pilarski
Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through C-H Activation and Orthogonal Reactivity [Communication]

Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through C-H Activation and Orthogonal Reactivity

Ready for a complete makeover: As building blocks for arylation, (pinacolato)boryl ortho-silyl (hetero)aryl triflates (see structure; X=C, N; FG=functional group) showed unique versatility by reacting chemoselectively as boronates or (hetero)arynes in a broad range of transformations. This approach offers valuable possibilities for the functionalization of both aryne precursors and aryl boronates without the use of specialized protecting groups.

Angew. Chem. Int. Ed., August 13, 2015, DOI: 10.1002/anie.201503152

Chiral γ-Lactams by Enantioselective Palladium(0)-Catalyzed Cyclopropane Functionalizations

Bulk up: An enantioselective C-H functionalization strategy is used to access cyclopropane-fused γ-lactams from readily accessible chloroacetamide substrates. A bulky Taddol phosphonite ligand in combination with adamantane-1-carboxylic acid as a cocatalyst provides the γ-lactams in excellent yields and enantioselectivities.

Angew. Chem. Int. Ed., August 12, 2015, DOI: 10.1002/anie.201505916

Diversity-Oriented Synthesis through Rh-Catalyzed Selective Transformations of a Novel Multirole Directing Group

Chemical multitasking: A novel N-N bond containing a multirole directing group is developed, which enables the synthesis of four different products selectively from the same starting material through RhIII catalysis. Key features include ready availability, multiple reactive sites, high redox selectivity and controllability, and multifarious transformations toward important scaffolds and structural diversification. Phth=phthaloyl; DCE=1,2-dichloroethane.

ChemCatChem, August 10, 2015, DOI: 10.1002/cctc.201500410

Solvent-Free Ruthenium(II)-Catalyzed C–H Activation: Synthesis of Alkenylarylpyrazole Derivatives

The alkenylation of arylpyrazoles and phenyloxazolines by using Ru(MesCO2)2(p-cymene) (Mes = mesityl) as a catalyst and Cu(OAc)2 as an oxidant is reported. Mono- and dialkenylated products can be obtained by controlling the amount of alkene used. The reaction is site selective and takes place exclusively at the ortho position of the heteroaryl moiety.

Eur. J. Org. Chem., August 6, 2015, DOI: 10.1002/ejoc.201500634

Brian N. Laforteza, Kelvin S. L. Chan, Jin-Quan Yu
Enantioselective ortho-C-H Cross-Coupling of Diarylmethylamines with Organoborons [Communication]

Enantioselective ortho-C-H Cross-Coupling of Diarylmethylamines with Organoborons

Amine-directed: A new enantioselective ortho-C-H cross-coupling reaction between nosyl-protected diarylmethylamines and arylboronic acid pinacol esters has been achieved with chiral mono-N-protected amino acids (MPAA) as chiral ligands. This reaction also demonstrates the feasibility of using a common protecting group to direct C-H activation of amines for the first time.

Angew. Chem. Int. Ed., August 4, 2015, DOI: 10.1002/anie.201505204

Francesco Ferretti, Mohamed A. EL-Atawy, Stefania Muto, Mohamed Hagar, Emma Gallo, Fabio Ragaini
Synthesis of Indoles by Palladium-Catalyzed Reductive Cyclization of β-Nitrostyrenes with Carbon Monoxide as the Reductant [Short Communication]

Synthesis of Indoles by Palladium-Catalyzed Reductive Cyclization of β-Nitrostyrenes with Carbon Monoxide as the Reductant

Indoles and azaindoles can be obtained by reductive cyclization of β-nitrostyrenes, which can be easily obtained in most cases from cheap nitroalkanes and aromatic aldehydes. The method is effective for the synthesis of both 2- and 3-substituted indoles; Phen = 1,10-phenanthroline.

Eur. J. Org. Chem., August 3, 2015, DOI: 10.1002/ejoc.201500933

Rishikesh Narayan, Kiran Matcha, Andrey P. Antonchick
Metal-Free Oxidative C-C Bond Formation through C-H Bond Functionalization [Minireview]

Metal-Free Oxidative C-C Bond Formation through C-H Bond Functionalization

Who needs metals anyway? This Minireview covers the rapidly growing area of metal-free oxidative C-C bond formation through direct C-H bond functionalization. A selection of recent important developments in this area is presented along with discussions of their reaction mechanisms.

