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

• challenging than those of aryl–aryl derivatives. These difficulties resulted from the special properties of thiopheneboronic acids – the sensitivity to polar reaction media and easy degradation by protodeboronation [53]. As a recent example of a metal-free synthesis of the targeted thienylpyridines (Figure 2A

• yielding [57][62]. Thus, a new mild synthetic route for the synthesis of 5-(pyridyl)thiophenes is required. We therefore investigated the synthesis of thienylpyridines using a metal-free approach. Results and Discussion At first, our efforts focused on the intramolecular cyclization reactions with mild

• ], 4 [11][12], 5 [33][34], 6 [35][36][37][38]. Metal-free synthesis of thiophene-based heterocycles (A) [54][55], (B) [56]. X-ray crystal structures of 8ad and 8an [68]. The proposed structure of sulfur ylide-like intermediates; resonance contributors (mesomeric structures) [69][70][71][72][78]. One

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

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

• photocatalysts, metal-free methods also have made tremendous advance. For trifluoromethylation of prefunctionalized substrates, these developments have expanded the substrate scope and provided milder conditions, but this field still suffered from limited and expensive trifluoromethylation reagents. Moreover

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

• method tolerates the presence of pyridine derivatives, alcohols, esters, carboxylic acids, Boc-protected amines, boronic pinacol esters and was applied to the late-stage functionalization of complex molecules. In 2016, the first metal-free photoredox-catalyzed radical thiol–yne reaction was reported by

• metal-free method for the synthesis of benzothiophenes via a photocatalyzed tandem addition/cyclization reaction (Scheme 11) [41]. Aryl thiols were coupled with dimethyl acetylenedicarboxylate, applying 9-mesityl-10-methylacridinium perchlorate (Acr+-Mes ClO4−) as organic photocatalyst and benzoic acid

• radical. Yadav and co-workers presented a metal-free radical thiol–ene approach, using benzophenone as photoredox catalyst (Scheme 13) [43]. No sacrificial oxidant is required for this reaction as benzophenone is regenerated by hydrogen atom transfer to the anti-Markovnikov radical intermediate. Aliphatic

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

• -workers thereafter reported that the trifluoromethylation of (hetero)arenes could also be performed under heterogeneous catalysis [33]. To this aim, the Ru- or Ir-based catalysts were replaced with a mesoporous graphitic carbon nitride polymer (mpg-CN), which offers the advantage of being cheap, metal

• -free and recyclable. A variety of heteroarenes, like pyrroles, oxazoles, furanes, thiophenes, indoles and pyrazines were successfully converted into the corresponding trifluoromethylated products in moderate to good yields (Scheme 27). Remarkably, a side chlorination reaction was observed during the

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

• -workers reported a metal-free protocol for the trifluoromethylation of styrenes with CF3SO2Na, tert-butyl hydroperoxide and benzoquinone (BQ) as oxidant. The reactions were run at 80 °C for 16 h to give mixtures of α-trifluoromethyl ketones 12 and the corresponding alcohols 13 (Scheme 6) [25]. The scope

• metal catalysts and/or a large excess of organic oxidants can be obstacles to production. In a quest for ideal conditions, Lei and co-workers exposed heteroatom-functionalised alkenes 14 to aerobic Cvinyl–heteroatom bond oxygenation under metal-free conditions, where oxygen from air worked in concert

• Scheme 10. β-Trifluoromethyl ketones could also be obtained from allylic alcohols 25 by a cascade trifluoromethylation/1,2-aryl migration. Yang, Xia and co-workers employed sodium triflinate under metal-free conditions with ammonium persulfate as the oxidant that was necessary to generate the CF3 radical

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• -efficient protocols, we have employed transition-metal-free approaches for the one-pot synthesis of imidazo[1,2-a]pyridines and thiazolamines by coupling β-ketoesters or their derivatives, phenylacetones and phenylacetophenones, with aminopyridines [20][21] and thioureas [22]. The strategy involves in situ

• the benzo[d]imidazo[2,1-b]thiazole derivatives via coupling of 2-aminobenzothiazole with the brominated β-ketoesters and amides. Over the past decade, there has been a lot of interest in KOt-Bu-mediated synthesis, especially after Itami’s group showed that KOt-Bu provides a metal-free approach to the

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

Beilstein J. Org. Chem. 2017, 13, 2671–2681, doi:10.3762/bjoc.13.265

• or a parallel-stranded duplex. The intrinsic stability of the metal-free duplex, its sequence and the method used to enforce a parallel orientation of the complementary strands play important roles, too. This becomes evident for example for the XPC–Ag(I)2–YPC base pairs, which were found to be more

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• . Review Properties of trifluoroethoxy-substituted phthalocyanines Research on TFEO-Pc has taken place since the 1990s [42]. The early stages of this research focused on spectroscopic investigations of metal-free phthalocyanine and its zinc complex which showed the most fundamental spectroscopic properties

• strong, and the Stokes shift is small, about 10 nm. On the other hand, metal-free trifluoroethoxy-substituted phthalocyanine (TFEO-H2Pc) shows a split in the Q band due to its low symmetry [47]. In metal-free phthalocyanine, the four pyrrole units in the center of the macrocycle have two protons

