Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• -workers reported a one-pot synthesis of substituted anthracenes 37 from o-tolualdehyde 34 and aryl iodides 35 via a palladium-catalyzed C–H arylation with a silver oxidant (Scheme 8) [42]. During optimization studies, the authors noted that steric and electronic effects strongly affected the cyclization

• –d). The authors also employed aliphatic alkynes in this methodology, but they obtained lower yields [60]. In a study published in 2011, Kakiuchi and co-workers reported a new method to synthesize dibenzo[a,h]anthracenes and picene derivatives by a ruthenium-catalyzed regioselective C–H arylation of

• ] cyclotrimerization reactions with bis(trimethylsilyl)acetylene (23). [2 + 2 + 2] Alkyne-cyclotrimerization reactions catalyzed by a CoCl2·6H2O/Zn reagent. Pd(II)-catalyzed sp3 C–H alkenylation of diphenyl carboxylic acids with acrylates. Pd(II)-catalyzed sp3 C–H arylation with o-tolualdehydes and aryl iodides

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• are crucial. In 2018, Ackermann and co-workers described a novel room temperature C–H arylation by using a continuous visible light photo-flow technique, allied with a manganese photocatalyst CpMn(CO)3 [142]. The new flow protocol enabled the synthesis of several arene- and heterocyclic-based

• amiodarone (93, antiarrhythmic activity) (Scheme 32A) [166]. The method consists of a tandem, regioselective Fe(III)-catalyzed C–H halogenation, followed by an Fe or Cu-catalyzed O-arylation to access the benzo[b]furan derivatives in high yields. Several natural products and pharmacologically active targets

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• reductive elimination occurs in the presence of base to achieve the desired product 119 (Scheme 36) [59]. Direct arylation of disubstituted triazoles 123 with aryl halides 124 using a Pd/C catalyst under solvent-free conditions to give fully decorated triazoles 125 was reported by Farinola et al. Different

• synthesis of fully decorated 1,2,3-triazoles 162, 164, and 166 was reported by Ackermann et al. via intramolecular oxidative C–H arylation of 1,2,3-triazoles 161, 163, and 165 using a reusable palladium catalyst in PEG, Pd@PEG, under O2 atmosphere. The main advantages of this strategy include i) a versatile

• ]triazoles 166 were also prepared through the cyclodehydrogenative arylation of 165. It was demonstrated that the Pd and PEG mixture could be reused for further cycles, and only a catalytic amount of the copper source, pivalic acid, and the substrates needed to be added [65]. As shown in Scheme 44, this

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

•  27). Recently, Vanderwal developed an oxidative cobalt-catalyzed olefin hydroalkylation/arylation cascade in which, instead of an EWG olefin as a terminator of the radical cascade, an aryl moiety served to this goal to generate a stabilized aryl radical that was further oxidized by an external

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• having no additional radical-sensitive substituents. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at room temperature. The selectivity control of intramolecular arylation was achieved by replacing the halogen: the use of 1-(2-(ortho-bromophenyl

• skeletons that are inaccessible via Pd-catalyzed cyclization. Keywords: arylation; pyridine; pyrrole; radical cyclization; tris(trimethylsilyl)silane; Introduction Polycyclic heteroaromatic molecules, which have a tunable electronic structure and excellent self-assembling properties, are highly desirable

• metal-catalyzed arylation [17][18][19]. We have recently successfully applied this approach to synthesize the new luminescent heterocyclic system pyrido[2,1-a]pyrrolo[3,2-c]isoquinoline A [17], which turned out to be useful for bioimaging [13] and as a ligand for the preparation of luminescent metal

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• phenyl on the nitrogen atom did not considerably affect the yield (8o–8q, 68–76%). Substrates with benzyl and phenyl groups at the α-position afforded the products 8r and 8s in 74% and 24%, respectively. Substrates with a phenyl group at the β-position underwent arylation with the opposite

