Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• be achieved by benzylic positioning as well as by choosing aryl bromides A (Scheme 3) that can be modified to the corresponding aryl alkynes C by cross coupling chemistry. Previously, we successfully utilized this combination of mutasynthesis and semisynthesis for 19-brominated ansamitocin

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• -36075 Vicenza, Italy 10.3762/bjoc.10.36 Abstract Two efficient protocols for the palladium-catalyzed synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides in the absence of copper were developed. A simple catalytic system consisting of Pd(OAc)2 and P(p-tol)3 using DBU as the base and THF as the

• solvent was found to be highly effective for the coupling reaction of 2-methyl-3-butyn-2-ol (4) with a wide range of aryl bromides in good to excellent yields. Analogously, the synthesis of aryl-2-methyl-3-butyn-2-ols was performed also through the decarboxylative coupling reaction of 4-hydroxy-4-methyl-2

• -pentynoic acid with aryl bromides, using a catalyst containing Pd(OAc)2 in combination with SPhos or XPhos in the presence of tetra-n-butylammonium fluoride (TBAF) as the base and THF as the solvent. Therefore, new efficient approaches to the synthesis of terminal acetylenes from widely available aryl

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• -reducing side-reactions to consume the aryllithium reagents 34a,b to some extent, as delineated below. Therefore, acid 10 was treated with an excess of 34a,b which were generated from aryl bromides, using either 2.5 equivalents thereof together with tert-butyllithium (t-BuLi, five equiv) or four

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

• trifluoromethylated arenes in good yields, and a variety of functional groups is tolerated under the mild conditions of the process. The reaction with aryl bromides or triflates is less efficient. The success of this Pd-catalyzed trifluoromethylation is due to highly hindered phosphorus ligands like BrettPhos, which

• effective reaction site for oxidative addition of Ar–X and the Pd(0) catalyst, increasing the yields and allowing the use of aryl bromides as starting materials (Table 3). Free alcohols and amines are compatible with the reaction conditions, which was not the case with S. L. Buchwald’s methodology. For the

• trifluoroacetate (MTFA) and cesium fluoride to generate the trifluoroacetate anion which decarboxylated under the reaction conditions (Figure 5). In most cases, the system does not necessitate the use of amine ligands excepted when aryl bromides are used instead of aryl iodides [81]. Aryl and heteroaryl products

Palladium(II)-catalyzed Heck reaction of aryl halides and arylboronic acids with olefins under mild conditions

• Tanveer Mahamadali Shaikh and
• Fung-E Hong

Beilstein J. Org. Chem. 2013, 9, 1578–1588, doi:10.3762/bjoc.9.180

• %) with heating at 60 °C in DMF (1 mL, Table 1, entry 14). It is worthy of noting that the coupling reaction was also performed in the absence of solvent, which gave 82% yield (Table 1, entry 15) of the coupled product. A wide range of olefins with different and diversely substituted aryl bromides were

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

• important for the regioselectivity of the arylation reaction. For instance, the less hindered ortho position is preferentially arylated (e.g., 14) when a meta substitutent is present on the benzylpicolinamide. Aryl bromides are much less reactive compared with aryl iodide substrates 4. This is in accordance

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• in the presence of (−)-sparteine (L1). Thus, addition of the aryllithiums (generated from the corresponding aryl bromides and lithium metal) to 19 occurs cleanly at −78 °C in toluene, and the resulting chiral cyclopentadienyllithiums 20 are transformed into ferrocenes 21 by treatment with FeCl2 or Fe

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

• variety of aryl chlorides using 5 mol % of Pd(OAc)2 associated to 10 mol % of Cy2P-o-biphenyl as the catalyst [26]. However, in most cases, such couplings were performed with aryl bromides or iodides [28][29][30][31][32][33][34][35][36][37][38][39]. The influence of mono- or diphosphines as ligands for

• –palladium catalysts have been employed by Fagnou and co-workers to promote intramolecular direct arylations of arenes [40]. A few examples of couplings of aryl bromides and iodides employing Pd–NHC complexes have also been reported [41][42][43][44][45]. For example, Sames and co-workers described the use of

