Aryl substitution of pentacenes

• Andreas R. Waterloo,
• Anna-Chiara Sale,
• Dan Lehnherr,
• Frank Hampel and
• Rik R. Tykwinski

Beilstein J. Org. Chem. 2014, 10, 1692–1705, doi:10.3762/bjoc.10.178

• acetylide to pentacenequinone (Scheme 1) [21][35][36][37][38]. With these two ketones in hand, a second nucleophilic addition was initiated. Thus, commercially available aryl halides dissolved in dry THF were subjected to lithium halogen exchange at −78 °C using n-butyllithium. A substoichiometric amount of

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• aryls on thiophenes is an important research area in organic synthesis. The coupling of thiophene derivatives with aryl halides via a C–H bond activation/functionalisation [1][2][3][4][5][6][7][8][9][10][11][12] provides an environmentally attractive and cost-effective procedure for the preparation of a

• , 130.9, 130.8, 128.9, 127.2, 127.1, 117.0, 112.8, 13.9; Anal. calcd for C18H11Cl2NS (344.26): C, 62.80; H, 3.22; found: C, 63.01; H, 3.40. Regioselectivity of coupling reactions of 3-substituted thiophenes with aryl halides. Regioselectivity of the arylation of 2-methylthiophene with ortho-substituted

Palladium-catalysed cross-coupling reaction of ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds with aryl bromides: A direct protocol for the preparation of unsymmetrical biaryls

• Siphamandla Sithebe and
• Ross S. Robinson

Beilstein J. Org. Chem. 2014, 10, 1107–1113, doi:10.3762/bjoc.10.109

• [1][2][3][4][5]. Amongst them, the Suzuki–Miyaura cross-coupling reaction of aryl halides/triflates and organoboron compounds is one of the most documented and versatile cross-coupling reaction in the literature [6]. The use of organoboron compounds 1, 2 and 3 (Figure 1) as nucleophilic coupling

• palladium-catalyzed cross-coupling reaction of 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds with aryl bromides in only 10 minutes. Results and Discussion As shown in Scheme 1, 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds were easily prepared from aryl halides 7 via the reaction of

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• copper. The phosphorus coupling partners used are primary, secondary and tertiary phosphines, secondary phosphine–borane complexes, silyl- and stannylphosphines and phosphine chlorides. These phosphinating agents are coupled with aryl halides and triflates. Several general protocols are available

• . Palladium: In 1987, Tunney and Stille reported on the palladium-catalyzed synthesis of several aryldiphenylphosphines by cross-coupling aryl halides with (trimethylsilyl)diphenylphosphine or (trimethylstannyl)diphenylphosphine [169]. No base is required for this method. Trimethylsilyl compounds are

• K2CO3 or Cs2CO3 as a base. Buchwald et al. also added N,N’-dimethylethylenediamine 96 as a ligand to enhance the efficiency of the coupling. A secondary phosphine 25e was coupled with a variety of aryl halides 124 with electron-withdrawing or -donating substituents. The method tolerated the presence of

Clean and fast cross-coupling of aryl halides in one-pot

• Valerica Pandarus,
• Geneviève Gingras,
• François Béland,
• Rosaria Ciriminna and
• Mario Pagliaro

Beilstein J. Org. Chem. 2014, 10, 897–901, doi:10.3762/bjoc.10.87

• involves a boron-containing nucleophile (a variety of aryl and heteroaryl boronic acids, esters, Ar-BBN, trifluoroborate and other boron species) and vinyl- or aryl halides as the electrophilic species. The use of the Suzuki–Miyaura reaction became routine both in industry and in research laboratories

• Suzuki–Miyaura reaction when reactive functional groups are present in the electrophilic aryl halides [3][4]. Several homogeneous palladium catalysts of enhanced versatility for the cross-coupling of pinacolborane with aryl halides have since been introduced, for example by Buchwald and co-workers [5][6

• –Miyaura reaction. Results in Table 1 show that, following aqueous work-up, different unsymmetrically coupled compounds are obtained in good to excellent yields by coupling numerous different aryl bromides with different aryl halides, including heteroatom-containing aryls. In detail, entries 1 and 2 in

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• ][37][38]. Although the scope of the reaction was demonstrated to be quite broad, some limitations were noticed, especially in reactions involving aryl halides. For instance, primary amines and enolizable aldehydes were unusable in this process. As a part of our ongoing efforts to improve reliability

• room temperature. To the best of our knowledge, this constitutes the first manganese-mediated multicomponent reaction involving aryl halides as the source for nucleophilic species. Results and Discussion We previously reported that primary amines are not active in a Mannich-like multicomponent reaction

• aimed to use sulfonamides as potential synthetic equivalents of ammonia in a procedure that additionally avoids the preformation of an imine and/or an organometallic compound. Thus, we turned our attention to a multicomponent reaction between aldehydes, aryl halides and sulfonamides, which involves an

