A³-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

• Jian-Lin Huang,
• Derek G. Gray and
• Chao-Jun Li

Beilstein J. Org. Chem. 2013, 9, 1388–1396, doi:10.3762/bjoc.9.155

• ). The Au@HS-CNC (4.4 mol %) decomposed at above 250 °C under an inert atmosphere, making them an attractive catalyst for catalytic reactions. The FT-IR spectra of CNC, HS-CNC and Au@HS-CNC (4.4 mol %) (Figure 4) showed absorbance bands around 2920 cm−1 due to the stretching vibration of the C–H bond in

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• . Moreover, recent experimental and theoretical reports are analyzed, which suggest the involvement of such intermediates in reaction mechanisms, particularly C–H bond-activation processes. Keywords: C–H bond activation; intermediate; platinum(II); reactive intermediates; three-coordinate; T-shaped; Review

• of olefins into M–H bonds, electrophilic attack at Pt–C bonds, and ligand cycloplatination [2]. Likewise, related Pd(II) complexes [3][4] are relevant in cross-coupling reactions and C–H bond-activation processes. The accessibility of three-coordinate Pd(II) species have been recently discussed [5

• complexes in solution will be discussed. Finally, participation of three-coordinate Pt(II) intermediates in reactions, mainly C–H bond-activation processes and ligand exchanges, will be analyzed. A thorough review on the bonding and stereochemistry of three-coordinate transition-metal compounds was

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• -pot procedure, the isolated yields of 3p–3r were moderate (45–52% yields) (Table 3, entries 1–3). The oxygenation of the adamantyl C–H bond was especially sluggish, giving the desired 1,4-diol 3s in only 23% yield (Table 3, entry 4). Similarly, in these reactions, the formation of reduced alcohols 5

• could be envisioned that this aerobic C–H bond oxygenation could be combined with the present remote C–H oxygenation with hydroperoxides, presumably resulting in direct formation of 1,4-dioxygenated compounds from nonoxygenated alkanes (Scheme 6). With this hypothesis, alkane 10 bearing a dibenzylic

• tertiary C–H bond (marked in green) was treated with the catalytic system of CuCl-1,10-phen (20 mol %) with NHPI in benzene/MeCN solvent under an O2 atmosphere (1 atm) (Scheme 7). The reaction with 20 mol % of NHPI proceeded as expected at 50 °C to afford a mixture of lactol 2i and 1,4-diols 3i in 29% and

Synthesis of phenanthridines via palladium-catalyzed picolinamide-directed sequential C–H functionalization

• Ryan Pearson,
• Shuyu Zhang,
• Gang He,
• Nicola Edwards and
• Gong Chen

Beilstein J. Org. Chem. 2013, 9, 891–899, doi:10.3762/bjoc.9.102

• phenanthridine 17 was obtained as a side product. Compound 17 is presumably generated through the PhI(OAc)2-mediated oxidation of the benzylic C–H bond to form a phenanthridinium intermediate 18, which then undergoes a removal of the PA group. Encouraged by these observations, we proceeded to explore whether the

• , forming 17 in excellent yield. We believe that PhI(OAc)2 serves as the oxidant for the initial Pd-catalyzed intramolecular C–H amination step, in which a PdII/IV catalytic manifold might be operative. Cu(OAc)2 is responsible for the subsequent oxidation of the benzylic C–H bond of dihydrophenanthridine

• States of America 10.3762/bjoc.9.102 Abstract We report a new synthesis of phenanthridines based on palladium-catalyzed picolinamide-directed sequential C–H functionalization reactions starting from readily available benzylamine and aryl iodide precursors. Under the catalysis of Pd(OAc)2, the ortho-C–H

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• production of 9 was more pronounced in EtOH having a C–H bond α to the oxygen, which likely served as a hydrogen donor (Table 1, entries 1 and 2). It should be mentioned that reduced material 9 may also be produced by Bu4NBr alone as observed in our previous study [28]. To elucidate the contribution of this

Spectroscopic characterization of photoaccumulated radical anions: a litmus test to evaluate the efficiency of photoinduced electron transfer (PET) processes

• Maurizio Fagnoni,
• Stefano Protti,
• Davide Ravelli and
• Angelo Albini

Beilstein J. Org. Chem. 2013, 9, 800–808, doi:10.3762/bjoc.9.91

• processes have found some application in synthesis for the mild and selective activation of aliphatic derivatives, in particular of a C–H bond [32]. The role of the acceptor radical anion in the above processes is thus decisive, and we report below a steady-state investigation of such species arising from

