Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• °C, but also the cheaper Ph3PAuCl/AgOTf gave respectable results. Surprisingly, AuBr3 was not able to promote this cascade reaction. A special feature of this approach is that when R4 is a o-alkynylbenzene a further Au-catalyzed cascade process involving C–H activation can occur to give the

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• . Cooperative [Au(I)]/menthol catalysis for the enantioselective intramolecular hydroamination of dienes. Acknowledgements Acknowledgment is made to Progetto FIRB “Futuro in Ricerca” Innovative sustainable synthetic methodologies for C–H activation processes, (MIUR, Rome) and the Università di Bologna.

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• results for nonaflate electrophiles. Otherwise, the scope is actually limited to six-membered vinyl sulfonates, and moderate yields were obtained with 2-alkyl substituted cyclohexenyl substrates. 3.1.2 Trifluoromethylation by means of C–H activation and an electrophilic CF3-source. In 2010, J.-Q. Yu and

• with lower yields than acetanilide. From the study of kinetic isotope effects in several experiments as well as of a Pd-insertion complex similarly to the work of J.-Q. Yu et al., the authors proposed a Pd(II)/Pd(IV) catalytic cycle starting with C–H activation of the substrate followed by oxidation of

• the complex with Umemoto’s reagent and completed by reductive elimination of the desired benzotrifluoride (Figure 2). 3.1.3 Perfluoroalkylation by means of C–H activation and a perfluoroalkyl radical-source. In contrast to the studies described above, the group of M. S. Sanford has developed a Pd

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes

• Yan-Chao Shi,
• Rong-Fei Yang,
• De-Wei Gao and
• Shu-Li You

Beilstein J. Org. Chem. 2013, 9, 1891–1896, doi:10.3762/bjoc.9.222

• enantioselectivity (up to 99% ee). Keywords: annulation; asymmetric catalysis; C–H activation; ferrocene; palladium; planar chirality; Introduction Chiral ferrocene derivatives have been widely applied to asymmetric catalysis, materials science, biomedical research, etc. [1][2][3][4]. Particularly, ferrocenes with

• ][28]. Despite these pioneering studies, the catalytic asymmetric methods to introduce ferrocenyl planar chirality are rather limited. Recently, a monoprotected amino acid was introduced as an efficient ligand in Pd-catalyzed enantioselective C–H activation by Yu and co-workers [29][30][31][32][33][34

Iron-catalyzed decarboxylative alkenylation of cycloalkanes with arylvinyl carboxylic acids via a radical process

• Jincan Zhao,
• Hong Fang,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2013, 9, 1718–1723, doi:10.3762/bjoc.9.197

• , numerous transition-metal-catalyzed processes, such as Pd [12][13][14][15][16][17][18], Cu [19][20][21][22][23], Ru [24][25][26][27], Rh [28][29][30][31], Co [32][33][34], Au [35][36], Ir [37][38][39], Fe [40][41][42][43] and other metals [44][45][46][47], have been developed for sp3 C–H activation

Aerobic radical multifunctionalization of alkenes using tert-butyl nitrite and water

• Daisuke Hirose and
• Tsuyoshi Taniguchi

Beilstein J. Org. Chem. 2013, 9, 1713–1717, doi:10.3762/bjoc.9.196

• precursor of a 5-amino-1,4-diol, and the access from simple aliphatic alkenes in one step is unprecedented. The functionalization of unreactive sp3 C–H bonds using a radical 1,5-hydrogen shift is an old methodology compared with modern transition metal-catalyzed C–H activation reactions [25][26][27], but

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• hydride-AIBN initiated radical cyclization [33][34]. In 2005, Player and co-workers reported a tandem Heck/Suzuki–Miyaura coupling process for the synthesis of (E)-3,3-(diaryl)oxindoles [35][36][37]. Recently, alkenylation of indolin-2-ones has been developed by palladium-catalyzed aromatic C–H activation

Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

• Satoshi Takebayashi,
• Tsubasa Shizuno,
• Takashi Otani and
• Takanori Shibata

Beilstein J. Org. Chem. 2012, 8, 1844–1848, doi:10.3762/bjoc.8.212

• ] catalyzed the C–H bond amidation of ferrocenes possessing directing groups with isocyanates in the presence of 2 equiv/Rh of HBF4·OEt2. A variety of disubstituted ferrocenes were prepared in high yields, or excellent diastereoselectivities. Keywords: amidation; C–H activation; C–H functionalization