Chem. Eur. J., August 3, 2015, DOI: 10.1002/chem.201502005

Metal-Free Oxidative C–H Amidation of N,N'-Diarylureas with PhI(OAc)2: Synthesis of Benzimidazol-2-one Derivatives

A simple and practical metal-free oxidative C–H amidation of N,N'-diarylureas has been developed. This protocol uses readily available N,N'-diarylureas as starting materials and inexpensive PhI(OAc)2 as an oxidant without the need for a catalyst, ligand, or the exclusion of air. The method has wide functional group tolerance and provides a new strategy to synthesize N-heterocycles.

Eur. J. Org. Chem., July 31, 2015, DOI: 10.1002/ejoc.201500726

Puneet K. Gupta, Nisha Yadav, Subodh Jaiswal, Mohd. Asad, Ruchir Kant, Kanchan Hajela
Palladium-Catalyzed Synthesis of Phenanthridine/Benzoxazine-Fused Quinazolinones by Intramolecular C-H Bond Activation [Communication]

Palladium-Catalyzed Synthesis of Phenanthridine/Benzoxazine-Fused Quinazolinones by Intramolecular C-H Bond Activation

A short fuse: A highly efficient synthesis of phenanthridine/benzoxazine-fused quinazolinones by ligand-free palladium-catalyzed intramolecular C-H bond activation under mild conditions has been developed. The C-C coupling provides the corresponding N-fused polycyclic heterocycles in good to excellent yields.

Chem. Eur. J., July 31, 2015, DOI: 10.1002/chem.201501591

Yinan Zhang, Qing Ye, Xiachang Wang, Qing-Bai She, Jon S. Thorson
A Divergent Enantioselective Strategy for the Synthesis of Griseusins [Communication]

A Divergent Enantioselective Strategy for the Synthesis of Griseusins

The total synthesis of three naturally occurring and two non-natural griseusins 1 is achieved by a strategy including a key hydroxy-directed C-H olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. It was found that the stereochemistry and functionalization of the tetrahydro-spiropyran ring has a high impact on bioactivity.

Angew. Chem. Int. Ed., July 31, 2015, DOI: 10.1002/anie.201505022

Shashikant U. Dighe, Sushobhan Mukhopadhyay, Shivalinga Kolle, Sanjeev Kanojiya, Sanjay Batra
Synthesis of 3,4,5-Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2-Mediated Domino Reaction [Communication]

Synthesis of 3,4,5-Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2-Mediated Domino Reaction

An efficient synthesis of highly substituted isoxazoles from the reaction of allyl acetates with NaNO2 by using I2 under oxidative conditions is demonstrated. The reactions proceed through an I2-assisted activation of the C-H bond α to the nitro group, nucleophilic addition, and subsequent [3+2] cycloaddition. DMF=N,N-dimethylformamide, DMSO=dimethylsulfoxide.

Angew. Chem. Int. Ed., July 23, 2015, DOI: 10.1002/anie.201504529

Ju Hyun Kim, Tobias Gensch, Dongbing Zhao, Linda Stegemann, Cristian A. Strassert, Frank Glorius
RhIII-Catalyzed C-H Activation with Pyridotriazoles: Direct Access to Fluorophores for Metal-Ion Detection [Communication]

RhIII-Catalyzed C-H Activation with Pyridotriazoles: Direct Access to Fluorophores for Metal-Ion Detection

Form(ation) follows function: The first C-H bond activation with pyridotriazoles as a coupling partner is made possible by using a RhIII catalyst. The pyridotriazoles serve as new carbene precursors in C-H activation allowing direct access to fluorescent scaffolds bearing a pyridine-type ligating group. These fluorophores can be applied as dual sensors for colorimetric sensing of Cu2+ ions and fluorescence sensing for Zn2+ ions.

Angew. Chem. Int. Ed., July 23, 2015, DOI: 10.1002/anie.201504757

Hao Yan, Haolong Wang, Xincheng Li, Xiaoyi Xin, Chunxiang Wang, Boshun Wan
Rhodium-Catalyzed C-H Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3-Diaryl-Substituted Indoles [Communication]

Rhodium-Catalyzed C-H Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3-Diaryl-Substituted Indoles

They know their place: Unsymmetrically 2,3-diaryl-substituted N-unprotected indoles were synthesized by the rhodium(III)-catalyzed annulation of nitrones with symmetrical diaryl alkynes. Exclusive regioselectivity was observed, as one of the two aryl substituents on the resulting indole ring is derived from the C-aryl ring of the nitrone, and the other from the alkyne.

