One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• compounds 7f and 7g, the low reactivity resulted from the decreased mesomeric effect of the furan structure: the higher electronegativity of oxygen facilitated the polarized form [71]. Among various arenes, the 4-nitrophenyl substituent 7p only afforded the desired thiophene 8p in a moderated yield (42

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• target functional groups. Recently, several examples of conversion of anilines into trifluoromethylated arenes, named Sandmeyer type trifluoromethylation, were disclosed. This protocol offered a complementary method for the synthesis of trifluoromethylated arenes from the corresponding aromatic amines

• . In 2013, Fu [43], Gooßen [44] and Wang [45] almost simultaneously reported Sandmeyer type trifluoromethylations. The group of Fu [43] accomplished a copper-mediated Sandmeyer trifluoromethylation reaction for the conversion of aromatic amines into trifluoromethylated arenes (Scheme 24). This reaction

• compound were based on the use of prefunctionalized substrates. Instead, the direct trifluoromethylation of C–H bonds of arenes and heteroarenes was a more efficient and ideal protocol due to its atom and step economy. However, the direct trifluoromethylation of C–H bonds was not simple. And only in recent

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• , the unsatisfactory separation of 1-methylisoquinoline intermediate 4 from its unmethylated precursor 3 rendered this protocol unattractive. This is a problem that is common to numerous methylation protocols, including methylation of metalated arenes [16], methylation of arenes bearing directing groups

• alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline (1), but should also be of value for the synthesis of other 1-methylisoquinolines. We could demonstrate that the aminomethylation of metalated arenes with Eschenmoser’s salt followed by hydrogenolytic cleavage is a highly attractive alternative to direct

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• the preparation of sulfoxides was recently reported by our laboratory (Scheme 49) [86]. Sulfinamides were applied as sulfinylation reagents for a diversified scope of arenes and heteroarenes with ammonium persulfate ((NH4)2S2O8) as oxidant under irradiation with visible light. Although none of the

• arenes react well and substituted pyrroles and indoles give the corresponding sulfoxides in high yields. Less electron-rich thiophene or benzene derivatives gave low yields. Nevertheless, carbocyclic azulene afforded the respective sulfoxide in 88% yield. We propose an electrophilic aromatic substitution

• two arenes with different nucleophilicity, which were reacted with one sulfinamide. The respective product with the stronger nucleophile is formed exclusively. In reactions with two arenes having similar nucleophilicity a mixture of the respective products was obtained. Sulfonyl halides and

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

• example of such transformation was reported in 1990 by Kamigata and co-workers, and described the introduction of the CF3 moiety onto arenes in the presence of a catalytic amount of RuCl2(PPh3)3 (Scheme 24) [6][7]. This reaction, however, suffered from limitations, such as its poor regioselectivity in the

• case of monosubstituted arenes, and its incompatibility with aromatics bearing strong electron-withdrawing groups. The authors proposed the mechanism represented in Scheme 24. A redox-transfer reaction occurred between CF3SO2Cl and the Ru(II) catalyst producing radical anion 30, which then furnished

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

• -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

• O2 as the terminal oxidant. This method allowed the trifluoromethylation of arenes bearing electron-donating as well as electron-withdrawing groups in moderate to good yields (Scheme 41) [64]. It has to be noted that bis-CF3 products as well as regioisomers were also characterised or detected in

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• : calix[4]resorcinarene; host–guest complexes; p-nitroanilines; polarimetry; supramolecular chemistry; Introduction During the last decades calix[n]arenes and calix[n]resorcinarenes (CAs) have emerged as versatile supramolecular host systems for various applications [1][2][3][4][5], spanning from sensors

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• chronological order, focusing first on arenes with one Rfn substituent. As shown in Scheme 5 (top), the commercially available meta diiodide 1,3-C6H4I2 was treated with copper (1.0 equiv) and Rf6I (0.5 equiv; a deficiency to help suppress dialkylation) in DMSO at 110 °C. Similar recipes have previously been

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

• NSA14 to electron-rich arenes. Addition of nitrosoalkenes NSA14 to pyrroles and indoles. Reaction of phosphinyl nitrosoalkenes NSA15 with indole. Reaction of pyrrole with α,α’-dihalooximes 70. Synthesis of indole-derived psammaplin A analogue 72. Synthesis of tryptophanes by reduction of

p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• Alena A. Vavilova Ivan I. Stoikov Kazan Federal University, Kremlevskaya, 18, Kazan 420008, Russian Federation 10.3762/bjoc.13.188 Abstract New p-tert-butylthiacalix[4]arenes, which are mono-, 1,2-di- and tetrasubstituted at the lower rim containing N-(4’-nitrophenyl)acetamide and N,N

