Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• with electron-rich as well as electron-poor arenes and heteroarenes. Subsequently, in order to prove the practicability of this approach, 1,2,3-triazoles were assembled by reaction of 157 with alkynes. In 2019, Bosque and Bach [41] reported that 3-acetoxyquinuclidine (q-OAc) could be utilized as an

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• bond alkynylations of heteroarenes [9]. The 1,1-dichloro-1-alkenyl moiety is found in a number of pyrethroid insecticides including permethrin and marine natural products such as caracolamide A [10] (Figure 1). 1,1-Dichloro-1-alkenes 2 are commonly prepared from the corresponding aldehydes 1 in one

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• , Road, North Chicago, Illinois 60064, United States of America 10.3762/bjoc.16.111 Abstract The first example of photocatalytic trifluoromethoxylation of arenes and heteroarenes under continuous-flow conditions is described. Application of continuous-flow microreactor technology allowed to reduce the

• methodologies [27][28][29][30][31], herein we report the first application of flow methods for the direct trifluoromethoxylation of arenes and heteroarenes. Results and Discussion Among the three reagents shown in Scheme 1B, we decided to use the “second” Ngai reagent (1, Scheme 1C) for our investigation, as

• conditions in hands, we proceeded to investigate the trifluoromethoxylation of different arenes and heteroarenes in acetonitrile. Solvent mixtures and lower concentrations had to be used in some cases due to solubility issues. As can be seen in Scheme 3, trifluoromethoxylation occurs preferentially at the

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• radical adds to the imine substrate 5.5, yielding the desired amine product 5.6. Finally, the same group developed a photochemical radical alkylation of heteroarenes with alkyl trifluoroborate salts (Scheme 6) [51]. In this reaction, the photoinduced oxidative fragmentation of the alkyl trifluoroborate

• visible-light irradiation. The key aryl radical was trapped with heteroarenes, such as 11.2, to give the arylation products 11.3. Recently, similar methodologies for aryl radical generations have been developed exploiting flow techniques [74] and different organophotocatalysts, such as a metal-free

• for the synthesis of the arylated heteroarenes 12.3 via an intermolecular process [79]. Alemán and co-workers used PHTH (OD16) for the synthesis of various heteroatom-containing bicycles 12.4 through a tethered electrophile approach [80]. For the second strategy, König and co-workers developed an

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• )aryldiazonium salts, a panel of difluoromethylated arenes and heteroarenes was obtained (26 examples, up to 84% yield). Note that the transformation was also carried out starting from 4-methoxyaniline followed by the in situ formation of the corresponding diazonium salt. In the same vein, the authors used this

• organocopper derivative was then oxidized resulting in the formation of the desired products. Note that in 2018 the same group reported the copper-mediated oxidative difluoromethylation of heteroarenes under similar reaction conditions (TMSCF2H, CuCN, 9,10-phenanthrenequinone, t-BuOK in NMP) [46]. Not only

• oxazoles (17 examples, up to 87% yield) were difluoromethylated but a variety of other heteroarenes turned out to be suitable such as pyridine, imidazole, benzo[d]thiazole, benzo[b]thiophene, benzo[d]oxazole, thiazole and thiophene derivatives (Scheme 6). Copper-based CF2FG-containing reagents Besides the

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• reported a metal-free photoarylation of five-membered heteroarenes with aryldiazonium salts and meso-arylated porphyrin derivatives as photoredox catalyst [11]. Compounds such as furan, thiophene, and N-Boc-pyrrole derivatives were obtained by this methodology in 29–81% yields (Scheme 3). The key-step of

• , meta and para positions. Moreover, the methodology also showed effectiveness for heteroarenes such as pyridines and benzothiazoles. The authors also evaluated the use of NiTPP as a photoredox catalyst for other transformations involving both oxidative and reductive quenchings. The NiTPP-catalyzed