Angew. Chem. Int. Ed. 2015, 54, No. 36, 10613-10617

Céline Taglang, Luis Miguel Martínez-Prieto, Iker del Rosal, Laurent Maron, Romuald Poteau, Karine Philippot, Bruno Chaudret, Serge Perato, Anaïs Sam Lone, Céline Puente, Christophe Dugave, Bernard Rousseau, Grégory Pieters
Enantiospecific C-H Activation Using Ruthenium Nanocatalysts [Communication]

Enantiospecific C-H Activation Using Ruthenium Nanocatalysts

Various compounds, such as amines, amino acids, or peptides, can undergo enantiospecific C-H activation/deuteration in the presence of ruthenium nanocatalysts under mild conditions. Theoretical studies revealed a four-membered dimetallacycle as the key intermediate and suggested that the collective motion of surface species can facilitate the C-H activation step by modulating the local electronic structure.

Angew. Chem. Int. Ed. 2015, 54, No. 36, 10474-10477

Facile, One-Pot, and Gram-Scale Synthesis of 3,4,5-Triiodoanisole through a C–H Iodination/ipso-Iododecarboxylation Strategy: Potential Application towards 3,4,5-Trisubstituted Anisoles

The facile and efficient synthesis of hitherto unknown 3,4,5-triiodoanisole in a tandem one-pot C–H iodination/ipso-iododecarboxylation reaction that is catalytic, scalable, easy to work up, and easy to purify is disclosed. Potential application of the target compound as a precursor for novel site-selective metal–iodine exchange and Suzuki–Miyaura cross-coupling reactions are demonstrated.

Eur. J. Org. Chem. 2015, No. 25, 5501-5508

Lutz F. Tietze, Bernd Waldecker, Dhandapani Ganapathy, Christoph Eichhorst, Thomas Lenzer, Kawon Oum, Sven O. Reichmann, Dietmar Stalke
Four- and Sixfold Tandem-Domino Reactions Leading to Dimeric Tetrasubstituted Alkenes Suitable as Molecular Switches [Communication]

Four- and Sixfold Tandem-Domino Reactions Leading to Dimeric Tetrasubstituted Alkenes Suitable as Molecular Switches

Highly efficient palladium-catalyzed fourfold tandem-domino reactions consisting of two carbopalladation and two C-H-activation steps were developed for the synthesis of two types of tetrasubstituted alkenes with intrinsic helical chirality. 20 different substrates were prepared with yields of up to 97 %. Photophysical investigations revealed light-induced switching properties of the products.

Angew. Chem. Int. Ed. 2015, 54, No. 35, 10317-10321

Acylation of (Hetero)Arenes through C-H Activation with Aroyl Surrogates

In splendid acylation: The major achievements in the acylation of arenes and heteroarenes by C-H activation with aroyl groups are summarized and discussed, based on the aroyl sources employed. In light of these achievements and their mechanistic studies, possible problems for carbonylative diaryl ketone synthesis by C-H activation are also discussed (see scheme; DG=directing group).

Chem. Eur. J. 2015, 21, No. 35, 12252-12265

David J. Burns, Daniel Best, Martin D. Wieczysty, Hon Wai Lam
All-Carbon [3+3] Oxidative Annulations of 1,3-Enynes by Rhodium(III)-Catalyzed C-H Functionalization and 1,4-Migration [Communication]

All-Carbon [3+3] Oxidative Annulations of 1,3-Enynes by Rhodium(III)-Catalyzed C-H Functionalization and 1,4-Migration

All for one and 1,4-all(yl): 1,3-Enynes containing allylic hydrogens cis to the alkyne act as three-carbon components in rhodium(III)-catalyzed, all-carbon [3+3] oxidative annulations to produce spirodialins. The proposed mechanism of these reactions involves the alkenyl-to-allyl 1,4-rhodium(III) migration.