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• hand, natural amino acids proline and hydroxyproline are functionalized pyrrolidines that have found great application in organic synthesis as chiral organocatalysts in stereoselective processes [93][94]. Cyclizations involving a position in the starting chiral imine Arylation of chiral sulfinyl imines

• with sodium tetraarylboronates 64 was found to proceed with high diastereoselectivity under rhodium catalysis. Reddy and co-workers applied this methodology to the synthesis of 2-substituted pyrrolidines 66 [95]. The arylation of chlorinated imine (RS)-63 was performed with 2 mol % of an air-stable

• proceeded with high levels of diastereocontrol. The resulting sulfonamide derivatives 95 were transformed into the target spiro compound 97 by performing successive desulfinylation and intramolecular palladium-catalyzed N-arylation. To rationalize the stereochemical course of the addition, DFT calculations

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• the enantioselective β-arylation of cyclic ketones is known [38]. In 2017, Hu et al. presented the possibility of an enantioselective β-arylation of cyclohexanone using the above mentioned ligand L2. Cyclohexanone was in situ oxidized by 2-iodoxybenzoic acid (IBX) to 2-cyclohexenone, that subsequently

• organoboron reagents to enones [3][26][35]. Enantioselective β-arylation of cyclohexanone [38]. Application of L2/Pd(OAc)2 in the total synthesis of terpenes [8]. Plausible catalytic cycle for the addition of phenylboronic acid to 2-cyclohexenone catalysed by L3/Pd(dba)2 [40]. Microwave-assisted addition of

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• apparition of side-products and a drop of the yields (Scheme 40). Recently, a one-pot reaction was reported by Yavari and Nematpour that includes the formation of an hexasubstituted biguanide from TMG, and a copper-catalyzed N-arylation [81]. Using TMG and DIC/DCC as reagents, and 10 mol % of CuI

• -phenanthroline in refluxing DMF as an optimal catalytic system, the formation of the biguanide intermediate proceeded cleanly, followed by N-arylation to provide a series of N1-aryl heptasubstituted biguanides in gratifying 63–81% yield (Scheme 41). Interestingly, Štrukil et al. reported that the use of two

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• berberrubine and berberine derivatives were synthesized by the Cu2+-catalyzed Chan–Evans–Lam coupling of berberrubine with arylboronic acids and subsequent 9-O-methylation. The reaction is likely introduced by the Cu2+-induced demethylation of berberrubine and subsequent arylation of the resulting 10-oxyanion

• substitution [17][18][19][20][21] of berberrubine (1b) have been performed, whereas the direct O-arylation of berberrubine has not been accomplished, yet, most likely because the substrate is not fully compatible with the usual conditions of the corresponding Ullmann or Buchwald–Hartwig coupling reactions

• . Nevertheless, it has been recently reported that 9-O-aryl-substituted berberine derivatives can be isolated by an Ullmann-type arylation of a tetrahydroberberrubine and a subsequent oxidation of the primary product to the respective berberine derivatives 2a–i (Figure 1) [31]. So far, a successful direct

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• polycyclic derivatives was designed. The procedures towards such polycyclic building blocks include C–H-arylation strategies. In the classical Meerwein reaction, aryldiazonium salts are used as the reagents to couple aryl groups to electron-poor alkenes, and this process is assumed to proceed via a free

• work focuses on a metal-free approach for the synthesis of benzofuropyridine analogues. Results and Discussion The synthesis of target compound 13 involved three steps (Scheme 1). C–H Arylation, as needed in the first step, is usually carried out using transition metal catalysis [31]. Furthermore

• , various metal-based approaches for arylation of quinone involving electrochemical [32], oxidative [33], and photochemical methods [34][35][36] are also available in the literature [37]. Langer and co-workers reported the synthesis of benzofuropyridines based on a domino reaction of 3-chlorochromones with

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• functionalization of triazoles under metal-free conditions has been reported. These include the Broensted acid-catalysed N2 alkylation [27], organocatalytic N1 alkylation [28][29], N2-arylation using hypervalent iodine (Scheme 1c) [30], N2-alkylation involving radical intermediate [31], pyridine-N-oxide-mediated N1

