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
Bromine dominates! The promiscuous aliphatic halogenase WelO5 selectively brominated 12-epi-fischerindole U through late-stage enzymatic functionalization of an unactivated sp3 C−H bond, which showed eight times higher antibacterial activity against the human pathogen Staphylococcus aureus. This approach highlights the promise of enzyme-mediated late-stage aliphatic halogenation in tuning the potency of antibiotics.
Qin Zhu, Matthew L. Hillwig, Yohei Doi, Xinyu Liu
ChemBioChem, February 04, 2016, DOI: 10.1002/cbic.201500674. Read article
Ring, ring! 1-Methylpyrrole-2-carboxylic acid and 1-methylindole-3-carboxylic acid are efficiently annulated with alkynes by using the inexpensive and stable-to-water [RuCl2(p-cymene)]2 catalyst with Cu(OAc)2⋅H2O as the oxidant and as acetate provider by C−H and O−H bond activation to give their respective pyrrole- and indole-fused isocoumarin derivatives. These catalytic reactions can be performed in DMF and competitively in water.
Keisham S. Singh, Sneha G. Sawant, Pierre H. Dixneuf
ChemCatChem, February 02, 2016, DOI: 10.1002/cctc.201501261. Read article
This is aN-Nulation! A redox-neutral cobalt(III)-catalyzed synthesis of free indoles featuring an N−N bond cleavage has been achieved. An increase of reactivity could be observed on tuning the directing group at the hydrazine-β-nitrogen atom, which turned out to be the crucial factor for the reaction.
Andreas Lerchen, Suhelen Vásquez-Céspedes, Frank Glorius
Angew. Chem. Int. Ed., February 02, 2016, DOI: 10.1002/anie.201510705. Read article
1-Substituted imidazoles, acylacetylenes, and aldehydes undergo a facile and regioselective cascade reaction under metal-free conditions to give (imidazol-2-yl)methyl-1,3-propanediones through C-2–H functionalization. These reactive building blocks and drug precursors, which have previously been inaccessible, are now readily available by the developed reaction.
Boris A. Trofimov, Ludmila V. Andriyankova, Lina P. Nikitina, Kseniya V. Belyaeva, Anastasiya G. Mal'kina, Irina Yu. Bagryanskaya, Andrei V. Afonin, Igor A. Ushakov
Eur. J. Org. Chem., February 1, 2016, DOI: 10.1002/ejoc.201501617. Read article.
Luca Alessandro Perego, Laurence Grimaud, Fabio Bellina
Adv. Synth. Catal., January 26, 2016, DOI: 10.1002/adsc.201500888. Read article.
The IrIII complex [TpMe2Ir(C6H5)2(N2)] [TpMe2 = hydridotris(3,5-dimethylpyrazolyl)borate] reacts with different olefins to yield organometallic compounds that derive from allylic C–H activations in processes that also generate organic coupling products that involve the vinylic positions of the olefin.
Crispín Cristóbal, Laura L. Santos, Rubén Gutiérrez-González, Eleuterio Alvarez, Margarita Paneque, Manuel L. Poveda
Eur. J. Inorg. Chem., January 19, 2016, DOI: 10.1002/ejic.201501253. Read article.
Two in one: The Ir–imine-functionalized protic N-heterocyclic carbene (pNHC) complex was obtained through a chelate-assisted C2-H bond activation in the cationic Nimidazole-Ir complex. New homo- and heterodinuclear complexes could be prepared by in situ deprotonation of either the neutral Nimidazole-Ir complex or the Ir pNHC complex followed by addition of metal precursors (see scheme).
Fan He, Marcel Wesolek, Andreas A. Danopoulos, Pierre Braunstein
Chem. Eur. J., January 15, 2016, DOI: 10.1002/chem.201504030. Read article.
Ligands of tomorrow: Chiral spirocyclic sultams are rapidly assembled in a [3+2] annulation from N-sulfonyl ketimines and alkynes. The transformation is catalyzed by rhodium complexes equipped with the atropchiral biaryl Cpx ligand, and provides the sultams in excellent yields and high enantioselectivities.