Angew. Chem. Int. Ed. 2015, 54, No. 34, 9958-9962

Yudai Suzuki, Bo Sun, Ken Sakata, Tatsuhiko Yoshino, Shigeki Matsunaga, Motomu Kanai
Dehydrative Direct C-H Allylation with Allylic Alcohols under [Cp*CoIII] Catalysis [Communication]

Dehydrative Direct C-H Allylation with Allylic Alcohols under [Cp*CoIII] Catalysis

The unique reactivity of [Cp*CoIII] versus [Cp*RhIII] is showcased in the direct dehydrative C-H allylation with non-activated allyl alcohols. Cationic [Cp*CoIII] gave C2-allylated indoles, pyrrole, and phenyl-pyrazole in good yields, while the analogous [Cp*RhIII] catalysts were not effective. The high γ-selectivity and C2-selectivity result from directing-group-assisted C-H metalation, insertion of a C-C double bond, and subsequent β-hydroxide elimination. Cp*=C5Me5.

Angew. Chem. Int. Ed. 2015, 54, No. 34, 9944-9947

Lin-Bao Zhang, Xin-Qi Hao, Zhan-Jiang Liu, Xin-Xiang Zheng, Shou-Kun Zhang, Jun-Long Niu, Mao-Ping Song
Cobalt(II)-Catalyzed Csp2-H Alkynylation/Annulation with Terminal Alkynes: Selective Access to 3-Methyleneisoindolin-1-one [Communication]

Cobalt(II)-Catalyzed Csp2-H Alkynylation/Annulation with Terminal Alkynes: Selective Access to 3-Methyleneisoindolin-1-one

Directing group and Co: The title reaction proceeds in the presence of an N,O-bidentate directing group. This method is characterized by wide substrate scope and cheap cobalt catalysts, and offers a new approach to 3-methyleneisoindolin-1-one, which can be converted into an oxadiazine salt in one step. Moreover, the directing group can be removed in three steps. CAN=ceric ammonium nitrate.

Angew. Chem. Int. Ed. 2015, 54, No. 34, 10012-10015

Peng Sun, Youzhi Wu, Tie Yang, Xiaoming Wu, Jinyi Xu, Aijun Lin, Hequan Yao
Synthesis of Heterocycle-fused Pyridine N-Oxides from Oximes and Diazo Compounds via RhIII-Catalyzed C-H Activation and Annulation [Communication]

Unprecedented Transformation of a Directing Group Generated In Situ and Its Application in the One-Pot Synthesis of 2-Alkenyl Benzonitriles

Directly functional! Cyanation and olefination was accomplished in one pot from benzoyl azides through an unprecedented directing group transformation. The method generates benzonitriles and can be used for the synthesis of 2-alkenylated benzonitrile derivatives (see scheme).

Chem. Eur. J. 2015, 21, No. 33, 11807-11812

Masashi Shigenobu, Kazuhiro Takenaka, Hiroaki Sasai
Palladium-Catalyzed Direct C-H Arylation of Isoxazoles at the 5-Position [Communication]

Palladium-Catalyzed Direct C-H Arylation of Isoxazoles at the 5-Position

Knock your 'sox' off: A palladium catalyst promotes the cross-coupling of isoxazoles with aryl iodides through the selective C-H bond activation at the 5-position of the heteroaromatic compound. The use of 1,2-bis(diphenylphosphino)benzene as the ligand and silver fluoride as the activator was found to be crucial for this direct arylation. FG=functional group.

Angew. Chem. Int. Ed. 2015, 54, No. 33, 9572-9576

Yu-ki Tahara, Mamoru Ito, Kyalo Stephen Kanyiva, Takanori Shibata
Total Synthesis of cis-Clavicipitic Acid from Asparagine via Ir-Catalyzed C-H bond Activation as a Key Step [Communication]

Total Synthesis of cis-Clavicipitic Acid from Asparagine via Ir-Catalyzed C-H bond Activation as a Key Step

4-Substituted tryptophan derivatives and the total synthesis of cis-clavicipitic acid were achieved in reactions in which Ir-catalyzed C-H bond activation was a key step. The starting material for these reactions is asparagine, which is a cheap natural amino acid. The reductive amination step from the 4-substituted tryptophan derivative gave cis-clavicipitic acid with perfect diastereoselectivity (cbz=carbobenzyloxy).

Chem. Eur. J. 2015, 21, No. 32, 11340-11343

Rhodium(III)-Catalyzed Activation of Csp3-H Bonds and Subsequent Intermolecular Amidation at Room Temperature

Giving direction: The title reaction leads to the successful functionalization of unreactive Csp3-H bonds in the presence of directing groups (DGs). A rhodacycle having a SbF6 counterion was isolated and is proposed to be a plausible intermediate.