• economy, and requires stoichiometric amounts of metal reagents. Functionalization of ferrocene derivatives by transition-metal-catalyzed enantioselective C–H activation is a potentially more atom-economical alternative. However, only a few catalytic C–H activation reactions of ferrocenes have been

• reported to date, and there is only one report of enantioselective C–H activation of ferrocenes [6][7][8][9]. Schmalz et al. reported the first catalytic C–H activation of ferrocenes using a Cu-catalyzed intramolecular carbene insertion into a Cp–H bond [6]. Further, they showed that the reaction could be

Iridium-catalyzed intramolecular [4 + 2] cycloadditions of alkynyl halides

• Andrew Tigchelaar and
• William Tam

Beilstein J. Org. Chem. 2012, 8, 1765–1770, doi:10.3762/bjoc.8.201

• , including homogeneous hydrogenation [1][2], C–H activation [3][4][5], asymmetric ring-opening reactions [6], and a variety of cycloisomerizations [7][8][9][10], and cycloadditions [11][12][13][14][15][16][17][18][19][20]. Traditionally these types of cycloisomerization and cycloaddition reactions are

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• domino processes. Review Intermolecular reactions involving alkenes Alkenylation reactions of indoles run through a key C–H activation step involving an electrophilic palladation and an electron-deficient Pd(II) catalyst. The mechanism of these reactions involves the generation of a σ-alkyl complex I

• providing conditions to access asymmetric biaryl compounds by dual C–H functionalization [55]. In 2007, Fagnou and co-workers combined, in a single catalytic cycle, the reactivity of electron-deficient palladium(II) complexes with electron-rich arenes (through an electrophilic C–H activation mechanism) and

• using the N-pivalyl-substituted indole in the absence of additives. From the mechanistic point of view, as depicted in Scheme 10, the C–H activation on the electron-rich indole, selectively directed by the strongly electrophilic behavior of the Pd(TFA)2 catalyst, is plausible giving the Pd(II

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• demonstrate that the resultant reactivity may be a powerful tool for the functionalization of C–H and E–H bonds. Keywords: ambiphilic reactivity; C–H activation; C–H functionalization; frustrated Lewis pair; metal carbene; multiple bond; Introduction Orbital cooperation has long been recognized as an

• the types of reactivity discussed thus far, there are several distinct routes to the functionalization of C–H (or E–H) bonds using metal–ligand multiply bonded FLPs. If C–H activation is effected by 1,2-addition across a M═E bond, then reductive elimination could result in a net C–H insertion of

• cleavage events at tert-butyl methyl ether (MTBE) (Scheme 14) [71][87]. For the (PNP)Ir system developed by Ozerov, it was found that an initial C–H activation of the most accessible methyl C–H bond in MTBE was followed by slow α-hydrogen elimination and reductive elimination of H2 to afford the Ir(I

C2-Alkylation of N-pyrimidylindole with vinylsilane via cobalt-catalyzed C–H bond activation

• Zhenhua Ding and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2012, 8, 1536–1542, doi:10.3762/bjoc.8.174

• C2-lithiation with a stoichiometric lithium base or indol-2-yl radicals generated from 2-halogenated indoles [12][13][14][15][16][17]. Examples of direct C2-alkylation via transition-metal-catalyzed C–H activation are still limited [18][19][20], while Jiao and Bach recently reported an elegant

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• Subhas Chandra Pan Department of Chemistry, Indian Institute of Technology Guwahati, North Guwahati, Assam, 781039, India 10.3762/bjoc.8.159 Abstract Organocatalytic C–H activation reactions have recently been developed besides the traditional metal-catalysed C–H activation reactions. The recent

• non-asymmetric and asymmetric C–H activation reactions mediated by organocatalysts are discussed in this review. Keywords: asymmetric; C–H activation; non-asymmetric; organocatalysis; organocatalytic; Introduction C–H activation reactions have recently been found to be a powerful method for the

• being one of the “key green chemistry research areas” [4][5][6]. This review describes the current “state of the art” in organocatalyzed C–H activation reactions and highlights recent advances in sp2 and sp3 C–H bond functionalization. For simplicity, iodide or hypervalent iodine-mediated metal-free C–H

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• ]. Due to the ambiphilic nature of the heterocyclic ring of coumarin, this core-structure undergoes a diverse array of coupling reactions, such as halogenations [25], cycloadditions [26][27][28][29][30][31][32], conjugate additions [33][34][35][36][37] and transition-metal-catalyzed C–H activation

Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous

• Elaine O’Reilly,
• Suzanne J. Aitken,
• Gideon Grogan,
• Paul P. Kelly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56

• ; selective C–H activation; Introduction Selective C–H activation remains a challenge for synthetic chemists, who often rely on differences in the steric and electronic properties of bonds to achieve regioselectivity [1]. The preparative-scale generation of hydroxylated intermediates can often provide

Pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes via a one-pot Sonogashira–Glaser cyclization sequence

• Dominik Urselmann,
• Dragutin Antovic and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1499–1503, doi:10.3762/bjoc.7.174

• halogen–metal exchange, transmetalation and isolation occasionally turns out to be tedious and in many cases the use of polar functionality in the substrate is considerably restricted. In recent years interesting examples of palladium-catalyzed direct C–H activation and arylation of (hetero)aromatics have

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• high-throughput screening protocol for evaluating chimeric, self-sufficient P450 biocatalysts and their mutants against a panel of substrates was developed, leading to the identification of a number of novel biooxidation activities. Keywords: biocatalysis; C–H activation; high-throughput screening

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• superseded by these venerable reactions [26][27] especially to the benefit of the medicinal and process chemist [28]. The currently lively area of metal-catalyzed C–H activation reactions (which has an early history but which commanded our attention by the publication of the Murai monograph [29][30]) is also

• exception [32][33][34], to rationalize ortho selectivity. The aromatic ring annulative chemistry, which can be achieved by C–H-activation mediated processes, perhaps best exemplified by gold-catalyzed reactions [35][36], is astonishing and defies retrosynthetic analysis. While as yet mostly empirically

• derived, mechanistically inadequately defined, and practically untested, the C–H activation methodologies will compete with, supersede, and replace our existing practices in synthetic aromatic chemistry in the next decade. Perhaps of interest to the in-depth reader of this Thematic Series are a number of

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• methodologies for C–H activation processes (MIUR, Rome), Università di Bologna.

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• compared to complex natural products, only a limited repertoire of synthetic transformations are utilised for their construction. Furthermore, many of the modern pioneering developments in organic synthesis including new highly selective and mild bond forming reactions such as metathesis and C–H activation

Photoinduced homolytic C–H activation in N-(4-homoadamantyl)phthalimide

• Nikola Cindro,
• Margareta Horvat,
• Kata Mlinarić-Majerski,
• Axel G. Griesbeck and
• Nikola Basarić

Beilstein J. Org. Chem. 2011, 7, 270–277, doi:10.3762/bjoc.7.36

• products [34]. Furthermore, suitably substituted phthalimides deactivate from the excited state by intramolecular H-abstractions to yield cyclization products, often benzazepinone derivatives [35][36][37]. Therefore, photoinduced homolytic C–H activation by phthalimide derivatives can, in principle, be

• -configuration. Conclusion N-(4-homoadamantyl)phthalimide (5) was synthesized and its photochemistry investigated. On excitation and population of the triplet state, 5 undergoes intramolecular homolytic C–H activation and gives products 6 and 7. The major product of the photochemical reaction is exo-alcohol 6

• ring closure to azetidinols and ring enlargement to azepinediones. High selectivity and high isolable yield of 6 in the photoreaction of 5 makes this photoinduced C–H activation useful in the synthesis of very complex derivatives with the homoadamantane skeleton with potential antiviral activity for

Backbone tuning in indenylidene–ruthenium complexes bearing an unsaturated N-heterocyclic carbene

• César A. Urbina-Blanco,
• Xavier Bantreil,
• Hervé Clavier,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2010, 6, 1120–1126, doi:10.3762/bjoc.6.128

• via an observed C–H activation route [19]. These results encouraged us to explore the electronic influence of backbone substitution in unsaturated NHCs with ruthenium–indenylidene complexes. Indenylidene catalysts are rapidly becoming quite popular [20][21], due to the availability of ruthenium

Synthesis of dihydrophenanthridines by a sequence of Ugi-4CR and palladium- catalyzed intramolecular C-H functionalization

• Florence Bonnaterre,
• Michèle Bois-Choussy and
• Jieping Zhu

Beilstein J. Org. Chem. 2008, 4, No. 10, doi:10.3762/bjoc.4.10

• Scheme 1. The Ugi four-component reaction between an o-iodobenzaldehyde 2, an aniline 3, an isocyanide 4 and a carboxylic acid 5 should afford an α-acetamido-α-phenylacetamide 6, which upon palladium-catalyzed C-H activation process should provide dihydrophenanthridine 1 [15][16][17][18][19][20][21