Complete σ* intramolecular aromatic hydroxylation mechanism through O₂ activation by a Schiff base macrocyclic dicopper(I) complex

• Albert Poater and
• Miquel Solà

Beilstein J. Org. Chem. 2013, 9, 585–593, doi:10.3762/bjoc.9.63

• and C–O bond formation, followed finally by a proton transfer to an alpha aromatic carbon that immediately yields the product [CuII2(bsH2m-O)(μ-OH)]2+. Keywords: aromatic hydroxylation; C–H bond activation; C–H functionalization; copper; DFT calculations; mechanism; Schiff base; Introduction Bearing

• beginning of the so-called σ* electrophilic mechanism described for ortho-hydroxylation towards phenolate [5]. It is worth noting that in the next reaction step, the aromatic H atom in the activated C–H bond of e is transferred as a proton to one neighboring aromatic carbon. Amazingly this step requires

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

• Ismail Özdemir,
• Nevin Gürbüz,
• Nazan Kaloğlu,
• Öznur Doğan,
• Murat Kaloğlu,
• Christian Bruneau and
• Henri Doucet

Beilstein J. Org. Chem. 2013, 9, 303–312, doi:10.3762/bjoc.9.35

• with heteroarenes. Keywords: aryl chlorides; atom-economy; C–H bond activation; C–H functionalization; carbenes; palladium; pyrroles; Introduction N-Heterocyclic carbenes (NHC) have emerged as an important class of ligands in the development of homogeneous catalysis [1][2][3][4][5][6][7][8][9]. Such

• palladium-catalyzed direct arylation of various heteroaromatics including pyrroles by a C–H bond activation using aryl halides has met great success in recent years, allowing the synthesis of a wide variety of arylated heteroaromatics in only one step [20][21][22][23][24][25]. However, there are still

• the palladium-catalyzed coupling of heteroarenes with aryl halides through a C–H bond activation has been largely explored. On the other hand, the influence of carbene ligands for such couplings remains largely unexplored [40][41][42][43][44][45][46][47]. Quite congested N-heterocyclic carbene

Alkyne hydroarylation with Au N-heterocyclic carbene catalysts

• Cristina Tubaro,
• Marco Baron,
• Andrea Biffis and
• Marino Basato

Beilstein J. Org. Chem. 2013, 9, 246–253, doi:10.3762/bjoc.9.29

• ; gold; hydroarylation; N-heterocyclic carbenes; Introduction The hydroarylation of alkynes (Scheme 1) is arguably one of the most intensively studied reactions leading to aromatic C–H bond functionalization [1][2][3][4][5][6][7]. In this reaction, the C–H bond of an arene adds formally trans to the

• higher catalytic activity and complete selectivity for the insertion of only one alkyne molecule into the aromatic C–H bond, whereas the palladium(II) complexes predominantly yielded the product deriving from the insertion of two alkyne molecules. The catalytic efficiency of complexes VI and VII was

• catalysis, such as, e.g., products of double-bond isomerisation or deriving from insertion of more than one alkyne molecule into the same arene C–H bond, were however never detected with Au catalysts. Only in the case of p-xylene was the reaction again fully selective, albeit sluggish. Variations of the

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

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

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

• Kyle F. Biegasiewicz,
• Michelle L. Ingalsbe,
• Jeffrey D. St. Denis,
• James L. Gleason,
• Junming Ho,
• Michelle L. Coote,
• G. Paul Savage and
• Ronny Priefer

Beilstein J. Org. Chem. 2012, 8, 1814–1818, doi:10.3762/bjoc.8.207

• and a phenyl group. In fact, the C–H bond of cubane has been shown to have ~31% s-character [20], compared to 25% for a simple alkane and 33% for an aromatic hydrogen. Due to the bulk of the cube it was initially envisioned that there would be high stereocontrol; however, the stereoselectivity was

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• -economical syntheses of annulated 1,2,3-triazoles were accomplished through copper-catalyzed intramolecular direct arylations in sustainable one-pot reactions. Thus, catalyzed cascade reactions involving [3 + 2]-azide–alkyne cycloadditions (CuAAC) and C–H bond functionalizations provided direct access to