• ). For an oxidative quenching, the photoarylation of heteroarenes and alkynes with aryldiazonium salts, and the oxidative decarboxylative coupling between cinnamic acid and tetrahydrofuran also showed better results when NiTPP was used instead of eosin [32][33][34] (Scheme 10). Regarding protocols

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• ., formamide) and ethers through C–H activation using various five- and six-membered heteroarenes (e.g., benzothiazole) and employing benzaldehyde (8) as the photoinitiator [56]. This protocol was compatible with both C(sp3)–H activation (N-alkyl C–H bonds of amides or Cα–H bonds of ethers) and C(sp2)–H

• activation (carbonyl C–H bonds of formamides). Some of the amides or ethers found to be compatible with this method are shown in Scheme 26. A wide range of heteroarenes 114 was also found compatible with this method, including substituted benzothiazole substrates, substituted benzimidazoles, and thiazoles

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• diverse products via formation of C–C bonds. Nucleophiles as diverse as electron-rich arenes or heteroarenes [41][42], alkenes [43], allylmetalloids [44][45][46], enol derivatives [47][48], and organometallics [49] are suitable for the Nicholas reaction. Allenic byproducts are rarely seen, and

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• ) as an additive (Scheme 78). Mechanistic studies revealed that this reaction probably proceeds through a radical pathway. Copper-catalyzed trifluoromethylation of arenes and heteroarenes: In 2013, Xi et al. [142] reported a CuCl-catalyzed direct trifluoromethylation of sp2 C–H bonds with Togni reagent

• heteroarenes with the CF3 radical through a Cu(I/II) catalytic cycle. In 2013, the Szabó [143] and Wang group [144] described the copper-mediated C–H trifluoromethylation of quinones with Togni’s reagent. Szabó utilized a stoichiometric amount of CuCN combined with catalytic bis(pinacolato)diboron, whereas

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• functionalization of heteroarenes such as thiophenes, furans, pyrroles and indoles [14][15], this methodology has been widely applied for the preparation of new aryl-substituted heteroarenes [16][17][18][19][20][21]. Several results dealing with the C–H bond functionalization of indoles have been reported allowing

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• ][20][21][22][23]. These carbonyl-substituted heteroarenes possess basic sites (nitrogen or oxygen atoms of the heterocyclic system), which are fully protonated in acid, so that upon subsequent protonation of the carbonyl oxygen, more reactive dicationic electrophiles can be generated. Previously

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• high level of functional group compatibility, intramolecular alkylations, inter and intramolecular C–H bond activation and regio/stereoselective homocoupling of alkynes [71][72][73]. Group of Cho and Chang have unprecedentedly reported a Rh catalytic system for facile addition of heteroarenes to both

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• potassium hydroxide and DMSO. This novel protocol is featured by direct C–H mercaptalization of heteroarenes and a simple reaction system. Keywords: benzothiazole; benzoxazole; C–H functionalization; mercaptalization; 1,3-propanedithiol; Introduction Both 2-mercaptobenzothiazoles and 2

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• through the addition of radical 99 to the quinones 94. Finally, the intermediate 100 occurres reoxidation with Ag(II) to provide the final product 95 along with regenerated Ag(I). In 2015, Duan et al. developed a Ag(I)-catalyzed oxidative ring-opening of cyclopropanols 91 with heteroarenes 101 or 103 for

• the synthesis of carbonyl-containing alkyl-substituted heteroarenes 102 or 104 under mild conditions in moderate to good yields with good functional group tolerance (Scheme 22) [100]. This reaction went through a selective C(sp3)–C(sp3) bond cleavage, C–H activation and C(sp3)–C(sp2) bond formation

• cyclopropanols and vinyl azides. Ag(I)-catalyzed oxidative ring-opening of cyclopropanols with quinones. Ag(I)-catalyzed oxidative ring-opening of cyclopropanols with heteroarenes. Cu(I)-catalyzed oxidative ring-opening/trifluoromethylation of cyclopropanols. Cu(I)-catalyzed oxidative ring-opening and