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

• ], the catalyst loading can be decreased by at least 10-fold without drastically affecting the yield (Table 4, entry 1). Using the optimized reaction conditions, we examined the scope and the limitations of this catalytic system using various aryl bromides and heterocycles (Table 4). It appeared that the

• sterics of the aryl bromide had almost no impact on the reaction. Indeed, para-, meta- and ortho- substituted aryl bromides could be employed to arylate 6 in good yields. (Table 4, entries 1–3, 77–89%). However, ortho-disubstituted aryl bromide, such as bromomesitylene appeared to be too sterically

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

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

• under the same reaction conditions. Shi and co-workers reported a similar reaction with 1,10-phenanthroline as catalyst at 100 °C employing aryl iodides and aryl bromides as the substrates [34]. Whereas 40 mol % of the catalyst and 3.0 equivalents of potassium tert-butoxide as base were needed for the

• reaction with bromides, 20 mol % of the catalyst and 2.0 equivalents of potassium tert-butoxide were required for the reaction with iodides. Under these optimized conditions, different aryl bromides and aryl iodides were screened, and poor to good yields (27–89%) for the products 20 were observed (Scheme

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• Nicola Otto Till Opatz Institute of Organic Chemistry, University of Mainz, Duesbergweg 10–14, 55128 Mainz, Germany 10.3762/bjoc.8.122 Abstract In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low

• is still challenging. For the synthesis of alkaloids containing the diaryl ether linkage, we searched for efficient ligands for the Ullmann coupling of electron-rich aryl bromides as the substrates and performed a ligand screening using the model system 4-bromoanisole/4-methoxyphenol. To the best of

• decomposition of the ligands. Conclusion A collection of 56 multidentate ligands were screened in a model system for the Ullmann diaryl ether synthesis of electron-rich phenols and aryl bromides. Structurally diverse ligands showed a catalytic activity in the coupling, but none of the ligands showed a higher

Synthesis of oleophilic electron-rich phenylhydrazines

• Aleksandra Jankowiak and
• Piotr Kaszyński

Beilstein J. Org. Chem. 2012, 8, 275–282, doi:10.3762/bjoc.8.29

• increases its stability in the reaction medium. The hydrazines were isolated in 60–86% yields and purities >90%. The hydrazides 2 were obtained in 43–71% yields from aryl bromides 5, which were lithiated with t-BuLi and subsequently reacted with di-tert-butyl azodicarboxylate (DTBAD). Keywords

• lithiation of aryl bromides 5 with t-BuLi to avoid the formation of n-BuBr with n-BuLi and N-butylation of hydrazide 2. Hydrazide 2a was also obtained by the Cu2+-catalyzed addition [18] of arylboronic acid 6a [28] to DTBAD. The yields of both syntheses of 2a were comparable. The trichloroethyl hydrazide 3a

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• Discussion Synthesis of monovalent precursors Although aryl bromides, triflates and sometimes even chlorides react efficiently in Sonogashira cross-coupling reactions, our previous studies [103][104] showed that only the iodinated TLM, and in some rare cases the corresponding triflate-substituted wheel, is

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• arylation of heterocycles, including electron-rich azoles with aryl bromides, by using potassium phosphate as a base and phenanthroline as a ligand (Scheme 8) [47]. Over the past few decades, it has also been demonstrated that copper catalysis is not required in order to attain good yield and selectivity in

• methodologies for the C2- and C5-selective direct arylation proceeding by CMD and using aryl bromides and chlorides (Scheme 22b) [64]. In particular, the charge-control interaction was identified as the main discriminating parameter since the HOMO levels are identical at both C2 and C5 positions (Scheme 22a

Synthesis of fluoranthenes by hydroarylation of alkynes catalyzed by gold(I) or gallium trichloride

• Sergio Pascual,
• Christophe Bour,
• Paula de Mendoza and
• Antonio M. Echavarren

Beilstein J. Org. Chem. 2011, 7, 1520–1525, doi:10.3762/bjoc.7.178

• with high efficiency in a one-pot transformation. The reaction is totally compatible with aryl bromides, which do not undergo subsequent arylation reaction due to the inertness of gold(I) catalysts towards oxidative addition reactions under homogeneous conditions [63][64]. Cationic gold complexes 5 and

