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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
Marc Steinmetz, Kirika Ueda, Stefan Grimme, Junichiro Yamaguchi, Sylvia Kirchberg, Kenichiro Itami, Armido Studer
Mechanistic Studies on the Pd-catalyzed Direct C-H Arylation of 2-Substituted Thiophene Derivatives with Arylpalladium Bipyridyl Complexes [Full Paper]
The counteranion does the job! Reactions of 2-substituted thiophenes with cationic PhPdbipy complexes afforded either the corresponding C(4) or C(5)-phenylated thiophene derivatives depending on the counteranion present. DFT calculations revealed that reactions occur via carbopalladation and not via electrophilic palladation.
Chem. Asian J., February 14, 2012, DOI: 10.1002/asia.201101011
Frédéric Frébault, Nuno Maulide
Total Synthesis and Structural Revision of the Piperarborenines: When Photochemistry Meets C-H Activation [Highlight]
Activate and reiterate: The activation of C(sp3)-H bonds is a highly desirable transformation because molecular complexity can be increased at the expense of the most simple and readily available organic linkage. In recent contributions this approach was used for coupling reactions with small all-carbon rings, as exemplified by the sequential C-H activation steps in an elegant total synthesis of the piperarborenines (see scheme; DG=directing group).
Angew. Chem. Int. Ed., February 13, 2012, DOI: 10.1002/anie.201108592
Tanguy Saget, Sébastien J. Lemouzy, Nicolai Cramer
Chiral Monodentate Phosphines and Bulky Carboxylic Acids: Cooperative Effects in Palladium-Catalyzed Enantioselective C(sp3)–H Functionalization [Communication]
Teaming up: The important indoline scaffold is provided with enantiomeric ratios of up to 98:2 in palladium(0)-catalyzed C(sp3)–H activations of aryl triflates. The key is the combination of the electron-rich monodentate Sagephos and the bulky 9H-xanthene-9-carboxylic acid. Both participate in a highly cooperative manner in the enantiodetermining concerted-deprotonation-metalation step (see scheme, Tf=triflate).
Angew. Chem. Int. Ed., February 3, 2012, DOI: 10.1002/anie.201108511
Chihiro Tsukano, Masataka Okuno, Yoshiji Takemoto
Palladium-Catalyzed Amidation by Chemoselective C(sp3)-H Activation: Concise Route to Oxindoles Using a Carbamoyl Chloride Precursor [Communication]
Quite select: A new strategy was developed for the synthesis of various oxindoles from carbamoyl chlorides. Under the optimum reaction conditions, with Ad2PBu as a ligand, tBuCONHOH as an additive, and a CO atmosphere, selective C(sp3)-H activation proceeded in the presence of a C(sp2)-H bond. Ad=adamantyl.
Angew. Chem. Int. Ed., February 2, 2012, DOI: 10.1002/anie.201108889
Alvaro Iglesias, Rosana Alvarez, Angel R. de Lera, Kilian Muñiz
Palladium-Catalyzed Intermolecular C(sp3)-H Amidation [Communication]
Dual capacity: A new palladium-catalyzed intermolecular sequence consisting of the C-H activation and amidation of methyl groups relies on N-fluorobis(phenylsulfonyl)imide (NFSI) as both the oxidant and the nitrogen source. The reaction provides the corresponding arylamines as bissulfonimides along with HF as the only by-product. Both experimental and computational results suggest the involvement of a monomeric palladium(IV) intermediate.
Angew. Chem. Int. Ed., February 1, 2012, DOI: 10.1002/anie.201108351
Joanna Wencel-Delord, Corinna Nimphius, Frederic W. Patureau, Frank Glorius
[RhIIICp*]-Catalyzed Dehydrogenative Aryl-Aryl Bond Formation [Communication]
![[RhIIICp*]-Catalyzed Dehydrogenative Aryl-Aryl Bond Formation](http://www.wiley-vch.de/util/hottopics/img/anie201107842.gif "[RhIIICp*]-Catalyzed Dehydrogenative Aryl-Aryl Bond Formation")
Directed, undirected! Rhodium(III)-catalyzed double CH bond activation (one directed, one undirected) provides an efficient route to biaryls (see scheme; DG=directing group). Significant kinetic isotope effects for both reaction partners and H/D scrambling between them are interesting experimental findings. While the mechanism is still unclear, a rhodium(V) species is invoked in the catalytic cycle.