• receptors for F−, CH3CO2− and H2PO4− ions, which based on the synthesized thiacalix[4]arenes, have been obtained. It was shown that p-tert-butylthiacalix[4]arene tetrasubstituted at the lower rim by N-(4’-nitrophenyl)acetamide moieties bonded to the anions studied with association constants within the range

• ,N-diethylacetamide fragment and its further functionalization with the N-(4’-nitrophenyl)acetamide moiety. We also calculated the proposed model of anion binding for the new and previously synthesized thiacalix[4]arenes and compared their complexation properties toward number of singly charged

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• benzylic iodination could be observed in case of alkyl benzenes. Interestingly, benzaldehyde derivatives did not lead to any over-oxidation to acids in presence of oxone. Trihaloisocyanuric acids are also used effectively for halogenations of arenes and 1,3-dicarbonyl compounds and double bond-containing

• systems [99]. Moorthy and co-workers investigated the potential of tribromoisocyanuric acid (TBCA) and trichloroisocyanuric acid (TCCA) under a solvent-free mechanomilling system for halogenations of electron rich arenes. The reactions were found to have yields above 80% for most of the cases but with

• reaction of electron-rich arenes [88][98]. Mechanochemical aryl halogenation reaction using trihaloisocyanuric acids [100]. Mechanochemical fluorination reaction by LAG method [102]. Mechanochemical Ugi reaction [116]. Mechanochemical Passerine reaction [116]. Mechanochemical synthesis of α-aminonitriles

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

• that enables such transformation requires special mention. Herein we indicate such an elegant report where o-aminobenzamide 43 were reacted with various methyl(hetero)arenes in the presence of di-tert-butyl peroxide (DTBP, 0.9 mmol), p-toluenesulfonic acid (0.6 mmol) in DMSO at 110 °C for ≈20 hours to

• facilitate a variety of quinazolinones 44 (Scheme 12) [47]. N-Alkyl benzamides 44´ were also synthesized with this protocol. The average yield ranged from 30 to 92%. Other than methyl(hetero)arenes dimethylamides were also used as C-synthon for such intermolecular annulation to afford unsubstituted

• -mediated oxidative dehydrogenation. NBS-mediated oxidative dehydrogenation of tetrahydro-β-carbolines. One-pot synthesis of various methyl(hetero)arenes from o-aminobenzamide in presence of di-tert-butyl peroxide (DTBP). Oxidative dehydrogenation of 1, 4-DHPs. Synthesis of quinazolines in the presence of

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• reaction conditions. As an alternative reagent for the acylation of arenes with esters Eaton’s reagent (phosphorus pentoxide, 7.7 wt % in methanesulfonic acid) has been described in the literature [28][29]. Eaton’s reagent has advantages over polyphosphoric acid as it is an easy to handle, non-viscous and

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• arenes can be markedly facilitated using 1-imidoalkylphosphonium salts derived from triarylphosphines with electron-withdrawing substituents such as tris(m-chorophenyl)phosphine, tris(p-chlorophenyl)phosphine and tris[p-(trifluoromethyl)phenyl]phosphine. Microwave irradiation also considerably

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• of the mannosyl donor in three steps and 46% overall yield [64]. 3.4.2 Stereospecific Pd-catalyzed glycosylation: In 2016, Walczak and colleagues [65] described the Pd-catalyzed glycosylation of arenes using anomeric stannanes as donors and aryl halides as the acceptors. The reaction appears to be

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• University, Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia Institute of Synthetic Rubber, Gapsalskaya str., 1, Saint Petersburg, 198035, Russia 10.3762/bjoc.13.89 Abstract The metal-free reaction of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles with arenes in neat triflic acid (TfOH, CF3SO3H

• investigation of their properties are of ongoing interest in chemistry and medicine. Based on our previous works on reactions of cinnamides [24] and 5-styryl-2H-tetrazoles [25] with arenes under superelectrophilic activation with Brønsted or Lewis superacids, we turned our attention towards the hydroarylation

• of the C=C double bond in 5-styryl-substituted oxadiazoles, such as (E)-5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles 1 (Scheme 1). The main goals of the current work were to investigate the reactions of oxadiazoles 1 with different arenes under the conditions of superelectrophilic activation and to

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

• halides have been extensively studied as substrates for the synthesis of phenols and aryl thiols. In very recent years, C–H activation represents a powerful strategy for the construction of functionalized phenols directly from various arenes. However, the synthesis of aryl thiols through C–H activation

• allows an access to functionalized products from simple arenes, avoiding their pre-functionalization [8][9][10]. The synthesis of phenols has greatly benefited from C–H activation, but the application in the synthesis of aryl thiols is still yet to be reported. Both phenols and aryl thiols have similar

