Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• de Sfax, Faculté des Sciences de Sfax, Route de la Soukra km 4, 3038 Sfax, Tunisia 10.3762/bjoc.13.278 Abstract The reactivity of 2-bromo- and 2,5-dibromoselenophenes in Pd-catalyzed direct heteroarylation was investigated. From 2-bromoselenophene, only the most reactive heteroarenes could be

• synthesis of unsymmetrical 2,5-di(hetero)arylated selenophene derivatives in three steps from selenophene. Keywords: C–H bond activation; catalysis; heteroarenes; palladium; selenophene; Introduction (Hetero)aryl-substituted selenophenes represent a class of molecules which exhibit useful physical

• described. Therefore, the reactivity of 2-bromo- and 2,5-dibromoselenophenes in Pd-catalyzed direct couplings with heteroarenes needed to be investigated. Herein, we wish to report on the reactivity of 2-bromoselenophene, 2,5-dibromoselenophene and 2-aryl-5-bromoselenophenes in palladium-catalyzed direct

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• additional step of intramolecular cyclisation. An alternative radical chain process was also considered this time, involving notably the reaction of radical 28 with CF3SO2Cl to produce CF3• and intermediate 29. Csp2–CF3 bond-forming reactions Trifluoromethylation of arenes and heteroarenes: The pioneering

• light bulb. This way, they were able to considerably extend the scope of application of the reaction. Indeed, electron-rich five-atom heteroarenes, electron-deficient six-atom heteroarenes as well as unactivated arenes were easily converted into their trifluoromethylated analogues in high yields (Scheme

•  25). Although the regioselectivity of the reaction was overall excellent for heteroarenes, it proved to be less satisfying for substituted arenes. Further investigations allowed the authors to propose a detailed mechanism, represented in Scheme 25. After excitation of the ruthenium catalyst through

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• arenes and heteroarenes: In 1991, Langlois and co-workers reported the first trifluoromethylation of aromatic compounds with sodium trifluoromethanesulfinate under oxidative conditions (Scheme 34) [16]. The scope was quite narrow with electron-rich aromatics and mixtures of regioisomers were often

• trifluoromethylation with CF3SO2Na are highly efficient, the original Langlois’ conditions were nevertheless applied to a series of heteroarenes. Li and co-workers reported the synthesis of 3-trifluoromethylcoumarins 64 by Cu(I)-catalysed trifluoromethylation with CF3SO2Na and t-BuOOH in a continuous-flow reactor [61

• -position of pyridinones facilitated the trifluoromethyl radical attack [63]. Catalytic amounts of phosphovanadomolybdic acid, a heteropolyacid catalyst (HPA), was used by Mizuno, Yamaguchi and co-workers for the oxidative C−H trifluoromethylation of arenes and heteroarenes in the presence of CF3SO2Na and

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• ethers of α-halooximes 2) in the reaction with organometallic compounds may lead to further developments in this promising methodology. Addition of arenes to conjugated nitrosoalkenes Besides common C-nucleophiles, nitrosoalkenes can react with nucleophilic arenes and heteroarenes. Gilchrist and Roberts

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

• /bjoc.13.162 Abstract Nitrogen heteroarenes form an important class of compounds which can be found in natural products, synthetic drugs, building blocks etc. Among the diverse strategies that were developed for the synthesis of nitrogen heterocycles, oxidative dehydrogenation is extremely effective

• . This review discusses various oxidative dehydrogenation strategies of C–C and C–N bonds to generate nitrogen heteroarenes from their corresponding heterocyclic substrates. The strategies are categorized under stoichiometric and catalytic usage of reagents that facilitate such transformations. The

• nitrogen heteroarenes. Keywords: aerobic oxidation; bioinspired Flavin mimics; nitrogen heteroarenes; organo catalytic; oxidative dehydrogenation; Introduction By virtue of their presence in bioactive natural products and active pharmaceutical ingredients, nitrogen heterocycles and heteroaromatics form

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• , Russia Ivanovo State University of Chemistry and Technology, 7 Sheremetyevskii prosp., Ivanovo, 153000, Russia 10.3762/bjoc.13.152 Abstract The arylation of mono-, di- and tetra-meso-bromophenyl-substituted porphyrins with the heteroarenes containing “acidic” C–H bonds, such as benzoxazole