Angew. Chem. Int. Ed., January 27, 2012, DOI: 10.1002/anie.201107842
Lutz F. Tietze, Tim Hungerland, Alexander Düfert, Ina Objartel, Dietmar Stalke
Synthesis of Tetrasubstituted Alkenes through a Palladium-Catalyzed Domino Carbopalladation/C-H-Activation Reaction [Full Paper]
A new twist: Tetrasubstituted helical alkenes are promising lead structures as molecular machines for storage devices. Helical alkenes (2) were synthesized diastereoselectively by a palladium-catalyzed domino carbopalladation/C-H-activation reaction.
Chem. Eur. J., January 19, 2012, DOI: 10.1002/chem.201103209
Marius Mewald, Julia A. Schiffner, Martin Oestreich
A New Direction in C-H Alkenylation: Silanol as a Helping Hand [Highlight]
Director's cut: Not only conventional alcohols but also silanols can act as directing groups in oxidative palladium(Ii)-catalyzed C-H alkenylations. The silicon-tethered hydroxy groups are “traceless”, thereby facilitating the regioselective C-H activation of toluene derivitives as well as phenols (see scheme).
Rong Zhu, Stephen L. Buchwald
Combined Oxypalladation/C-H Functionalization: Palladium(II)-Catalyzed Intramolecular Oxidative Oxyarylation of Hydroxyalkenes [Communication]
An efficient protocol has been developed for the intramolecular oxidative oxyarylation using a PdII-catalyzed tandem oxypalladation/C-H functionalization strategy. This methodology allows rapid access to tetrahydro-2H-indeno-[2,1-b]furan frameworks from simple hydroxyalkenes. The reactivity of this process is orthogonal to that of Pd0-catalyzed transformations, enabling the divergent modification of a single molecule.
Davide Ravelli, Maurizio Fagnoni
Dyes as Visible Light Photoredox Organocatalysts [Highlight]
Tomorrow always dyes! Organic dyes (e.g., Rose Bengal, Eosin Y) have been recently used as versatile photoredox organocatalysts in place of metal complexes (e.g., Ru2+ salts). Accordingly, photoinduced electron transfer reactions induced by excited dyes were exploited in various synthetic processes. The reactions were performed under metal-free conditions and visible light irradiation.
Yohei Mizuta, Yasushi Obora, Yosuke Shimizu, Yasutaka Ishii
para-Selective Aerobic Oxidative C-H Olefination of Aminobenzenes Catalyzed by Palladium/Molybdovanadophosphoric acid/2,4,6-Trimethylbenzoic Acid System [Communication]
Pick of the bunch: Oxidative C-H olefination of aminobenzenes with acrylates was achieved using a palladium/molybdovanadophosphoric acid (HPMoV)/2,4,6-trimethylbenzoic acid (TMBA) system under O2 (1 atm) in DMF. The highly regio- and stereoselective C-H olefination of basic substrates such as aminobenzenes is important in organic synthesis; (E)-para-alkenyl-substituted aminobenzenes were produced in high yields.
Giulia de Petris, Giancarlo Angelini, Ornella Ursini, Marzio Rosi, Anna Troiani
Linking Ion and Neutral Chemistry in C-H Bond Electrophilic Activation: Generation and Detection of HO2. Reactive Radicals in the Gas Phase [Communication]
The flip side: Both the charged and uncharged products formed by C-H bond electrophilic activation have been experimentally detected in the gas phase. The HO2. radical is formed by a process involving the prototypical oxygen-centered radical cation O2.+ and the methane derivative CH2F2.
René Jarling, Masih Sadeghi, Marta Drozdowska, Sven Lahme, Wolfgang Buckel, Ralf Rabus, Friedrich Widdel, Bernard T. Golding, Heinz Wilkes
Stereochemical Investigations Reveal the Mechanism of the Bacterial Activation of n-Alkanes without Oxygen [Communication]
Anaerobic growth of the bacterium strain HxN1 with n-hexane gives nearly equal amounts of (2R,1'R)- and (2S,1'R)-(1-methylpentyl)succinate, which are formed by the radical addition of the hydrocarbon to fumarate (see scheme). The highly selective attack on the pro-S hydrogen atom at C2 of n-hexane is associated with inversion of the configuration at C2 during binding to fumarate and exhibits isotopic discrimination against a C-2H bond.