Angew. Chem. Int. Ed. 2015, 54, No. 32, 9404-9408

Shuai Mao, Xue-Qing Zhu, Ya-Ru Gao, Dong-Dong Guo, Yong-Qiang Wang
Silver-Catalyzed Coupling of Two Csp3-H Groups and One-Pot Synthesis of Tetrasubstituted Furans, Thiophenes, and Pyrroles [Communication]

Silver-Catalyzed Coupling of Two Csp3-H Groups and One-Pot Synthesis of Tetrasubstituted Furans, Thiophenes, and Pyrroles

A three-ring circus: A silver-catalyzed coupling of two Csp3-H groups followed by cyclization has been developed. The approach provides a general and efficient access to tetrasubstituted furans, thiophenes, and pyrroles from easily accessible benzyl ketone derivatives in a one-pot reaction process.

Chem. Eur. J. 2015, 21, No. 32, 11335-11339

Selectfluor–Bu4NI-Mediated C(sp3)–H Oxidation in Aqueous Media: Synthesis of Δ2-Isoxazolines from Oximes

The title reaction involves Selectfluor–Bu4NI-mediated C–O bond formation in aqueous media under metal-free conditions. A variety of Δ2-isoxazolines are directly synthesized from oximes by remote intramolecular functionalization of C(sp3)–H bonds.

Eur. J. Org. Chem. 2015, No. 23, 5084-5088

Irina E. Iagafarova, Daria V. Vorobyeva, Alexander S. Peregudov, Sergey N. Osipov
CF3-Carbenoid C–H Functionalization of (Hetero)arenes under Chelation-Controlled RhIII Catalysis [Full Paper]

CF3-Carbenoid C–H Functionalization of (Hetero)arenes under Chelation-Controlled RhIII Catalysis

An efficient method for the CF3-carbenoid C–H functionalization of benzenes and indoles using readily available methyl 3,3,3-trifluoro-2-diazopropionate under chelation-controlled RhIII catalysis has been developed. The reaction proceeds with high regioselectivity and allows the simultaneous introduction of CF3 and COOMe groups into the 2-position of directing-group-containing benzenes and indoles.

Eur. J. Org. Chem. 2015, No. 22, 4950-4955

Jian-Gang Huang, Ying Guo, Yu-Dan Li, Hong-Wei Liu, Dao-Hua Liao, Ya-Fei Ji
Undecorated Cu(OAc)2-Catalyzed C(sp3)–C(sp3) Bond Formation through para-Hydroxy Group Triggered Remote Benzylic C(sp3)–H Bond Functionalization [Short Communication]

Undecorated Cu(OAc)2-Catalyzed C(sp3)–C(sp3) Bond Formation through para-Hydroxy Group Triggered Remote Benzylic C(sp3)–H Bond Functionalization

The Cu(OAc)2-catalyzed para-hydroxy group triggered oxidative coupling of 2,6-disubstituted-4-cresols with fluorinated β-ketone esters or malonates leading to benzylic C(sp3)–C(sp3) bond formation is described with ambient air as the terminal oxidant. Highly functionalized 3-phenylpropanoate derivatives containing fluorinated quaternary carbon-like centers are constructed in an ecofriendly manner.

Eur. J. Org. Chem. 2015, No. 24, 5334-5338

Metal-Free Dehydrogenative Diels–Alder Reactions of 2-Methyl-3-Alkylindoles with Dienophiles: Rapid Access to Tetrahydrocarbazoles, Carbazoles, and Heteroacenes

Setting a trap: Described is a strategy for in situ generation of indole-based ortho-quinodimethanes (oQDMs) from the title indoles through either a DDQ- or BQ-mediated dehydrogenative process. These oQDMs are trapped by electron-deficient olefins, thus providing facile access to tetrahydrocarbazoles, carbazoles, and hetereoacenes. BQ=benzoquinone, DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

Angew. Chem. Int. Ed. 2015, 54, No. 31, 9092-9096

RhIII-Catalyzed C(sp3)-H Bond Activation by an External Base Metalation/Deprotonation Mechanism: A Theoretical Study

Rounding the cycle: A theoretical investigation shows that the C(sp3)-H bond activation of methylquinoline with Cu(OAc)2 or free acetate occurs by an external base concerted metalation/deprotonation (CMD) mechanism (see scheme: RDS=rate-determining step). The C-H activation is followed by cationic alkyne insertion.