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

• complicates the recycling of the palladium catalyst since the two metals are difficult to separate. Sonogashira reactions can be used for the syntheses of terminal alkynes from aryl halides through the coupling with an alkyne source such as trimethylsilylacetylene (TMSA) or 2-methyl-3-butyn-2-ol (4) in

• of symmetrical and unsymmetrical diarylacetylenes resides not only in its low cost, but also in the possibility to carry out a conventional and a decarboxylative Sonogashira coupling reaction in sequence at the two sp carbons with two different aryl halides. Therefore a disubstituted alkyne can be

• . Therefore, the Pd-catalyzed coupling reaction of 4 or a propiolic acid derivative with 3-bromoaniline, in order to approach the synthesis of 3-aminophenylacetylene without the use of copper, would be highly desiderable [76]. Although many examples of copper-free Sonogashira reactions between aryl halides

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• electron-demand Diels–Alder reaction from 1,2,4-triazines bearing an acylamino group with a terminal alkyne side chain. Alkynes were first subjected to the Sonogashira cross-coupling reaction with aryl halides, the product of which then underwent an intramolecular inverse electron-demand Diels–Alder

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• -coupled using palladium catalysis. A one-pot sequence was also developed, first heating the boron diene with the dienophile, then adding an aryl halide, Pd(OAc)2 (5 mol %), K2CO3 (3 equiv) and finally refluxing the mixture in EtOH or MeOH for 5 h (Scheme 13). Reactions with various aryl halides

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

• . Kabalka developed improved conditions for the trifluoromethylation of aryl halides by carrying out the reaction in sodium dodecyl sulfate (SDS) and toluene, and by using TMSCF3 as a cheaper trifluoromethylating agent [65]. The reverse micelles appear to prevent the decomposition of TMSCF3 and provide an

• can be obtained via reaction of trifluoromethylthiolate with an electrophile like aryl halides. On the other hand, they can also be obtained by reacting aryl sulfides or disulfides under nucleophilic or radical conditions with a trifluoromethylation reagent [16][55][124]. Very recently, several

Oxidative 3,3,3-trifluoropropylation of arylaldehydes

• Akari Ikeda,
• Masaaki Omote,
• Shiho Nomura,
• Miyuu Tanaka,
• Atsushi Tarui,
• Kazuyuki Sato and
• Akira Ando

Beilstein J. Org. Chem. 2013, 9, 2417–2421, doi:10.3762/bjoc.9.279

• , agricultural chemicals, and functional materials because trifluoromethylation of such chemicals often significantly improves their performance [1][2][3][4][5][6]. To date, the trifluoromethylation of carbonyl compounds [7][8][9][10] and aryl halides [11][12][13] has been extensively explored. On the other hand

• used in place of (3,3,3-trifluoropropynyl)lithium, which can add to carbonyl compounds and couple with aryl halides through a zinc intermediate. For the 3,3,3-trifluoropropenyl synthon Yamazaki et al. reported the use of 2-(trifluoromethyl)-1-(phenylsulfenyl)vinyltrimethylsilane for the addition to

An easy direct arylation of 5-pyrazolones

• Hao Gong,
• Yiwen Yang,
• Zechao Wang and
• Chunxiang Kuang

Beilstein J. Org. Chem. 2013, 9, 2033–2039, doi:10.3762/bjoc.9.240

• of (hetero)arenes has emerged over the past few years as a rapidly growing field of syntheses [17][18][19][20][21][22][23][24][25][26]. The direct arylation of pyrazolones by using aryl halides offers a cleaner and more efficient method of meeting such goals and rare examples of such transformations

• have been described [15]. In this paper, we report a convenient and catalytic ligand-free synthesis of a series of 4-aryl-5-pyrazolones 3 from 5-pyrazolones 1 and aryl halides 2 (Scheme 1). The direct arylation of 5-pyrazolones by Pd-catalyzed C–H bond activation was utilized. Results and Discussion We

• were determined to be 0.1 equiv Pd(OAc)2 catalyst, 2.0 equiv Ag2CO3, acetonitrile, 90 °C, air atmosphere, 1:2 molar ratio of 1a to 2a, and 12 h reaction time. Under the optimized conditions (Table 1, entry 10), the scope of aryl halides was examined and the results are summarized in Table 2. The

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

• protocol has been developed employing an imidazole-based secondary phosphine oxide (SPO) ligated palladium complex (6) as a precatalyst. The catalytic coupling of aryl halides and olefins led to the formation of the corresponding coupled products in excellent yields. A variety of substrates, both electron

• of arylboronic acids with olefins, which were catalyzed by Pd(OAc)2 and employed N-bromosuccinimide as an additive under ambient conditions. The resulted biaryls have been obtained in moderate to good yields. Keywords: aryl halides; Heck reaction; olefins; palladium-complex; phosphine; Introduction