• methods for the synthesis of these two important classes of compounds. Herein, we review the recent developments on transition-metal-catalyzed syntheses of phenols from aryl halides and arenes, and aryl thiols from aryl halides. Review 1 Transition-metal-catalyzed synthesis of phenols In early times

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• . Fluoroorganic compounds play a significant role as very effective therapeutics, and for this reason, Prakash, Olah et al. synthesized in 2010 trifluoromethyl-substituted arylpropanoic acids 12, 1-indanones 13 and dihydrocoumarins 14 (Scheme 5) [17]. These products have been obtained by utilizing arenes/phenols

Correction: Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2017, 13, 347–347, doi:10.3762/bjoc.13.38

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• the absorption maximum with increasing solvent polarity (CH3CN: 457 nm, MeOH: 432 nm, H2O: 415 nm). The prototropic equilibrium between 2 and 2cB is significantly shifted to the deprotonated form 2cB in the excited state, as commonly observed for hydroxy-substituted arenes. As a result, the pKa* of 2

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

• (Figure 1) have been utilized to enhance the electrophilicity of organic molecules. Recent spectroscopic and computational studies provided evidence that arenes might form strong hydrogen bonds between aryl C–H groups and anions (Cl−, NO3−, ClO4−, etc.) in the gas phase [28]. In addition, the introduction

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• ) intermediate may be well-stabilized by boron as a Z-type ligand, and the mesityl groups surrounding boron may favor the association of arenes for the deprotonation–metalation and the oxidative addition steps. Wang et al. proposed concerted metalation–deprotonation via a sigma bond metathesis involving a cyclic

TBHP-mediated highly efficient dehydrogenative cross-oxidative coupling of methylarenes with acetanilides

• Cui Chen,
• Weibing Liu and
• Peng Zhou

Beilstein J. Org. Chem. 2016, 12, 2250–2255, doi:10.3762/bjoc.12.217

• C–N bonds. Besides, this conversion is an important complement to the conventional C–N forming strategies. Keywords: dehydrogenative cross oxidative coupling; methyl arenes; N-arylbenzamides; TBHP; Introduction Recently, amides have attracted more and more attention due to their extensive

• , entries 2, 3, 5, and 9). To further extend the adaptability of this transformation, other methyl arenes were also checked under the standard conditions. Pleasingly, m-xylene and p-xylene afforded the desired product 3 successfully, but in lower yields (Table 2, entries 10 and 11). In the same manner, we

Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

• Dmitry S. Ryabukhin,
• Dmitry N. Zakusilo,
• Mikhail O. Kompanets,
• Anton A.Tarakanov,
• Irina A. Boyarskaya,
• Tatiana O. Artamonova,
• Mikhail A. Khohodorkovskiy,
• Iosyp O. Opeida and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 2125–2135, doi:10.3762/bjoc.12.202

• Minerals, L.M. Litvinenko Institute of Physical Organic and Coal Chemistry of NASU, Naukova St., 3a, Lviv, 79053, Ukraine 10.3762/bjoc.12.202 Abstract The reaction of 5-hydroxymethylfurfural (5-HMF) with arenes in superacidic trifluoromethanesulfonic acid (triflic acid, TfOH) as the solvent at room

• pressure tubes at 130 °C for 1 h result in the formation of only 5-arylmethylfurfurals (yields of 45–79%). 2,5-Diformylfuran (2,5-DFF) in the reaction with arenes under the action of AlBr3 at room temperature for 1 h leads to 5-(diarylmethyl)furfurals (yields of 51–90%). The reactive protonated species of

• strong Lewis acids (AlX3, X = Cl, Br) by their coordination with basic centers of organic compounds, or with acidic zeolites, possessing both Brønsted and Lewis acidity [33]. The main goal of this work was a study of reactions of 5-HMF and 2,5-DFF with arenes under electrophilic activation with Brønsted

Cp₂TiCl/D₂O/Mn, a formidable reagent for the deuteration of organic compounds

• Antonio Rosales and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2016, 12, 1585–1589, doi:10.3762/bjoc.12.154

• C–H bonds [8][9]. More recently, organometallic catalysts have been used in the development of methods for deuteration of organic compounds. In this sense, it has been reported that iridium complexes can catalyse the H/D exchange of arenes, cyclic alkenes and vinyl groups [10][11][12]. Ruthenium

• complexes catalyse α-deuteration of amines and alcohols [13] and palladium complexes catalyse the ortho-selective deuteration of arenes [14]. Also, SmI2/D2O-mediated the chemoselective synthesis of α,α-dideuterio alcohols directly from carboxylic acid under single-electron-transfer conditions [15]. However