Chem. Eur. J. 2015, 21, No. 31, 11158-11164

Johannes Kaschel, Daniel B. Werz
Ethynyl Benziodoxolone (EBX): Installing Alkynes the Reversed Way [Highlight]

Ethynyl Benziodoxolone (EBX): Installing Alkynes the Reversed Way

Umpolung of alkynes: The hypervalent iodine reagent EBX (ethynyl benziodoxolone) can be employed for the electrophilic introduction of alkynes. Aside from its unusual reactivity, mild reaction conditions and a high tolerance towards various functional groups are remarkable features of this stable reagent and its reactions.

Angew. Chem. Int. Ed. 2015, 54, No. 31, 8876-8878

Gui-Juan Cheng, Ping Chen, Tian-Yu Sun, Xinhao Zhang, Jin-Quan Yu, Yun-Dong Wu
A Combined IM-MS/DFT Study on [Pd(MPAA)]-Catalyzed Enantioselective C-H Activation: Relay of Chirality through a Rigid Framework [Full Paper]

A Combined IM-MS/DFT Study on [Pd(MPAA)]-Catalyzed Enantioselective C-H Activation: Relay of Chirality through a Rigid Framework

Relay of chirality: A combined ion-mobility mass spectrometry (IM-MS) and DFT study has been carried out to investigate chiral Pd/monoprotected amino acid (MPAA)-enabled direct asymmetric C-H activation reactions. The enantioselectivity originates from the rigid square-planar Pd coordination in the C-H activation transition state: Bidentate MPAA and substrate coordination (see figure: DG=directing group).

Chem. Eur. J. 2015, 21, No. 31, 11180-11188

Wei Zheng, Bei-Bei Wang, Cheng-Hui Li, Jing-Xuan Zhang, Cheng-Zhang Wan, Jia-Hao Huang, Jian Liu, Zhen Shen, Xiao-Zeng You
Asymmetric Donor–π-Acceptor-Type Benzo-Fused Aza-BODIPYs: Facile Synthesis and Colorimetric Properties [Communication]

Asymmetric Donor–π-Acceptor-Type Benzo-Fused Aza-BODIPYs: Facile Synthesis and Colorimetric Properties

Dyes at the crossroads: By using tBuOK/DMF as base to ionize the phthalonitrile, we have developed a facile method to synthesize asymmetric donor–π-acceptor-type benzo-fused aza-BODIPY complexes. The newly prepared aza-BODIPYs exhibit novel colorimetric properties which could be attributed to the fracturing and restoration of the B-N bond.

Angew. Chem. Int. Ed. 2015, 54, No. 31, 9070-9074

Nickel-Catalyzed C-O/C-H Cross-Coupling Reactions for C-C Bond Formation

Halides not required: Nickel-catalyzed C-O/C-H cross-couplings for the construction of C-C bonds have recently been disclosed. By carefully optimizing the nickel catalyst, new C-C bond-forming reactions were developed, and even quaternary stereogenic centers are now accessible in high yields from readily available phenoxide derivatives and hydrocarbons.

Angew. Chem. Int. Ed. 2015, 54, No. 30, 8600-8602

Robin B. Bedford, Steven J. Durrant, Michelle Montgomery
Catalyst-Switchable Regiocontrol in the Direct Arylation of Remote C-H Groups in Pyrazolo[1,5-a]pyrimidines [Communication]

Catalyst-Switchable Regiocontrol in the Direct Arylation of Remote C-H Groups in Pyrazolo[1,5-a]pyrimidines

Remote control: Switching the regioselectivity of C-H arylation between remote sites on pyrazolo[1,5-a]pyrimidine can be achieved by tuning the structure of the catalyst. The control appears to be due to a change in mechanistic pathways between electrophilic palladation and base-assisted deprotonation.

Angew. Chem. Int. Ed. 2015, 54, No. 30, 8787-8790

Ai-Hua Zhou, Fei Pan, Chunyin Zhu, Long-Wu Ye
Recent Progress towards Transition-Metal-Catalyzed Synthesis of Fluorenes [Minireview]

Recent Progress towards Transition-Metal-Catalyzed Synthesis of Fluorenes

Fluorene structures are commonly encountered in materials science, pharmaceutical chemistry, and organic synthesis. This Minireview summarizes how transition metal catalysis has become the prevalent strategy for the synthesis of fluorenes, as highlighted by examples from throughout the last decade.