Sandeep R. Kandukuri, Julia A. Schiffner, Martin Oestreich
Aerobic Palladium(II)-Catalyzed 5-endo-trig Cyclization: An Entry into the Diastereoselective C-2 Alkenylation of Indoles with Tri- and Tetrasubstituted Double Bonds [Communication]
The endo trick: An endo ring closure onto the trigonal β carbon atom of α,β-unsaturated acceptors that are tethered to the indole nitrogen atom followed by amide cleavage enables the diastereoselective C-2 alkenylation of indoles with fully substituted double bonds. The carboxy group functions as a synthetically useful temporary tether (see scheme).
Jin Xie, Huamin Li, Jiecong Zhou, Yixiang Cheng, Chengjian Zhu
A Highly Efficient Gold-Catalyzed Oxidative C-C Coupling from C-H Bonds Using Air as Oxidant [Communication]
A breath of fresh air: The title reaction has been developed for the coupling of amines with nitroalkanes and different unmodified ketones using air as the sole oxidant under mild reaction conditions. The safe, convenient, and environmentally benign process, as well as the low catalyst loading, short reaction time, and good yields make this protocol very practical (see scheme).
Zhikun Ni, Qian Zhang, Tao Xiong, Yiying Zheng, Yan Li, Hongwei Zhang, Jingping Zhang, Qun Liu
Highly Regioselective Copper-Catalyzed Benzylic C-H Amination by N-Fluorobenzenesulfonimide [Communication]
Primary target: A practical and effective copper-catalyzed amination strategy for synthesizing various benzylic amines from benzylic hydrocarbons is described (see scheme; DCE=1,2-dichloroethane). Xylene substrates can undergo diamination reactions using this method. The remarkable preference for primary over secondary benzylic C-H bonds has been observed for the first time.
Tobias Gensch, Marika Rönnefahrt, Regina Czerwonka, Anne Jäger, Olga Kataeva, Ingmar Bauer, Hans-Joachim Knölker
Snapshot of the Palladium(II)-Catalyzed Oxidative Biaryl Bond Formation by X-ray Analysis of the Intermediate Diaryl Palladium(II) Complex [Communication]
PdII caught in the act: The diaryl PdII intermediate of a PdII-catalyzed oxidative biaryl bond formation proceeding via a double C-H bond activation has been isolated and fully characterized, including an X-ray crystal structure analysis (see figure). Stabilization due to chelation by adjacent pivaloyloxy and acetyl groups has allowed the isolation of this long-sought crucial intermediate. On gentle warming, the complex is transformed into a carbazole product, and the catalytically active PdII species is regenerated by oxidation with CuII.
Tianfei Liu, Xinxin Shao, Yaming Wu, Qilong Shen
Highly Selective Trifluoromethylation of 1,3-Disubstituted Arenes through Iridium-Catalyzed Arene Borylation [Communication]
The old one two: A sequential iridium-catalyzed borylation and copper-catalyzed trifluoromethylation of arenes is described (see scheme; Pin=pinacol). The reaction is conducted under mild reaction conditions and tolerates a variety of functional groups. The advantages of this tandem procedure are demonstrated by the late-stage trifluoromethylation of a number of biologically active molecules.
Qiang Liu, Ya-Nan Li, Hui-Hui Zhang, Bin Chen, Chen-Ho Tung, Li-Zhu Wu
Reactivity and Mechanistic Insight into Visible-Light-Induced Aerobic Cross-Dehydrogenative Coupling Reaction by Organophotocatalysts [Full Paper]
Light work: With visible-light irradiation (λ>450 nm), a mild, simple and efficient metal-free photocatalytic system for the facile construction of sp3–sp3 C-C bonds between tertiary amines and activated C-H bonds has been achieved (see scheme). Electron spin resonance measurements offer direct evidence for the formation of superoxide radical anions (O2−.) during visible-light irradiation.
Andreas Uhe, Markus Hölscher, Walter Leitner
Carboxylation of Arene C-H Bonds with CO2: A DFT-Based Approach to Catalyst Design [Full Paper]
A quick fix: The direct carboxylation of unactivated arene C-H bonds with CO2 using ruthenium(II) pincer complexes as catalysts is investigated by DFT methods (see scheme). The turnover frequencies of various catalyst modifications are predicted and optimized catalyst systems are designed.