• . Therefore, metal-free phthalocyanine has the ability to donate and accept protons [48][49][50]. The protonation/deprotonation of the nitrogen atom in phthalocyanines easily modifies its chemical and electronic properties. And this protonation/deprotonation phenomenon is expected to be applied to chemical

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• dioxygenation [10][11], dihydroxylation [10][12], bisperoxidation [13], oxyamidation [14], aminohydroxylation [15], oxyphosphorylation [16], deamination [17] and carbonylation–peroxidation [18]. Several very recent reports have pertained to metal-free catalysts for difunctionalization of alkenes such as UV

• methods to construct peroxides are still highly desirable and valuable, and highly regioselective and efficient syntheses of peroxides with structural control are still difficult to achieve. Herein, we report a metal-free iodination–peroxidation reaction for the direct vicinal difunctionalization of

• product 2a. Conclusion In summary, we have established a metal-free process at room temperature for the direct vicinal difunctionalization of alkenes with iodine and TBHP to synthesize 1-(tert-butylperoxy)-2-iodoethanes. This procedure is a simple and high-yielding method with excellent regioselectivity

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• chromones via domino chromone ring construction and C(sp2)–H bond sulfenylation have been achieved under transition-metal-free conditions by using KIO3 as the only catalyst. Keywords: C–H sulfenylation; chromones; domino reaction; free-radical; transition-metal-free; Introduction The C–S bond-forming

• transition-metal-free oxidative coupling has emerged as a powerful complementary tactic in C(sp2)–S bond forming reactions [16][17][18][19][20][21][22][23][24][25][26][27]. As a beneficial and sustainable approach, such transition-metal-free cross coupling transformations have been successfully employed in

• readily synthesized with several different transition-metal-free C–H cross-coupling approaches. Zhou and co-workers reported the NH4I-promoted synthesis of 3-sulfenylated chromones via the direct chromone C–H sulfenylation by using different sulfur sources (A, Scheme 1) [38][39]. Recently, our continuous

Solvent-free and room temperature synthesis of 3-arylquinolines from different anilines and styrene oxide in the presence of Al₂O₃/MeSO₃H

• Hashem Sharghi,
• Mahdi Aberi,
• Mohsen Khataminejad and
• Pezhman Shiri

Beilstein J. Org. Chem. 2017, 13, 1977–1981, doi:10.3762/bjoc.13.193

• ]. Transition metal-catalyzed processes [5][6][7][8] and metal-free paths [9][10][11] are two general approaches for the synthesis of this type of compounds. However, the existing methods suffer from complicated multistep processes, limited availability of substrates, toxic organic solvents, long reaction times

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

• . Mal and co-workers reported a metal free, solvent-free and room temperature synthesis of amide bonds at 62–75% yield under ball-milling (21 Hz) from aromatic aldehydes and N-chloramine in presence of 20 mol % of tetrabutylammonium iodide (TBAI) and 2.0 equiv of TBHP (Scheme 16) [79]. Aromatic

• ). However, NCS-cericammonium nitrate (CAN) successfully yielded mono-chlorinated products [88]. Consecutively, the same group reported metal-free oxidative iodination of electron rich aromatic rings with molecular iodine and oxone (Scheme 25) [98]. This method proved to be highly chemoselective and no

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• proceeds via base-promoted propargyl–allenyl rearrangement followed by cyclization and allyl migration. Phosphine-substituted indoles can be synthesized by a similar strategy. Keywords: allyl migration; benzothiophene; indole; metal-free; propargyl-allenyl; Introduction Heterocycles are frequently found

• (Figure 1) [7][8][9]. Moreover, benzothiophenes have extensive applications in materials science. Besides the traditional methods of transition metal-catalyzed cyclization of alkyne substrates [10][11][12], the synthesis of benzothiophenes via metal-free conditions has recently aroused much attention [13

• -pot process. Based on our understanding of organosulfur chemistry [20][21][22], we report herein a simple, metal-free method for the formation of benzothiophenes using an intramolecular addition of a sulfur atom (originated from a sulfide) to the electron-deficient allene moiety generated in situ by a

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

• promoting the reaction at room temperature (Scheme 5). Transition metal-free approaches for oxidative dehydrogenation Apart from IBX, various other oxidants (non-metallic) have been applied for oxidative dehydrogenation of C–C and C–N bonds. The synthesis of heteroaromatic compounds such as quinazolinones

• reacted with o-aminobenzylamine and substituted o-aminobenzylamines to provide the desired products in decent yields (Scheme 8b). Kumar et al. demonstrated transition metal-free α-C(sp3)–H bond functionalization of amines via an oxidative cross-dehydrogenative coupling reaction [44]. They reported a one

• dehydrogenation Metal-free organocatalytic aerobic oxidative dehydrogenation of heterocycles is another atom economical and green strategy of accessing various heteroaromatics. Not very many reports are present in the literature to demonstrate this. Hence, the available few render special attention. One such