Manh V. Pham, Nicolai Cramer
Chem. Eur. J., January 11, 2016, DOI: 10.1002/chem.201504998. Read article.
Chains linked: Through the interplay of high-resolution scanning tunneling microscopy imaging and density functional theory calculations, the stepwise homocoupling of alkyl chains on Cu(110) is demonstrated, proceeding from the intact chain, via the dehydrogenative intermediates, to the final coupling products.
Liangliang Cai, Qiang Sun, Chi Zhang, Yuanqi Ding, Wei Xu
Chem. Eur. J., January 8, 2016, DOI: 10.1002/chem.201504152. Read article.
AAA-rated strategy: A method for the synthesis of propargylamines by a three-component reaction of aldehydes, amines, and alkynes (A3-coupling) followed by a [3+2] cycloaddition for the preparation of 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines is reported. The coupling uses SnCl2 as the catalyst under solvent-free conditions to generate the desired products in good to excellent yields with high diastereoselectivity.
Shakil N. Afraj, Chinpiao Chen
Asian J. Org. Chem., January 08, 2016, DOI: 10.1002/ajoc.201500471. Read article
Access the inaccessible: A copper-catalyzed 8-amide chelation-induced remote C-H amination of quinolines has been developed (see scheme). This direct amination with readily available azodicarboxylates proceeded with perfect C5-regioselectivity offering amino-substituted 8-aminoquinolines in high yields (up to 96 %).
Harekrishna Sahoo, Mallu Kesava Reddy, Isai Ramakrishna, Mahiuddin Baidya
Chem. Eur. J., January 7, 2016, DOI: 10.1002/chem.201504207. Read article.
Origin of the activation: The inner surface structures of the pore wall in mesoporous α-Fe2O3 are mainly comprised of turbostratic ribbons and K crystal faces. They show excellent catalytic performance for methane activation, during which the C-H bonds are converted into C-O bonds in an O2 atmosphere at 140 °C (see figure).
Bing Dong, Zhen Han, Yongbo Zhang, Youyi Yu, Aiguo Kong, Yongkui Shan
Chem. Eur. J., January 7, 2016, DOI: 10.1002/chem.201503183. Read article.
Arylation contemplation: Novel dinuclear palladium complexes bearing acetoxy ligands are synthesized and characterized by X-ray crystal analysis. The complexes are utilized for the arylation of 2-ethylthiophene with iodobenzene to give ethylphenylthiophenes with high β selectivity. The β-arylation is also applied to a variety of iodoarenes and thiophenes not bearing conjugated carbonyl substituents.
Yohei Maki, Takahiro Goto, Naofumi Tsukada
ChemCatChem, January 05, 2016, DOI: 10.1002/cctc.201501132. Read article
A blockbuster catalyst: Well-defined ruthenium(II) phosphinous acid (PA) complexes were identified as powerful catalysts for highly selective C-H arylations with ample scope, which enabled low catalyst loadings and gave step-economical access to blockbuster drugs. Mechanistic studies were supportive of a PA-assisted C-H activation.
Daniel Zell, Svenja Warratz, Dmitri Gelman, Simon J. Garden, Lutz Ackermann
Chem. Eur. J., December 22, 2015, DOI: 10.1002/chem.201504851. Read article.
Alkynes on a gold Tr(i)p! Various peptides and one model protein were functionalized with ethynyl moieties at their tryptophan residues using Waser’s reagent, TIPS-EBX, under gold(I) catalysis (see scheme; TIPS=triisopropylsilyl). The reaction proceeded in a regio- and chemoselective manner leading to C2 substitution at the tryptophan residues only. Subsequently, the terminal alkyne was used to label one of the model peptides with a fluorophore by means of copper-catalyzed click chemistry.
Morten Borre Hansen, František Hubálek, Troels Skrydstrup, Thomas Hoeg-Jensen
Chem. Eur. J., December 22, 2015, DOI: 10.1002/chem.201504462. Read article.
Rhoad to alkaloids! A Rh-catalyzed intramolecular C-H bond activation/annulation of aldehydes and alkyne–amines provides a novel efficient method for the synthesis of various protoberberine salts and natural products in high yield under mild reaction conditions.