• our purpose, while the third system proved to be most versatile and afforded corresponding mono-, di-, tri- and even tetraarylated derivatives of porphyrins. Keywords: arylation; copper catalysis; heteroarenes; palladium catalysis; porphyrins; Introduction Porphyrins play an outstanding role in many

• investigations we abandoned this catalytic protocol which was shown to be improper for our reagents and tried another one, proposed by Z.-Z. Huang [36] which employs both Pd(II) and Cu(II) catalyst precursors. The reactions of zinc porphyrinates 1 and 2 with heteroarenes were catalyzed with Pd(OAc)2/Cu(OAc)2 (20

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

• facilitate C–H hydroxylation of benzoic acids and heteroarenes [55]. An amidation reaction between benzoic acid and 2-(pyridine-2-yl)isopropylamine gave N-(2-(pyridine-2-yl)isopropyl)benzamides, which could be hydroxylated at the ortho position in moderate to excellent yields. The reaction was promoted by a

• were converted to the corresponding phenols. Moreover, heteroarenes, such as pyridine and thiophenes, could also give hydroxylated products under their conditions. In 2016, Jana and co-workers used N-(8-quinolinyl)benzamides as starting materials, and ortho-hydroxylation occurred in the presence of a

• (Scheme 28) [57]. Muti-halogenated arenes also gave the corresponding phenols when treated under the above mentiond conditions. An mechanistic investigation showed that NaOt-Bu was a crucial reagent which played dual roles in affording the active CuOt-Bu from CuCl2, and deprotonation of heteroarenes

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• with halides (Ka ≈ 103–104 M−1 in acetone-d6). Not surprisingly, a higher number of hydrogen bonds with an anion correlated with the higher stability of the receptor/anion complex. 1,2,3-Triazole-based catalysts for the dearomatization of N-heteroarenes The Mancheno group recently explored triazole

• the titration of L4 with TBAC [37]. Catalysts L3 and L4 were successfully applied to the asymmetric dearomatization of electron-deficient N-heteroarenes (Scheme 3). Various nitrogen-containing heterocycles such as pyridines [36], quinolines [38], isoquinolines [38], etc. were reacted with TrocCl to

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

• Florin Albota,
• Mino R. Caira,
• Constantin Draghici,
• Florea Dumitrascu and
• Denisa E. Dumitrescu

Beilstein J. Org. Chem. 2016, 12, 2503–2510, doi:10.3762/bjoc.12.245

• the compounds of type Het-COCH2Hal the indolizination of aromatic heterocycles by the Chichibabin synthesis could be extended to link two heteroarenes. This method overcomes the difficulties encountered in obtaining biheteroaryls through palladium-catalyzed cross-coupling reactions. In addition, the

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• trifluoromethylated heterocycles, such as indone and carbostyril derivatives. Based on their important biological functions in nature and the synthetic potential of α-pyrones for the construction of a variety of fluorescent heteroarenes, we decided to synthesize and study the optoelectronic properties of some indeno

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• ) complex with 1,3-dicyclohexylimidazol-2-ylidene is found to efficiently catalyze the borylation of arenes and heteroarenes. The resulting aminoborylated products can be converted to the corresponding boronic acid derivatives simply by treatment with suitable diols or diamines. Keywords: boronic acid; C–H

• instability of 11-B during isolation (Table 2, entry 8). Our protocol was able to borylate non-benzofused five-membered heteroarenes. Pyrrole 12 was much less reactive than indoles, and required neat conditions to obtain a modest yield of the borylated product 12-B (Table 2, entry 9). Thiophene (13) afforded

• a 1.1:1 mixture of 2-borylated and 2,5-diborylated products under our standard conditions (Table 2, entry 10). 2-Substituted thiophenes 14 and 15 and furan 16 were borylated successfully at the 5-positions (Table 2, entries 11–13). Electron-deficient heteroarenes such as pyridine and quinolone