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• order to suppress the concurrent formation of 2-substituted indoles 60 by direct cyclization of o-alkynylaniline intermediates under the classical Sonogashira reaction conditions. Interestingly, aryl bromides were used as a third partner and may be added at the beginning of this one-pot reaction since

• reaction, two different aryl bromides are sequentially added to the primary aliphatic amine in the presence of a palladium(0) catalyst. The first selective, Pd-catalyzed mono-N-arylation leading to the corresponding γ-(N-arylamino)alkenes 69 is followed by a carboamination reaction, developed by the same

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• limitation due to the use of zinc as a reducing agent. Zinc has only moderate reducing properties, therefore its insertion into organic halides only proceeds smoothly in the case of aryl iodides and electron-poor substituted aryl bromides. The use of highly reactive zinc (Rieke-zinc) [20][21] solves the

• chloride and LiCl. Under these conditions, the relatively unreactive aryl bromides and chlorides readily react. Furthermore, sensitive functionalities are tolerated since the reactive arylmagnesium species generated is immediately trapped with zinc chloride (Scheme 7) [22]. Thus, methyl 3-bromobenzoate (37

• numerous applications in the preparation of new polyfunctional arylmagnesium reagents. Thus, the rapid reaction of Mg/LiCl with aryl bromides 90, 93 and 96 allows an expeditive synthesis of the new arylmagnesium derivatives 91, 94 and 97. Quenching with typical electrophiles provides the expected products

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• aryl bromides and chlorides [49][50][51]. Thus, in our case we employed the Pd-catalyzed Buchwald protocol [49] in an attempt to synthesise the desired dimethoxybenzo[b]furan derivatives. Thus, reaction of the previously prepared o-haloaryl alkynes 5–7 with KOH, in the presence of catalytic amounts of

• aryl bromides instead of aryl chlorides. In addition, we also observed better yields for the corresponding benzofuran derivatives 9 (Table 3, entries 5–9) derived from the starting o-alkynylhalobenzene derivatives 6, bearing the two methoxy groups in a 3,5-relationship relative to the halide. Moreover

Air-stable, recyclable, and time-efficient diphenylphosphinite cellulose-supported palladium nanoparticles as a catalyst for Suzuki–Miyaura reactions

• Qingwei Du and
• Yiqun Li

Beilstein J. Org. Chem. 2011, 7, 378–385, doi:10.3762/bjoc.7.48

• as base (Scheme 3). The typical experimental results are summarized in Table 4. The data presented in Table 4 show that the Cell–OPPh2–Pd0 catalyst was highly effective for both aryl bromides and aryl iodides. Most of these reactions proceeded rapidly and were complete within 20 min. The catalytic

• reactivity of aryl bromides was slightly lower than that of the corresponding aryl iodides and in these cases a prolonged time was required. The reaction of aryl chlorides with arylboronic acids was sluggish and gave only small amounts of products in acceptable times. The reusability of the supported

Studies on Pd/NiFe₂O₄ catalyzed ligand-free Suzuki reaction in aqueous phase: synthesis of biaryls, terphenyls and polyaryls

• Sanjay R. Borhade and
• Suresh B. Waghmode

Beilstein J. Org. Chem. 2011, 7, 310–319, doi:10.3762/bjoc.7.41

• catalyzed Suzuki reaction tolerated a wide range of functional groups such as NO2, CHO, Me, Cl, OMe, OH, NH2, and Ac. The aryl iodides and electron deficient aryl bromides showed excellent reactivity with phenyl- and 3-(hydroxymethyl)phenylboronic acid and led to the expected products in high yields within

• short reaction times. Bromobenzene and electron rich aryl bromides required a higher loading of palladium (1.0 mol %) to give comparable results. Both electron rich and electron deficient arylboronic acids gave biaryl products in good to excellent yields. Heterocyclic boronic acids required longer

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• hindered and functionalized aryl amines [22][23][24]. Aryl bromides are most frequently applied as substrates for the coupling of primary and cyclic secondary amines [17]. In the presence of a weak base such as caesium carbonate, many functional groups are tolerated, while NaOt-Bu has limitations when base