Organometallic vs organic photoredox catalysts for photocuring reactions in the visible region

• Aude-Héloise Bonardi,
• Frédéric Dumur,
• Guillaume Noirbent,
• Jacques Lalevée and
• Didier Gigmes

Beilstein J. Org. Chem. 2018, 14, 3025–3046, doi:10.3762/bjoc.14.282

• . Parallel to this, 4CzIPN was also used as an organoredox catalyst for the alkylation of heteroarenes [85], the oxidation of silicates [86], the alkylation of imines [87], the α-arylation/heteroarylation of 2-trifluoroboratochromanones [88]. In these different situations, comparisons with reference

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• ]. Direct C(sp2)–H bond carboxylation As described above, C–H carboxylations with CO2, particularly C(sp2)–H carboxylation reactions, have attracted much research interest. As a consequence, Nolan [57] and Hou [58] independently reported Cu-catalyzed carboxylations using heteroarenes as substrates, which

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• result (64% NMR yield) was observed with 6.0 equiv of 3a in the presence of 30 mol % of Cu2O in DMF at 100 °C for 24 h (Table 2, entry 12) [38]. Using the optimal conditions for the reaction in entry 12, Table 2, various iodoarenes or -heteroarenes (3b–r) could be converted into the corresponding CF2CF2

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• of indoles. Co-catalyzed asymmetric hydroarylation of alkenes with indoles. Co-catalyzed hydroarylation of alkenes with heteroarenes. Co(III)-catalyzed hydroarylation of activated alkenes with 2-phenyl pyridines. Co(III)-catalyzed C–H alkylation of arenes. Co(III)-catalyzed C2-alkylation of indoles

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• heterocycle, and the benzene moiety can tolerate all manner of substituents in all positions, however, only mono-substituted systems are explored. This is a powerful procedure, which allows for the circumvention of traditional Pd or Cu catalysed couplings of heteroarenes, which are notoriously difficult. A

• , as well as aliphatic chains. Unsurprisingly, esters and other base labile groups are not encountered. A recent publication by König and his group shows the DDQ catalysed (3DDQ Ered*(cat/cat•−) ≈ +3.18 V vs SCE) C–H amination of arenes and heteroarenes using weakly nucleophilic species such as

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• , arenes and heteroarenes [43][44]. A first solution to value the 2-iodobenzoic moiety released from EBX has arisen from the reaction of derivatives 22 with N-(aryl)imines 23 in the presence of 10 mol % of Pd(OAc)2, which gives access to tri- or tetrasubstituted furans 24 and N-(aryl)formamides 25 (Scheme

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• heteroarenes was realized using the benziodoxolone hypervalent iodine reagents indoleBXs. Functionalization of the C–H bond in bipyridinones and quinoline N-oxides catalyzed by a rhodium complex allowed to incorporate indole rings into aza-heteroaromatic compounds. These new transformations displayed complete

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• TBAB [24][25][26][27]. However, for inert and liable to dehalogenation bromo-heteroarenes, no desired response had been obtained yet. Thus, this work was going to establish a mild and chemoselective olefination of 3-bromoindazoles under ball-milling conditions (Scheme 2). Results and Discussion

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

• 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

• benzamides were efficiently synthesized in 36–82% yields. Direct trifluoromethylation of C(sp2)–H with a nucleophilic trifluoromethylation reagent (TMSCF3): Previously, the radical and electrophilic trifluoromethylation of arenes and heteroarenes were often limited to substrates bearing electron-donating

• substituents and generate mixture of regioisomers in some cases. In 2012, the group of Qing [56] designed a copper-catalyzed oxidative trifluoromethylation of heteroarenes and electron-deficient arenes with TMSCF3 through direct C−H activation (Scheme 35). At first, the oxidative trifluoromethylation of 1,3,4

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