Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• , affording branched homoallylic alcohols in high yields with perfect branch selectivities. The intermediate of the reaction would be a nucleophilic allylcobalt(I) species generated via cleavage of the low reactive allylic C(sp3)–H bond of simple terminal alkenes. Keywords: alkenes; C–H activation; C(sp3)–H

Direct electrochemical generation of organic carbonates by dehydrogenative coupling

• Tile Gieshoff,
• Vinh Trieu,
• Jan Heijl and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2018, 14, 1578–1582, doi:10.3762/bjoc.14.135

• reactive chemicals. We present the first direct electrochemical generation of mesityl methyl carbonate by C–H activation. Although this reaction pathway is still challenging concerning scope and efficiency, it outlines a new strategy for carbonate generation. Keywords: anode; boron-doped diamond

• diamond (BDD) as electrode material has the capability to convert simple aromatic systems by direct C–H activation [21][22][23][24][25][26][27]. In contrast, other typical anode materials such as graphite, glassy carbon, or platinum tend to lead to electrode fouling when applying high positive potentials

• organic acetonitrile-based electrolyte system. Acetonitrile tolerates highly positive potential regimes, which are necessary for C–H activation of non-functionalized arenes. Since simple metal-based carbonate salts are not sufficiently soluble in organic media, the choice of carbonate source is crucial

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

• Santhivardhana Reddy Yetra,
• Zhigao Shen,
• Hui Wang and
• Lutz Ackermann

Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131

• by weakly-coordinating thiocarbonyl-assisted cobalt catalysis. Thus, carboxylates enabled ferrocene C–H nitrogenations with dioxazolones, featuring ample substrate scope and robust functional group tolerance. Mechanistic studies provided strong support for a facile organometallic C–H activation

• manifold. Keywords: amidation; C–H activation; cobalt; ferrocene; mechanochemistry; Introduction C–H activation has surfaced as a transformative tool in molecular sciences [1][2][3][4][5][6][7][8][9]. While major advances have been accomplished with precious 4d transition metals, recent focus has shifted

• ][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], prominently featuring transformative C–H nitrogenations [42][43] in an atom- and step-economical fashion [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. Within our program on cobalt-catalyzed C–H activation [60

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• intermediates and transition states. Keywords: catalysis; C–H activation; density functional theory; London dispersion; reaction mechanisms; Introduction For a long time, large and bulky substituents have intuitively been considered to act through unfavorable steric interactions, although London dispersion

• , ligand coordination, insertion) shown in Scheme 2 which served as the starting point of this investigation [30]. We now report on our computational findings supported by novel kinetic investigations to establish the reaction mechanism of this synthetically useful C–H activation and to elucidate the role

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• -dimethylpyrazole. The reaction has been extended to 1,2,3-triazoles, benzotriazole, and pyrazole. In the latter case, the use of (styryl)(aryl)-λ3-iodanes has also proved to be possible, with the styryl moiety being selectively transferred in the first step. The following step of C–H activation then gives access

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• regioselectivity for the C-6 position of bipyridinones and the C-8 position of quinoline N-oxides and tolerated a broad range of functionalities, such as halogens, ethers, or trifluoromethyl groups. Keywords: C–H activation; hypervalent iodine; indoleBX; indoles; pyridinones; rhodium catalysis; Introduction

• compounds with pyridinone, quinolone and indole cores. C–H functionalization of pyridinones and quinoline N-oxides. Scope and limitations of the Rh-catalyzed C–H activation of [1,2'-bipyridin]-2-one. Scope of the Rh-catalyzed peri C–H activation of quinoline N-oxides. Product modifications. Optimization of

• National Science Foundation (No. 200021_159920), the COST action CA15106 (C-H Activation in Organic Synthesis, CHAOS) and EPFL.

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• ; C–H activation; iodine; oxygenation; radicals; Introduction The oxidative activation of a C(sp3)–H bond in organic molecules to directly install various functional groups and new carbon–carbon networks is a topic of interest for researchers engaged in modern synthetic chemistry [1][2][3][4][5][6][7

• aqueous benzylic oxidations using polymeric iodosobenzene in the presence of inorganic bromide and montmorillonite-K10 [51]. In addition, a radical C–H activation strategy, using nonaqueous hypervalent iodine(III)/inorganic bromide systems that can work in organic solvents, was developed for the novel

• results of our extensive study and optimization of our radical C–H activation strategy for the intermolecular oxidative coupling between the benzylic secondary C–H bond and the O–H group of carboxylic acids (Scheme 1). Results and Discussion Benzylic C–H carboxylation can provide a convenient route to

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• that many of these useful reagents became a staple in synthetic chemistry laboratories [1][2]. Although hypervalent iodine reagents are commonly used in oxidation reactions, they have also found their own niche in useful C–C bond-formation and C–H activation reactions [3][4][5]. One such C–C bond