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• cross-dehydrogenative coupling (CDC) reactions of alkanes, which were reported by Li and other groups [11][12][13][14][15]. Recently, several types of reactions with alkanes as substrates have been developed, such as the Minisci reaction with heteroarenes [16][17], radical addition to unsaturated bonds

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

• University, Chikusa, Nagoya 464-8602, Japan 10.3762/bjoc.11.295 Abstract Triaryl-2-pyridylidene effectively facilitates the gold-catalyzed oxidative C–H arylation of heteroarenes with arylsilanes as a unique electron-donating ligand on gold. The employment of the 2-pyridylidene ligand, which is one of the

• effect on the reaction progress (Table 1, entries 8 and 9). Nevertheless, the highest yield achieved by the use of AuCl(PyC) may be attributed to the highly electron-donating nature of the PyC ligand. Oxidative C–H arylation of heteroarenes with arylsilanes catalyzed by AuCl(PyC) Having discovered the

• positive effect of using PyC as a ligand, we further examined the C–H arylation of various heteroarenes with arylsilanes (Table 2). It should be noted that all of the examined heteroarenes were not successfully applied in the previous gold-catalyzed C–H arylation. The reactions of 1a with halogenated

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• sulfonimidation [55]. In contrast to the direct transformation of the weakly acidic C–H bonds in these electron deficient arenens/heteroarenes, the amidation of normal aryl C–H bonds usually relied on the presence of a directing group (DG). In 2010, Li et al. [56] reported the o-amidation of 2-arylpyridines 34

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• , Vishwakarma et al. [56] developed a catalytic approach for the halogenation of phenols and heteroarenes by using reusable Cu-Mn spinel oxide as catalyst. By employing NXS as halogen source, the Cu-Mu spinel oxide was able to catalyze the halogenation of phenols 40 to give either para-halogenated or ortho

• biological functions of halogenated heteroarenes [57], the synthesis of haloheteroarenes via the corresponding arene C–H halogenations also gained extensive attention. In 2009, Pike and co-workers [58] reported the synthesis of halogenated 1,3-thiazoles using copper(II) halide as a catalyst. As shown in

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

• . Palladium-catalyzed desulfitative arylation of heteroarenes allowed in a first step the synthesis of fluoroaryl-heteroarene units in high yields. Then, the next steps involve direct arylation with aryl bromides catalyzed by PdCl(C3H5)(dppb) to afford triad or tetrad heteroaromatic compounds via

• involved in palladium-catalyzed direct arylations with a set of heteroarenes (e.g., thiophenes, thiazoles, furans). Then, the resulting heteroarylated polyfluorobenzenes were arylated using PdCl(C3H5)(dppb) catalyst in the presence of KOAc as the base in DMA at 150 °C using a wide range of aryl bromides as

• pathway for fluorinated π-conjugated oligomers (i.e., dyads, triads, and tetrads). This novel strategy involves only palladium-catalyzed iterative C–H bond arylations. In a first step, PdCl2(CH3CN)2-catalyzed desulfitative regioselective arylations of heteroarenes using fluorinated benzenesulfonyl

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• Selectfluor/KBr [13], and the thiocyanation of representative heteroarenes and ketones with NH4SCN [14][15]. Oxidative transformations such as amide to imide mediated by Selectfluor in combination with CuBr have also been shown [16][17]. In an earlier study, we reported on the potential of Selectfluor to act

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported. Keywords: indolizine; nitrogen heterocycles; N-ylide; 4-pyridylpyrimidine; pyrrolo[1,2-c]pyrimidine; Introduction Two heteroarenes linked through a single bond [1] proved to be versatile

• structural motifs for a broad range of compounds with applications as advanced fluorescent materials [2][3], ligands [4][5], bioactive compounds [6], and for the design of dynamic chemical devices [7][8][9][10]. The most accessible route to hybrid heteroarenes is the direct coupling [1][11][12]. However, in

• some cases alternative routes could be useful to achieve structural variety [13]. An alternative route is to start from accessible simple heteroarenes linked by a single bond and to transform one of them or both into more complex structures [14][15]. Nitrogen-containing compounds from the class of

Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives

• Fatma Belkessam,
• Aidene Mohand,
• Jean-François Soulé,
• Abdelhamid Elias and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 2912–2919, doi:10.3762/bjoc.10.309