• ; heteroarenes; triazoles; Introduction Transition-metal-catalyzed C–H bond functionalizations are increasingly viable tools for step-economical syntheses of various valuable bioactive compounds [1][2][3], which avoid the preparation and use of preactivated substrates [4][5][6][7][8][9][10][11][12][13][14][15

• for direct arylations of 1,2,3-triazoles. Thus, we showed that intermolecular copper-catalyzed C–H bond functionalizations could be combined with the Huisgen [51] copper(I)-catalyzed [52][53] [3 + 2]-azide–alkyne cycloaddition (CuAAC)[54], while C–H bond arylations of 1,2,3-triazoles were previously

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

• cyclization). A strategy involving an intramolecular C–H bond alkenylation of trisubstituted alkenes, followed by ring opening of the so-formed ring, was planned to achieve the diastereocontrolled formation of tetrasubstituted double bonds tethered to C-2 indole. The Pd(II)-catalyzed 5-endo-trig cyclization

• regenerates the Pd(0) species. The intramolecular Pd(II)-catalyzed reaction of the 1-allyl-2-indolecarboxamides 41 leads to the pyrazino[1,2-a]indoles 43 through the conversion of the olefinic C–H bond into a C–N bond (Scheme 21) [79]. The cyclization process resulted in the initially formed exomethylenic

Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts: Direct arylation of heterocycles

• Anthony R. Martin,
• Anthony Chartoire,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2012, 8, 1637–1643, doi:10.3762/bjoc.8.187

• . Keywords: C–H functionalization; direct arylation; heterocycles; N-heterocyclic carbenes; palladium; Introduction As a powerful addition to the classic palladium cross-coupling reactions, C–H bond functionalization has become a growing field of research over the last few years. The ubiquity of C–H bonds

• catalytic systems, and in the end to see whether the reactivity and application scope of these commercially available complexes could be broadened to include C–H bond functionalization transformations. We now report the activity of the [Pd(NHC)(cin)Cl] complexes 1–4 in the direct arylation of heterocycles

• utilised in various cross-coupling and, now, C–H-bond-functionalization reactions. Experimental General procedure for the direct arylation of heterocycles In a glovebox, a vial containing a stirring bar was charged with K2CO3 (124 mg, 0.9 mmol, 1.5 equiv) and pivalic acid (0.18 mmol, 18 mg, 30 mol %), and

Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

• Esteban P. Urriolabeitia,
• Eduardo Laga and
• Carlos Cativiela

Beilstein J. Org. Chem. 2012, 8, 1569–1575, doi:10.3762/bjoc.8.179

• -amino acids [11][12][13], due to the extraordinary interest in these delicate molecules as building blocks of peptides and proteins, and because of their relevant biological activity. In this context, we have recently reported C–H bond activation processes on a variety of arylglycines substituted at the

• mild reaction conditions (1 atm CO, 25 °C) and, mainly, because it occurs through C–H bond activation processes without the need to use prefunctionalized substrates. Typical aminocarbonylations catalysed by Pd usually start from the corresponding iodides or bromides, and require high CO pressures and

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

• [43]. Intramolecular addition of a benzylic C–H bond across a Zr(IV) phosphinidene has been reported by Stephan [32]. Several C–H cleavage reactions have also been reported across alkylidenes and alkylidynes [44][45][46], and these may be viewed as the microscopic reverse of the α-hydrogen

• carbene or nitrene (Scheme 13a). This would be formally related to carbene or nitrene insertions that have been shown to occur, among other cases, at dirhodium paddlewheel complexes [85], though the specific mechanism of C–H bond breaking (and hence the reaction selectivity) would be quite different. Such

• a transformation has not been realized with the early metal complexes that are most reactive toward C–H bonds, probably because reductive elimination is strongly disfavored relative to the 1,2-elimination of alkane. Another possibility would be an initial 1,2-addition of a C–H bond across M═E

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

• palladium-catalyzed, norbornene-mediated C2-alkylation reaction with a broad spectrum of alkyl bromides [21]. Over the past few years, our group and others have explored C–H bond functionalization reactions using cobalt complexes as inexpensive transition-metal catalysts [22], which often feature mild

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

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

• formation of C–C and C–X bonds [1][2][3]. The advantage of this method is that it does not require the functional group of the carbon atom, as in the conventional approach. Transition-metal-catalysed C–H bond functionalization reactions have been well-studied and different site-selective (regioselective and