• -labile functional groups are present. Electron-neutral and electron-poor aryl bromides are suitable substrates [17], and ortho-substituents on the aryl halide are tolerated. In contrast, electron-rich aryl bromides give only poor results. Recently, the modular synthesis of indoles by a palladium

• palladium sources, reactions on a larger scale are possible. Sterically demanding N-nucleophiles, as well as cyclic and aromatic amino compounds, are suitable coupling partners with aryl bromides. In contrast to palladium catalysis, Ullmann-type coupling reactions tolerate atmospheric oxygen. However

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• carrying out the synthesis of aryltrifluoromethyl sulfides by generation CuSCF3 (from trifluoromethylthio mercury and -copper) in situ with the aryl halides. This not only reduces the number of steps but also increases the overall efficiency (Scheme 26). Aryl bromides can also be used but require higher

Suzuki–Miyaura cross-coupling reaction of 1-aryltriazenes with arylboronic acids catalyzed by a recyclable polymer-supported N-heterocyclic carbene–palladium complex catalyst

• Guangming Nan,
• Fang Ren and
• Meiming Luo

Beilstein J. Org. Chem. 2010, 6, No. 70, doi:10.3762/bjoc.6.70

• general study on the Suzuki–Miyaura reactions of 1-aryltriazenes under heterogeneous catalysis described to date. Previously, we reported an active and recyclable polystyrene-supported Pd–NHC (N-heterocyclic carbene) catalyst 1 (Scheme 1) for the Suzuki–Miyaura cross-coupling reactions of aryl bromides

•  5, entries 5, 6). Notably, good reactivity and chemoselectivity were achieved with 1-(4-bromophenyl)- and 1-(4-iodophenyl)-2-(pyrrolidin-1-yl)diazene (Table 5, entries 5, 6), showing that triazenes were more active than the corresponding aryl bromides and iodides under these reaction conditions

Solvent-free and time-efficient Suzuki–Miyaura reaction in a ball mill: the solid reagent system KF–Al₂O₃ under inspection

• Franziska Bernhardt,
• Ronald Trotzki,
• Tony Szuppa,
• Achim Stolle and
• Bernd Ondruschka

Beilstein J. Org. Chem. 2010, 6, No. 7, doi:10.3762/bjoc.6.7

• applied in solvent-free Pd-catalyzed Suzuki–Miyaura cross-coupling reactions of aryl bromides with phenylboronic acid, and the performances of the individual SRS were compared [33][34][36][37][38][39][40][41][42]. Results and Discussion Incorporation of KF–Al2O3 as a basic component in organic synthesis

• pH measurements of aqueous suspension of the pure aluminas. Investigating the influence of different SRS, the Pd(OAc)2-assisted Suzuki–Miyaura coupling of phenylboronic acid (1) with different aryl bromides 2 furnishing p-substituted biphenyls 3 (Scheme 1) was chosen. Reactions were performed in a

• ][39][40][41][42][57][58]. The yield of the coupling product depends on the reactivity of the aryl bromide and the reverse basicity of the SRS used. SRS1 (neutral γ-Al2O3) yielded the best results with the tested aryl bromides, followed by basic SRS2 (α-Al2O3) and SRS3 (γ-Al2O3). The preference of

Polyionic polymers – heterogeneous media for metal nanoparticles as catalyst in Suzuki–Miyaura and Heck–Mizoroki reactions under flow conditions

• Klaas Mennecke and
• Andreas Kirschning

Beilstein J. Org. Chem. 2009, 5, No. 21, doi:10.3762/bjoc.5.21

• following. Under these optimized conditions several examples of successful cross coupling reactions were achieved that are listed in Table 1. We included combinations of electron rich and electron deficient aryl bromides with functionalized boronic acids and yields of coupling products were commonly good to

• ] these clusters exert pronounced catalytic activity in solution at very low concentrations. This view is further supported by the fact that the catalytic species operating in the present case is able to promote Suzuki–Miyaura cross coupling reactions with aryl bromides while aryl chlorides are not good

• substrates under these standard conditions. This observation has been noted in many examples of heterogenized palladium salts or complexes [34]. Likewise, these species are commonly not reactive enough to promote the Heck–Mizoroki reaction with aryl bromides. It should be noted that under supercritical or