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• alkenylation reaction of pivalophenone N–H imine with an alkenyl phosphate. The reaction tolerates various substituted pivalophenone N–H imines as well as cyclic and acyclic alkenyl phosphates. Keywords: alkenylation; C–C bond formation; C–H activation; cobalt; imine; Introduction Transition-metal-catalyzed

• , directing group-assisted arene C–H activation reactions have been extensively studied over the last few decades to offer a broad array of atom and step-economical methods for the synthesis of functionalized aromatic compounds [1][2][3][4][5][6]. Among various C–H transformations, the introduction of alkenyl

• previously reported cobalt-catalyzed ortho C–H functionalization reactions [22][23][28][29], this regioselectivity may be ascribed to the role of the oxygen or fluorine atom as a secondary directing group to have an electrostatic interaction with the cobalt center during the C–H activation. For compound 3ja

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• in a ruthenium-catalyzed C–H activation reaction [36]. Most other reported transformations pass via the imidoyl chloride intermediates (equivalent to 10) to the amidine derivatives, which have been used in rearrangement reaction studies [9][37][38][39]. By these means also N,N’-bis(triflyl

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp² C–H bond activation in ball mills

• Zi Liu,
• Hui Xu and
• Guan-Wu Wang

Beilstein J. Org. Chem. 2018, 14, 430–435, doi:10.3762/bjoc.14.31

• corresponding N-halosuccinimides. Keywords: acetanilide; ball milling; C–H activation; halogenation; mechanochemistry; N-halosuccinimide; palladium catalysis; Introduction Aryl halides have been widely utilized in organic syntheses, which give access to a range of complex natural products [1][2]. However

• -bromosuccinimide (NBS) and N-iodosuccinimide (NIS), respectively, as the halogen source [30]. However, the mechanochemical ortho-halogenation using the cheaper palladium catalysts has not been reported yet. In continuing our interest in mechanochemistry [21][22][39][40][41] and C–H activation reactions [42][43][44

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• substituents and generate mixture of regioisomers in some cases. In 2012, the group of Qing [56] designed a copper-catalyzed oxidative trifluoromethylation of heteroarenes and electron-deficient arenes with TMSCF3 through direct C−H activation (Scheme 35). At first, the oxidative trifluoromethylation of 1,3,4

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• . They have also demonstrated a mechanochemical synthesis of 3-vinylindoles and β,β-diindolylpropionates by C–H activation. Substituted indoles and ethyl acrylates were reacted in presence of 10 mol % of Pd(OAc)2 and 1.2 equiv of MnO2 to afford highly substituted 3-vinylindoles using silica gel and

• phase processes. 4'-(N,N-dimethylamino)-4-nitroazobenzene with an equimolar amount of Pd(OAc)2 and 25 μL of glacial acetic acid (for LAG) resulted in regioselective C–H activation to give cyclopalladated complex E in 4.5 h where two Pd- and two azobenzene groups were involved. Treating this complex with

• another 1 equiv of Pd(OAc)2 resulted in a second C–H activation to give dicyclopalladated complex F in 7.5 h (Scheme 46). It is notable that the monocyclopalladated complexation generally takes 3 days in solution and dicyclopalladated complex in solution was never been identified [178]. Recently

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• with alkyne M. This is facilitated by coordination of L with RuII, followed by C–H activation to afford N. Migratory insertion of M on N generate O and subsequent reductive elimination of O afforded the desired compounds (Scheme 26). In another example Yuan et al. [88] demonstrated that a catalytic

Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

• Qin Zhu and
• Xinyu Liu

Beilstein J. Org. Chem. 2017, 13, 1168–1173, doi:10.3762/bjoc.13.115

• engineering and evolution of these proteins for biocatalyst application. Keywords: alkaloid biogenesis; biosynthetic divergency; C–H activation; halogenase; non-heme iron enzyme; Introduction Carbon–halogen (C–X) bonds are prevalent structural motifs in modern agrochemicals, pharmaceuticals and bioactive

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• halides have been extensively studied as substrates for the synthesis of phenols and aryl thiols. In very recent years, C–H activation represents a powerful strategy for the construction of functionalized phenols directly from various arenes. However, the synthesis of aryl thiols through C–H activation

• -catalyzed Ullmann-type coupling reaction has emerged as an effective method, allowing the synthesis of phenols and aryl thiols from aryl halides through C–O and C–S bond formation, respectively [5][6][7]. Very recently, the C–H activation has made revolutionary advances in organic synthesis because it

• allows an access to functionalized products from simple arenes, avoiding their pre-functionalization [8][9][10]. The synthesis of phenols has greatly benefited from C–H activation, but the application in the synthesis of aryl thiols is still yet to be reported. Both phenols and aryl thiols have similar

