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

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• Takashi Nishikata Alexander R. Abela Shenlin Huang Bruce H. Lipshutz Department of Chemistry & Biochemistry, University of California, Santa Barbara, CA 93106, USA 10.3762/bjoc.12.99 Abstract Cationic palladium(II) complexes have been found to be highly reactive towards aromatic C–H activation of

• arylureas at room temperature. A commercially available catalyst [Pd(MeCN)4](BF4)2 or a nitrile-free cationic palladium(II) complex generated in situ from the reaction of Pd(OAc)2 and HBF4, effectively catalyzes C–H activation/cross-coupling reactions between aryl iodides, arylboronic acids and acrylates

• streamlined and efficient synthesis of boscalid, an agent produced on the kiloton scale annually and used to control a range of plant pathogens in broadacre and horticultural crops. Mechanistic investigations led to a proposed catalytic cycle involving three steps: (1) C–H activation to generate a cationic

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area. Keywords: C–H

• activation; chiral catalysis; diazo compounds; total synthesis; Introduction One of the major challenges met in organic synthesis is the formation of carbon–carbon bonds, in particular in a stereoselective way. Nucleophilic substitution reactions, radical reactions, cross-coupling reactions and the Heck

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• deprotection led to the target compound (+)-caprazol (19) [90][92]. For the synthesis of muraymycins, Ichikawa, Matsuda et al. furthermore developed a new route towards the epicapreomycidine-containing urea dipeptide unit via C–H activation (Scheme 3) [96][97]. For this purpose, the commercially available δ-N

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• for organic small-molecule functionalization [56][57][58]. One important application of photoredox catalysis is direct sp3 C–H activation and functionalization [59][60][61]. Among the recent advances, direct photoredox redox C–H activation of the α-position of amines has been an efficient and

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• ) could be obtained in 92% yield. In contrast to the two former cases, 4-(4-chlorobenzyl)pyrimidine (5e) could neither be oxidized at 100 °C nor at 130 °C. Competitive C–H activation of the 2 position is presumed to be the reason for this observation. Blocking this position by a methyl group (5f

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• , Darryl Rideout (coincidentally a Madison West High School classmate), Alanna Schepartz, Alan Schwabacher, George Trainor, Craig Wilcox, and Jeff Winkler. Ron Breslow had broad interests, with projects ranging from developing artificial enzymes, to novel anti-aromatic compounds, to remote C–H activation

Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

• Kazuhiro Hata,
• Hideto Ito,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2015, 11, 2737–2746, doi:10.3762/bjoc.11.295

• be a key step in the catalytic cycle consisting of transmetalation with arylsilane, C–H activation and reductive elimination [69]. While gold(I) complexes bearing various ligands are used as gold(III) precursors, it remains unclear whether ligands can still coordinate to the gold center or not under