• –2 mol % palladium catalysts, the target 2,5-diheteroarylated thiophenes were obtained in moderate to good yields and with a wide variety of heteroarenes such as thiazoles, thiophenes, furans, pyrroles, pyrazoles or isoxazoles. Moreover, sequential heteroarylation reactions allow the access to 2,5

• -diheteroarylated thiophenes bearing two different heteroaryl units. Keywords: aryl halides; catalysis; C–H bond activation; direct arylation; heteroarenes; palladium; Introduction 2,2':5',2"-Terthiophene (or 2,5-di(2-thienyl)thiophene) (Figure 1) and many of its derivatives are important structures due to their

• than other Pd-catalyzed cross-coupling reactions as it avoids the preparation of an organometallic derivative and also as the major byproducts of the reaction are not metallic salts but a base associated to HX. The metal-catalyzed direct arylation of a wide variety of heteroarenes using aryl halides as

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

• ) acetate as additives proved essential for achieving high yields of the desired trifluoromethylated arenes. 2-Arylpyridines, but also other aryl-substituted heteroarenes were successfully trifluoromethylated with complete regioselectivity in the position ortho to the aryl–heteroaryl bond, with moderate to

• and F.-L. Qing, where catalytic copper was used in the trifluoromethylation of sp2-C–H bonds by a nucleophilic CF3-releasing reagent [91]. In this paper, heteroarenes or arenes bearing acidic sp2-C–H bonds were trifluoromethylated by the Ruppert–Prakash reagent in presence of catalytic copper(II), a

• -subsituted alkenes were sometimes obtained along with the desired addition products (Scheme 9). Afterwards, N. Kamigata et al. applied this system to arenes [99] and heteroarenes (furans, pyrroles and thiophenes) [102][103][104] and gave a full account of this work (Scheme 9) [101]. Monosubstituted benzenes

AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldoximes with α,β-unsaturated carbonyl compounds

• Qiuping Ding,
• Dan Wang,
• Puying Luo,
• Meiling Liu,
• Shouzhi Pu and
• Liyun Zhou

Beilstein J. Org. Chem. 2013, 9, 1949–1956, doi:10.3762/bjoc.9.231

• processes. Isoquinoline derivatives, an important class of nitrogen-containing polycyclic heteroarenes, have attracted considerable attention because of their pharmacological activities, including antitumor, antifungal, antimalarial, antihypertensive and antihistaminic activity, and their photo- and

Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

• Jungho Jun,
• Hyu-Suk Yeom,
• Jun-Hyun An and
• Seunghoon Shin

Beilstein J. Org. Chem. 2013, 9, 1724–1729, doi:10.3762/bjoc.9.198

• the scarcity of such examples [2][3][4][5]. Earlier examples in this vein include intermolecular reactions of electron-rich arenes and heteroarenes [2][3]. More recently, relatively polarized 1,1-disubstituted olefins were also found to react intermolecularly with phenylacetylenes or propiolic acids

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• to benzene with a rate constant of 3.8 × 102 M−1 s−1 at 79 °C. In this study it was also demonstrated that the rate constants for addition reactions to electron deficient (protonated) heteroarenes can be much higher due to polar effects. Despite these insightful investigations a more general picture

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• research initiated spiralling interest by synthetic chemists in iminyl radical-mediated preparations. Recently iminyls have been generated from quite a variety of precursors [10][11][12][13][14][15], and their cyclisations onto arenes [16][17][18][19][20][21] and heteroarenes [22][23][24] have attracted

• derivatives of oximes with various aromatic and heteroaromatic architectures (Figure 1). Compounds 1a–f contain comparatively rigid arms and their aromatic acceptors range from electron-withdrawing to electron-releasing in character. In compounds 2a,b and 3 heteroarenes replace the benzene rings and in 4 the

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

• ; 2H-pyran-2-one; Introduction 6-Aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles have emerged as versatile synthons for the construction of an array of arenes and heteroarenes through base-induced ring transformation by nitrogen, sulfur and carbon nucleophiles [1]. However, suitably functionalized 2H