• 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

• transformations will not be covered in this review. Review Organocatalytic sp3 C–H bond activation reactions Non-asymmetric variants tert-Amino effect: The “tert-amino effect” refers to the ring-closure reactions that proceed by redox processes for C–C and C–X bond formation within conjugated systems [7][8][9

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• ][7]. More recently, we [8], and others [9][10], have shown that alkylating the triazole group to give the triazolium group increases the strength of anion binding significantly by further polarising the C–H bond of the heterocycle. With one notable recent exception of an acyclic ferrocene-appended

(How) does 1,3,5-triethylbenzene scaffolding work? Analyzing the abilities of 1,3,5-triethylbenzene- and 1,3,5-trimethylbenzene-based scaffolds to preorganize the binding elements of supramolecular hosts and to improve binding of targets

• Xing Wang and
• Fraser Hof

Beilstein J. Org. Chem. 2012, 8, 1–10, doi:10.3762/bjoc.8.1

• for binding are favored for the pyrazole-substituted hosts 4H and 4Me, in the gas phase and in water, by values that range from 0.7–1.7 kcal/mol (Table 6). This result is not intuitive. The steric gearing that could possibly be provided by the methyl groups comes only from C–H bonds: A single C–H bond

Efficient synthesis of 1,3-diaryl-4-halo-1H-pyrazoles from 3-arylsydnones and 2-aryl-1,1-dihalo-1-alkenes

• Yiwen Yang,
• Chunxiang Kuang,
• Hui Jin,
• Qing Yang and
• Zhongkui Zhang

Beilstein J. Org. Chem. 2011, 7, 1656–1662, doi:10.3762/bjoc.7.195

• moderate to excellent yields. 1,3-Diaryl-4-halo-1H-pyrazoles are found to be important intermediates that can easily be converted into 1,2,5-triaryl-substituted pyrazoles via Pd-catalyzed C–H bond activation. Keywords: C–H bond activation; cycloaddition; dihaloalkenes; pyrazole; sydnones; Introduction

Hypervalent iodine(III)-induced methylene acetoxylation of 3-oxo-N-substituted butanamides

• Wei-Bing Liu,
• Cui Chen,
• Qing Zhang and
• Zhi-Bo Zhu

Beilstein J. Org. Chem. 2011, 7, 1436–1440, doi:10.3762/bjoc.7.167

• ][3][4][5][6][7][8][9][10][11][12][13][14]. Indeed, direct oxidative C–H bond functionalization provides an atom-economical and efficient pathway to achieve these goals. Representative examples have been elegantly utilized not only in academic research, but also in the production of a variety of fine

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• under mild conditions. Toste’s group reported a gold(I)-catalyzed sequential cycloisomerization/sp3 C–H bond functionalization (Scheme 39) of 1,5-enynes 218 and 1,4-enallenes to yield tetracyclododecane 219 and tetracyclotridecane derivatives, respectively [97]. These transformations represent rare

• examples of sp3 C–H bond insertion via a cationic gold(I)–carbenoid intermediate. 4.3 Cycloadditions Intramolecular [M + N]-type cycloaddition reactions are powerful tools for accessing complex molecular frameworks [98]. Several gold-catalyzed [3 + 2] [99], [4 + 2] [100][101][102][103][104][105], and [4

• triggered a new reaction mode of furan–yne cyclization and delivered a new class of tetracyclic system 263 rather than a phenol (Scheme 46) [141]. Insertion of a C–H bond into a metal–carbenoid is a highly useful method for forming a new carbon–carbon bond. An atypical gold–carbenoid induced cleavage of a

The role of silver additives in gold-mediated C–H functionalisation

• Scott R. Patrick,
• Ine I. F. Boogaerts,
• Sylvain Gaillard,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2011, 7, 892–896, doi:10.3762/bjoc.7.102

• profile of 1 appears linked to bond acidity, and was found to functionalise selectively the most electron-deficient C–H bond in a substrate. Unfortunately, the reactivity of 1 was limited to bonds with a pKa value below 30.4 [12]. Current gold research has shown that silver salts can not only improve

• ) and the silver salt (AgY) may generate the active “AuY” complex. However, this was disproved by the successful reaction using AgCl. This would implicate [AuCl(IPr)] as the possible active species. This has already been discounted since it was shown to be unreactive in the model C–H bond

• achieved. The high electronegativity of the silver counter ion is of great importance. Finally, evidence of an interaction between silver salts and the substrate suggests that silver activates the aryl C–H bond and is then implicated in a transmetalation reaction with gold to provide the product. The value