Chem. Eur. J. 2015, 21, No. 29, 10278-10288

Palladium(II)-Catalyzed meta-C-H Olefination: Constructing Multisubstituted Arenes through Homo-Diolefination and Sequential Hetero-Diolefination

Jockeying for position: Reported herein is the palladium-catalyzed synthesis of mono- and divinylbenzenes by meta-C-H olefination of benzyl sulfones. Successful sequential olefinations in a position-selective manner provided a novel route for the synthesis of hetero-dialkenylated products, which are difficult to access using conventional methods. DG=directing group.

Angew. Chem. Int. Ed. 2015, 54, No. 29, 8515-8519

Divergent Multicomponent Tandem Palladium-Catalyzed Aminocarbonylation-Cyclization Approaches to Functionalized Imidazothiazinones and Imidazothiazoles

Auto-tandem catalysis: A divergent multicomponent approach to imidazothiazinone and imidazothiazole derivatives starting from 2-(prop-2-ynylthio)imidazoles is developed. Imidazothiazinones are obtained from unsubstituted or monosubstituted substrates through an auto-tandem catalysis process that consists of two concatenated catalytic cycles, both catalyzed by PdI2.

ChemCatChem 2015, 7, No. 14, 2206-2213

Jaika Dörfler, Besnik Bytyqi, Sascha Hüller, Nicola M. Mann, Christian Brahms, Marc Schmidtmann, Sven Doye
An Aminopyridinato Titanium Catalyst for the Intramolecular Hydroaminoalkylation of Secondary Aminoalkenes [Full Paper]

Yingjun Zhu, Michaela Bauer, Lutz Ackermann
Late-Stage Peptide Diversification by Bioorthogonal Catalytic C-H Arylation at 23 °C in H2O [Communication]

Late-Stage Peptide Diversification by Bioorthogonal Catalytic C-H Arylation at 23 °C in H2O

C-H arylation of oligopeptides was achieved in aqueous media under exceedingly mild reaction conditions. The chemo- and site-selective nature of the late-stage diversification protocol illustrates the potential of our strategy for peptide ligation and fluorescence labeling (see scheme).

Chem. Eur. J. 2015, 21, No. 28, 9980-9983

Toan Dao-Huy, Birgit J. Waldner, Laurin Wimmer, Michael Schnürch, Marko D. Mihovilovic
Synthesis of endo- and exo-N-Protected 5-Arylated 2-Aminothiazoles through Direct Arylation: An Efficient Route to Cell Differentiation Accelerators [Full Paper]

Synthesis of endo- and exo-N-Protected 5-Arylated 2-Aminothiazoles through Direct Arylation: An Efficient Route to Cell Differentiation Accelerators

An improved protocol for the direct arylation of N-phenyl-N-benzyl(thiazol-2-yl)amines and regioisomeric 3-benzyl-N-phenylthiazol-2(3H)-imine is described. The two substrates for the arylation were obtained from a common starting material. In the latter case, the regioselectivity of arylation occurs exclusively in the 5-position.

Eur. J. Org. Chem. 2015, No. 21, 4765-4771

A Theoretical Probe of Mechanistic Trichotomy in RhIII-Catalyzed Annulation with Alkyne MIDA Boronates: Roles of Salt, Solvent, and Coupling Partner

The reaction mechanisms, the role of salts, solvent effects, and substrate scope in the RhIII-catalyzed C–H activation and annulation of N-(pivaloyloxy)benzamide and alkyne MIDA boronates have been investigated by DFT calculations.

Eur. J. Org. Chem. 2015, No. 21, 4772-4781

Chemoselective Pd-Catalyzed Isocyanide Insertion Reaction of Enaminones by C–H Functionalization: Hydrolysis or Cyclization through 1,3-Palladium Migration

A chemoselective palladium-catalyzed isocyanide insertion reaction of enaminones was developed. Amide derivatives were synthesized by this C–H functionalization and subsequent hydrolysis reactions, and 4-aminoquinoline derivatives were prepared by this C–H functionalization, which includes a 1,3-palladium migration in the process.