Jayachandran Jayakumar, Chien-Hong Cheng
Chem. Eur. J., December 22, 2015, DOI: 10.1002/chem.201504378. Read article.
In two shakes: Oxidative annulation by double C-H activation/alkyne insertion reaction was achieved by a nickel/NHC system. A Ni0/NiII catalytic cycle is proposed as the main catalytic cycle. The alkyne plays a double role as a two-component coupling partner and as a hydrogen acceptor.
Luis C. Misal Castro, Atsushi Obata, Yoshinori Aihara, Naoto Chatani
Chem. Eur. J., December 21, 2015, DOI: 10.1002/chem.201504596. Read article.
Influential solvent: Efficient access to atropo-enantioenriched biaryl moieties through asymmetric direct C-H activation, by using enantiopure sulfoxide as both the directing group and chiral auxiliary, is reported (see scheme). The key role of 1,1,1,3,3,3-hexafluoropropanol (HFIP) solvent is investigated.
Quentin Dherbassy, Geoffrey Schwertz, Matthieu Chessé, Chinmoy Kumar Hazra, Joanna Wencel-Delord, Françoise Colobert
Chem. Eur. J., December 18, 2015, DOI: 10.1002/chem.201503650. Read article.
The crucial role of gold in the transformation of ethane to ethene and dihydrogen is observed in the reaction between C2H6 and Au2VO3+ clusters with closed-shell electronic structures. The first C-H activation is initiated by gold rather than an oxygen species. The Au-Au dimer formed during the reactions plays important roles in converting ethane into ethene and making dihydrogen energetically more favorable.
Ya-Ke Li, Zi-Yu Li, Yan-Xia Zhao, Qing-Yu Liu, Jing-Heng Meng, Sheng-Gui He
Chem. Eur. J., December 17, 2015, DOI: 10.1002/chem.201503676. Read article.
Jitan Zhang, Danyang Li, Hui Chen, Binjie Wang, Zhanxiang Liu, Yuhong Zhang
Adv. Synth. Catal., December 16, 2015, DOI: 10.1002/adsc.201500727. Read article.
Three is a magic number: On treatment of triazoles with [Rh2(C7H15CO2)4], the rhodium catalyst plays three roles, denitrogenation, C-H bond activation, and stereoselective cyclization, providing a new method for heterocycle synthesis. Intramolecular C-H bond insertion takes place at the benzylic position to give pyrrolidines and related heterocycles in good yields.
Masato Senoo, Ayana Furukawa, Takeshi Hata, Hirokazu Urabe
Chem. Eur. J., December 14, 2015, DOI: 10.1002/chem.201503823. Read article.
Cationic N-heterocycles are an important class of organic compounds, largely present in natural and bioactive compounds. In this review, recent advancements in the synthesis and applications of cationic N-heterocycles through C−H activation reactions are summarized. The new C−H activation reactions described in this review are preferred over their classical counterparts.
Parthasarathy Gandeepan, Chien-Hong Cheng
Chem. Asian J., December 14, 2015, DOI: 10.1002/asia.201501186. Read article
DDAism: Dehydrogenative cycloadditions have attracted significant attention in synthetic chemistry. This Minireview highlights the recent efforts towards the development of dehydro or dehydrogenative Diels–Alder reactions to construct diverse aromatic compounds by a concerted pathway or a stepwise process.
Wenbo Li, Liejin Zhou, Junliang Zhang
Chem. Eur. J., November 24, 2015, DOI: 10.1002/chem.201503571. Read article.
A directed heterogeneous C-H activation/halogenation reaction catalyzed by readily synthesized Pd@MOF nanocatalysts was developed (see scheme). The heterogeneous Pd catalysts used were a novel and environmentally benign Fe-based metal–organic framework (MOF) (Pd@MIL-88B-NH2(Fe)) and the previously developed Pd@MIL-101-NH2(Cr). Very high conversions and selectivities were achieved under very mild reaction conditions and in short reaction times.
Vlad Pascanu, Fabian Carson, Marta Vico Solano, Jie Su, Xiaodong Zou, Magnus J. Johansson, Belén Martín-Matute
Chem. Eur. J., October 20, 2015, DOI: 10.1002/chem.201502918. Read article.