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• important problem in organic synthesis. Cross-coupling reactions provide avenues to these otherwise difficult reactions, but often require prefunctionalization of the coupling partners [1][2][3][4][5][6][7][8][9]. However, recent C–H activation research has enabled the use of further simplified starting

Self-optimisation and model-based design of experiments for developing a C–H activation flow process

• Alexander Echtermeyer,
• Yehia Amar,
• Jacek Zakrzewski and
• Alexei Lapkin

Beilstein J. Org. Chem. 2017, 13, 150–163, doi:10.3762/bjoc.13.18

• experimental efficiency. The self-optimisation approach required the least number of experiments to reach the specified objectives of cost and product yield, whereas the MBDoE approach enabled a rapid generation of a process model. Keywords: automated reaction system; C–H activation; design of experiments

• novel flow processes [18]. In this publication, we present an extension of this methodology, in which an initial process model is developed through a MBDoE methodology coupled with an automated self-optimisation flow system. This approach was tested on the Pd-catalysed C–H activation reaction of 1

• intermediate species B in a catalytic first step and consecutively transformed to product 2 in the second step, which comprises the C–H activation. In addition to the main reaction pathway, B can form the relatively unreactive resting state complex A, and compound 1 can also form a coordinated species 1∙HOAc

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• featuring an ambiphilic ligand, (quinolin-8-yl)dimesitylborane. Direct arylation could be achieved with 0.2 mol % catalyst and 3 equivalents of base (KO(t-Bu)) at 80 °C to afford TON ≈160–190 over 40 hours. Keywords: catalysis; C–C coupling; C–H activation; copper; direct arylation; Introduction Coupling

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• position. Conclusion In conclusion, a twofold C−H activation protocol applied to methyl 2,4-dianilinobenzoates facilitated a short and quick access to the cyclized products. Via the present route, indolo[3,2-a]carbazole derivatives are available in 3–4 steps based on commercially available starting

C–H Functionalization/activation in organic synthesis

• Richmond Sarpong

Beilstein J. Org. Chem. 2016, 12, 2315–2316, doi:10.3762/bjoc.12.224

• Richmond Sarpong Department of Chemistry, University of California, Berkeley, 841A Latimer Hall, Berkeley, CA 94720, USA 10.3762/bjoc.12.224 Keywords: C–H activation; C–H functionalization; The last decade has seen an explosion in research reports in the area of C–H functionalization/activation

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• (f in Scheme 2). The oxidative cyclisation after C–H activation of alkyl carbons is known for the formation of furan rings 21 (g in Scheme 2). 1.1 Pyrans 1.1.1 oxa-Michael addition: The oxa-Michael addition on an α,β-unsaturated thioester intermediate leads to oxygen heterocycles along with the

Synthesis of 2-substituted tetraphenylenes via transition-metal-catalyzed derivatization of tetraphenylene

• Shulei Pan,
• Hang Jiang,
• Yanghui Zhang,
• Yu Zhang and
• Dushen Chen

Beilstein J. Org. Chem. 2016, 12, 1302–1308, doi:10.3762/bjoc.12.122

• ][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. While most of these traditional approaches suffer from harsh conditions or complicated procedures, a novel strategy via transition-metal-catalyzed C–H activation has attracted great attention and emerged as a powerful methodology for the

Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

• William A. Nack,
• Xinmou Wang,
• Bo Wang,
• Gang He and
• Gong Chen

Beilstein J. Org. Chem. 2016, 12, 1243–1249, doi:10.3762/bjoc.12.119

• iodination, and Cu-catalyzed C−N cyclization enables a streamlined synthesis of tetrahydroquinolines bearing diverse substitution patterns. Keywords: iodination; palladium; remote C–H activation; tetrahydroquinoline; Introduction Tetrahydroquinoline (THQ) is an important N-heterocyclic scaffold found in

Synthesis of β-arylated alkylamides via Pd-catalyzed one-pot installation of a directing group and C(sp³)–H arylation

• Yunyun Liu,
• Yi Zhang,
• Xiaoji Cao and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2016, 12, 1122–1126, doi:10.3762/bjoc.12.108

• activation/functionalization has won splendid success [1][2][3][4][5][6]. Among the numerous elegant examples of C–H activation reactions, the DG (directing group) assisted C–H activation is obviously the most generally applicable tactic because of the irreplaceable function of the DG in facilitating the

• incorporation of a metal catalyst and controlling the site selectivity [7][8][9]. While benefiting the advantage of straightforward transformation from the C–H activation strategy, the utilization of a DG also brings unfavorable defection of step economics because an additional operation step in installing the

• subsequent C–H transformation [10][11][12]. The additional time in running the DG installation reaction and purification as well as related consumption of chemicals substantially undermine the efficiency of the C–H activation-based synthesis, which is against the principle of step economy [13][14]. In this