Eur. J. Org. Chem. 2015, No. 21, 4699-4709

Hui-Jun Chen, Hong-Dong Hao, Yikang Wu
Conversion of Dihydroartemisinic Acid into Dihydro-epi-deoxyarteannuin B [Full Paper]

Conversion of Dihydroartemisinic Acid into Dihydro-epi-deoxyarteannuin B

The conversion of dihydroartemisinic acid into dihydro-epi-deoxyarteannuin B, a difficult transformation that defied exhaustive efforts in a previous study, can now be readily achieved in excellent yields with Pd(OAc)2/CuCl2/MnO2. This finding makes it easier to access a range of other arteannuins and several potent trioxane-type antimalarial agents.

Eur. J. Org. Chem. 2015, No. 20, 4423-4427

Alexandre Vasseur, Jacques Muzart, Jean Le Bras
Ubiquitous Benzoquinones, Multitalented Compounds for Palladium-Catalyzed Oxidative Reactions [Microreview]

Ubiquitous Benzoquinones, Multitalented Compounds for Palladium-Catalyzed Oxidative Reactions

This review highlights the multifaceted properties of benzoquinone when it is involved in PdII-catalyzed oxidative reactions and presents mechanisms proposed in the literature.

Eur. J. Org. Chem. 2015, No. 19, 4053-4069

David Dailler, Grégory Danoun, Benjamin Ourri, Olivier Baudoin
Divergent Synthesis of Aeruginosins Based on a C(sp3)-H Activation Strategy [Full Paper]

Divergent Synthesis of Aeruginosins Based on a C(sp3)-H Activation Strategy

Go natural! A general and scalable access to the aeruginosin family of marine natural products (see graphic), exhibiting potent inhibitory activity against serine proteases, is described. The strategic use of two different Pd-catalyzed C(sp3)-H activation reactions led to the synthesis of aeruginosins 98A–C and 298A.

Chem. Eur. J. 2015, 21, No. 26, 9370-9379

Yue He, Jincheng Mao, Guangwei Rong, Hong Yan, Guoqi Zhang
Iron-Catalyzed Esterification of Benzyl C-H Bonds to Form α-Keto Benzyl Esters [Update]

Tomoaki Yamaguchi, Eiji Yamaguchi, Norihiro Tada, Akichika Itoh
Direct ortho-Hydroxylation of 2-Phenylpyridines using Palladium(II) Chloride and Hydrogen Peroxide [Communication]

Asymmetric Nickel-Catalysed Cross-Hydrovinylation of Two Terminal Alkenes

Pushing the boundaries: The asymmetric 1,2-hydrovinylation of styrene derivatives with terminal alkenes is realised by using a nickel catalyst and specially designed chiral NHC ligands to achieve a new level of complexity for the tail-to-tail cross-coupling of alkenes by C-H activation.

ChemCatChem 2015, 7, No. 11, 1639-1641

Tung T. Dang, Mickaële Bonneau, J. A. Gareth Williams, Hubert Le Bozec, Henri Doucet, Véronique Guerchais
Pd-Catalyzed Functionalization of the Thenoyltrifluoroacetone Coligands by Aromatic Dyes in Bis(cyclometallated) IrIII Complexes: From Phosphorescence to Fluorescence? [Full Paper]

Pd-Catalyzed Functionalization of the Thenoyltrifluoroacetone Coligands by Aromatic Dyes in Bis(cyclometallated) IrIII Complexes: From Phosphorescence to Fluorescence?

Bis(cyclometallated) IrIII complexes featuring acetylacetonate-type ligands directly conjugated to dyes are prepared by an original synthesis. The introduction of an aromatic pendant promotes fluorescence from the singlet state of the functionalized OO unit.

Eur. J. Inorg. Chem. 2015, No. 18, 2956-2964

Stefano Protti, Maurizio Fagnoni, Davide Ravelli
Photocatalytic C-H Activation by Hydrogen-Atom Transfer in Synthesis [Minireview]

Photocatalytic C-H Activation by Hydrogen-Atom Transfer in Synthesis

HATs off to photocatalysis! This review covers the recent advancements in the field of photocatalytic hydrogen-atom transfer (HAT) processes for C-H bond functionalization. Applications in organic synthesis, including the formation of C-C, as well as C-halogen, C-O (C=O) and C-N bonds, are presented.

ChemCatChem 2015, 7, No. 10, 1516-1523

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]

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]

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 2015, 7, No. 07, 1061-1063

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

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

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]

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

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

© Wiley-VCH 2013.