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• reported intriguing 1,3-proton shift of 4,4,4-trifluorobut-2-yn-1-ols was successfully extended to the 4,4,4-trifluorobut-2-en-1-ol system under metal-free conditions to afford the corresponding saturated ketones in high to excellent chemical yields using such a convenient and easy-to-handle base as DBU at

• work is considered to draw a clear line with these instances because of the apparently convenient metal-free process. Moreover, the same type of proton shift has also reported by two groups. For example, during the reaction of (E)-2-(trifluoromethyl)vinylsilane and benzaldehyde in the presence of an

• tractable tertiary amine as DBU, thus under metal-free conditions like the cases of the Ando [14] and Martín-Matute groups [15]. Moreover, this intriguing proton shift was clarified to be applied for optically active allylic alcohols whose chirality was transmitted almost in a perfect fashion. These results

Mechanochemistry-assisted synthesis of hierarchical porous carbons applied as supercapacitors

• Desirée Leistenschneider,
• Nicolas Jäckel,
• Felix Hippauf,
• Volker Presser and
• Lars Borchardt

Beilstein J. Org. Chem. 2017, 13, 1332–1341, doi:10.3762/bjoc.13.130

• ) isopropoxide, and acts as porogen in further syntheses. Infrared spectra of the monomers ethylene glycol (EG, blue) and citric acid (CA, green blue), the metal-free polymer achieved by 5 min ball milling with ZrO2 balls (d = 15 mm) (EG-CA, dark blue) and the polymeric precursor after adding titanium(IV

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• Liquan Tan Cui Chen Weibing Liu College of Chemical Engineering, Guangdong University of Petrochemical Technology, 2 Guandu Road, Maoming 525000, P. R. China. Fax: +86-668-2923575; Tel: +86-668-2923444 10.3762/bjoc.13.107 Abstract We present a metal-free method for α-acetoxyarone synthesis by

• was limited to α-substituted aryl ketones, and acetophenones were unsuitable for this conversion. In addition, this method requires harsh catalytic conditions, using scarce iron and copper complexes. The development of novel metal-free methods for the preparation of α-acetoxyaryl ketones is therefore

• an attractive target for organic chemists. Simple, inexpensive, and metal-free methods [14][15], involving safe and clean oxidation procedures, need to be developed. Here, we report a metal-free, novel, and efficient self-intermolecular oxidative coupling procedure for the synthesis of α-acetoxyaryl

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• polyfunctional reagents in Ugi-4CR opens ways to different post-cyclization reactions, thereby broadening the scope. Thus the Ugi-4CR involving substituted propiolic acids, can be followed by electrophilic ipso-iodocyclization [62] or transition-metal-initiated [63][64][65][66][67][68] and metal-free

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

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

• metals Pt [28], Au [29], Ru [30], Rh [31][32][33], Ni [34], Pd [35], and Pd/Ag [36]. However, a metal-free hydroarylation variant of C=C bonds under the action of Brønsted or Lewis superacids has been developed [37][38] and we were able to extend the scope of this reaction [24][25]. The expected reaction

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• -2-ylamides 54 in good yields (Scheme 16a). The mechanism for this cyclization as proposed by the authors is depicted in Scheme 16b [98]. Following this work, the Čikotienė group studied the metal-free halogen, chalcogen, or oxocarbenium ion-mediated cyclization of a series of N-propargylthioureas 55

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• Sharpless asymmetric dihydroxylation as the sole source of chirality [27]. For the synthesis of chroman derivative 2, first a base-mediated intramolecular SNAr reaction was envisioned for the aryl C–O bond formation under transition-metal-free conditions [28][29][30]. The additional benefit of this strategy

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• '. Therefore, the development of a metal-free and straightforward greener protocol for the preparation of propargylamine is highly desirable. A schematic presentation of various metal-catalyzed protocols including the present work is outlined in Scheme 2. Results and Discussion In connection with our interest

• . Although we are not sure about the exact routes to the formation of 3, other results indirectly corroborate the proposition. For example, the inability of the o-methoxybenzaldehyde, p-hydroxybenzaldehyde and o–hydroxyacetophenone to undergo a similar reaction under metal−free conditions could be explained

• unusual but added role of the hydroxy group of salicylaldehyde, which paves the way to develop metal-free as well as solvent-free A3 coupling reactions leading to the formation of propargylamine – the useful synthetic intermediate and an important unit of many bio-active compounds. The reaction conditions

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• reported a metal-free photocatalytic aerobic oxidation of thiols to disulfides under continuous-flow conditions [64]. Disulfides are useful molecules employed as drugs, anti-oxidants or pesticides as well as rubber vulcanizating agents [65]. Symmetric disulfides are generally obtained by oxidative coupling

• Ar–Csp3, Ar–Csp2 and Ar–Csp bond-forming reactions. The use of a photochemical flow reactor, consisting of a polyfluorinated tube reactor wrapped around a 500 W Hg lamp, allowed to overcome batch limitations paving the way for metal-free arylation reactions via phenyl cations. Derivatives 14a–g were