• the synthesis of leading molecules, a variety of preparative methodologies have been developed. Particularly, the Heck reaction is one of the most chosen methods in the synthesis of aryl-substituted olefins [7][8][9]. Aryl halides or arylboronic acids are among the most commonly employed arylpalladium

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• reactions of aryl halides with H–P compounds [5][6][7] and catalytic addition to nonpolar unsaturated carbon–carbon bonds [8][9][10][11]. In the field of radical chemistry, the addition of phosphorus radicals, mainly from H–P compounds, onto carbon–carbon multiple bonds [12][13][14][15] has held a special

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• consequence, the development of new methodologies for CAr–S bond formation still represents a challenge in organic chemistry (Figure 1). Nucleophilic substitution of aryl halides by a variety of sulfur anions, such as PhS−, 1-naphthylS−, S2−, thiourea anion (−SCNH(NH2)), thioacetate anion (MeCOS−) and

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

• 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

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• the literature that involve Pd-catalyzed cross coupling reactions of various aryl halides with different olefins. However, the major drawback of the Mizoroki–Heck-type reaction in the synthesis of 1,1-disubstituted olefins rests on its poor selectivity toward the formation of α-products [20][21][22

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• ][30]. Most of the literature reports are limited to aryl halides and indoles only. Clearly, each of these protocols has its own virtues; however, limitations still exist with respect to substrate scope, reagents and solvents, etc. Thus, palladium-catalyzed intra- and intermolecular cross-coupling

• are limited to aryl halides and phenols or alcohols only [36][60][61][62][63]. Functionalization of 4-substituted-7-azaindole scaffolds with 4-amino-2-fluorophenol was reported to be ineffective upon heating in the presence of a strong base such as KOt-Bu [35]. In addition, the N-oxide derivative of 4

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

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

• enantioselectivity for their reaction [25]. Organocatalytic sp2 C–H bond activation reactions The catalytic cross-coupling of arenes and aryl halides to construct biaryl compounds is an important area in synthetic organic chemistry. Transition-metal-catalyzed biaryl synthesis from unactivated arenes by C–H

• studied for this class of transformation. In 2010, three research groups independently reported organocatalytic biaryl synthesis from unactivated arenes and aryl halides [33][34][35]. Since these reactions follow a homolytic radical aromatic substitution mechanism (HAS) as pointed out by Studer and Curran

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

• tetramethylmagnolamine [6], and the antifungal diamine piperazinomycin [7] (Figure 1). A straightforward method for the formation of diaryl ethers is the Cu-catalyzed coupling of aryl halides with phenols, first reported by Fritz Ullmann in 1903 [8][9]. However, the classical protocol suffers from considerable

Hybrid super electron donors – preparation and reactivity

• Jean Garnier,
• Douglas W. Thomson,
• Shengze Zhou,
• Phillip I. Jolly,
• Leonard E. A. Berlouis and
• John A. Murphy

Beilstein J. Org. Chem. 2012, 8, 994–1002, doi:10.3762/bjoc.8.112

• ][15][16]. Neutral organic donors that can reduce aryl halides have been termed “super-electron-donors”. Our recent research has examined the remarkable chemical reactivity of such donors 1 and 2 as well as the related electron-donors 4 and 5 (Figure 1), with organic substrates [17][18][19][20][21][22

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

• )-catalyzed direct arylation of (benz)oxazoles with aryl halides; (a) Itami's procedure [80]; (b) Miura's procedure [81]. Dehydrogenative cross-coupling of (benz)oxazoles; (a) Pd(II)- and Cu(II)-catalyzed cross-coupling of benzoxazole with thiophene [82]; (b) Pd(II)- and Cu(II)-catalyzed cross-coupling of

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

• was developed by Lu and co-workers [33]. This one-pot reaction is based on a stepwise synthesis of indole derivatives reported by Cachi’s group, and involves, in the last step, a palladium-mediated cyclization of o-alkynylaniline derivatives in the presence of aryl halides [34]. In this process

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

• heterocyclization. In recent years, the direct hydroxylation of aryl halides has been developed by several groups by using palladium- or copper-catalyzed protocols. Whereas the reactions under copper catalysis work well for aryl iodides [45][46][47][48], the palladium-catalyzed hydroxylation also takes place with

Scaling up of continuous-flow, microwave-assisted, organic reactions by varying the size of Pd-functionalized catalytic monoliths

• Ping He,
• Stephen J. Haswell,
• Paul D. I. Fletcher,
• Stephen M. Kelly and
• Andrew Mansfield

Beilstein J. Org. Chem. 2011, 7, 1150–1157, doi:10.3762/bjoc.7.133

• demonstrated by Uozumi et al. [11], where carbon–carbon bond forming reactions of aryl halides and arylboronic acids under microflow conditions can be achieved quantitatively within 4 s residence time. However, the stability of the catalytic membrane was not discussed. Monolith based devices have shown good