Vedhagiri S. Thirunavukkarasu, Chien-Hong Cheng
Pd-Catalyzed Multiple C-H Functionalization to Construct Biologically Active Compounds from Aryl Aldoxime Ethers with Arenes [Communication]
Functional fluorenones: Aromatic aldoxime ethers react with unactivated arenes catalyzed by palladium complexes to give biologically active fluoren-9-ones (see scheme). Multiple C-H bond activation and an oxidative cyclization are involved in the reaction.
Martin H. G. Prechtl, Michael Teltewskoi, Anton Dimitrov, Erhard Kemnitz, Thomas Braun
Catalytic C-H Bond Activation at Nanoscale Lewis Acidic Aluminium Fluorides: H/D Exchange Reactions at Aromatic and Aliphatic Hydrocarbons [Communication]
Nanoscopic amorphous Lewis acidic aluminium fluorides, such as aluminium chlorofluoride (ACF) and high-surface aluminium fluoride (HS-AlF3), are capable of activating C-H bonds of aliphatic hydrocarbons. H/D exchange reactions are catalysed under mild conditions (40 °C).
Alison E. Wendlandt, Alison M. Suess, Shannon S. Stahl
Copper-Catalyzed Aerobic Oxidative C-H Functionalizations: Trends and Mechanistic Insights [Review]
The rapid recent growth of Cu-catalyzed aerobic oxidative C-H functionalization reactions belies the extensive history of such transformations, which can be traced to the discovery of alkyne coupling reactions by Glaser in the 19th century. Recent studies implicate multiple possible mechanisms for these reactions, ranging from classical single-electron-transfer pathways to the involvement of novel organometallic intermediates.
Puneet Kumar, Janis Louie
Nickel-Mediated Cycloaddition by Two Sequential C-H Activations [Highlight]
Double the fun: The future of cross-coupling chemistry lies in the development of cleaner synthetic methods for carbon–carbon bond formation. A recent advancement in the field of nickel-catalyzed C(sp2)–C(sp3) cross-couplings (see scheme) via two C-H activations represents a major step forward.
Armido Studer, Dennis P. Curran
Organocatalysis and C-H Activation Meet Radical- and Electron-Transfer Reactions [Essay]
A radical outlook: Recently published “organocatalytic C-H activation reactions” have now been interpreted as base-promoted homolytic substitutions. The addition of an aryl radical to an arene followed by deprotonation (see above) and electron transfer form part of the chain reaction. Although these new results are not conceptual breakthroughs, they could be experimental breakthroughs because they presage new transformations in radical (anion) chemistry.
Shuichi Yanagisawa, Kenichiro Itami
tert-Butoxide-Mediated C-H Bond Arylation of Aromatic Compounds with Haloarenes [Highlight]
Say halo, wave goodbye: Recently, several research groups have reported that the C-H bond arylation of aromatic compounds with haloarenes can be promoted by potassium or sodium tert-butoxide, without the addition of any exogenous transition metal species. These serendipitous discoveries are highlighted and summarized.
Lutz Ackermann
Transition-Metal-Catalyzed Carboxylation of C-H Bonds [Highlight]
CO2 in a fix: Gold and copper complexes of N-heterocyclic carbenes recently enabled efficient direct carboxylation of (hetero)arenes having moderately acidic C-H bonds under remarkably mild reaction conditions (IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene).
Timothy Newhouse, Phil S. Baran
If C-H Bonds Could Talk: Selective C-H Bond Oxidation [Minireview]
Let the molecule do the talking: If C-H bonds could talk, they would tell stories of inductive effects, conjugation, hyperconjugation, steric hindrance, and strain release. These stories are told from the perspective of synthetic planning and draw from the immense body of literature on the topic.
Frederic W. Patureau, Frank Glorius
Oxidizing Directing Groups Enable Efficient and Innovative C-H Activation Reactions [Highlight]
Come in! The use of internal oxidants, embedded in the directing group, in C-H activation reactions can lead to higher levels of selectivity and reactivity under milder conditions (see examples). An internal oxidant can be defined as a covalent bond within one of the coupling substrates which oxidizes the metal catalyst. This should open up new avenues in the field of C-H activation.
© Wiley-VCH 2011.
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