• -arylation [32], NIS-mediated N2-arylation [33], etc. Although these are significant advances towards metal-free functionalization of triazoles, many of them suffer from poor regioselectivity. Therefore, a new method for N1-selective alkylation of the triazole moiety under simple, mild and metal-free

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• approaches for the trifluoromethylthio (SCF3) difunctionalization of alkenes, such as cyanation [23], etherification [24][25][26][27], amination [28][29][30], chlorination [31][32], hydrogenation [33], trifluoromethylation [34], phosphonization [35], arylation [36][37][38], trifluoromethylthiolation [39

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• < T < −40 °C in the presence of aromatic nucleophiles, thiophenes 72-Cl and 72-Br could be converted into 74-Cl and 74-Br derivatives via a side-chain arylation reaction. When the reaction was conducted at −40 °C, the reactivity was shown to be governed by the nature of the halogen atom. For the

• brominated derivatives 72-Br, the corresponding side-chain arylation reaction occurred at −60 °C, but a further hydrodehalogenation led to the bromine-free derivatives 75. For the chlorinated derivatives 72-Cl, a similar side-chain arylation−hydrodehalogenation sequence occurred, but an additional Friedel

• –Crafts arylation at the C4-position led to derivatives 76. In this latter case, a two-step one-pot process was developed in order to access derivatives bearing two different aromatic rings. Mechanistic investigations were then undertaken by in situ low-temperature NMR experiments, allowing the

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• catalytic systems Pd(PPh3)4/K3PO4/THF (method A) and Pd(PPh3)4/K3PO4/1,4-dioxane (method B) were less effective. 3-Alkynyl-2-carbazolylazines can also be prepared using an alternative synthetic sequence, i.e., the Suzuki–Miyaura arylation–Sonogashira reaction. It should be noted that in the case of 2,3

• corresponding carbazolyl derivative 4a in 15% yield only (Table 2). The Pd(PPh3)4/K2CO3/1,4-dioxane/H2O catalytic system (method B) was more effective producing 4a in 63% yield. Thus, it was not the way for the synthesis of compounds 2a,b. Arylation of 2,3-dibromopyridine using the Pd(PPh3)4/K2CO3/1,4-dioxane

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• dependence on the nature of the aromatic substituents G was apparent, since arylation took place (in variable yields) with electron-rich aromatic substituents, while it was completely inhibited in the presence of electron-withdrawing groups (path (b’), in Scheme 3). In the case of the triaryl phosphates

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• enantioselectivities (20 examples, up to >99:1 er), with a quantum yield of 0.013. While there has been significant progress using bifunctional catalysts, dual catalytic systems can offer other modes of reactivity. For instance, Jiang et al. developed a urea-catalysed formal arylation of benzofuranones 215, using

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• products, in contrast to the 4-methyl and 4-unsubstituted substrates which do not undergo N1-arylation under similar reaction conditions. Keywords: C–N cross-coupling; Chan–Evans–Lam reaction; pyrimidin-2(1Н)-ones; fluoroalkyl group; boronic acids; Introduction The catalytic formation of C–N bonds in the

• arylation of the nucleophilic nitrogen atom, known as the Ullmann [6][7] reaction, and its modification by Chan and Lam [8] are favored due to the several advantages they offer versus the Pd counterpart (i.e., the Buchwald–Hartwig reaction) such as the lower cost and lower toxicity of the metal as well as

• their tolerance of aerobic conditions [2][9]. The efficiency of the Ullmann arylation has recently been greatly improved through extensive mechanistic investigation, ligand/precatalyst design and optimization studies [10][11][12][13]. As a result, the reaction has become feasible under milder conditions

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• intermediate 29 (Scheme 9) [14]. In 2012, Wu’s team have employed the Pd-catalyzed arylation reaction of sumanene with chlorobenzene and 2-bromo-1,3-dimethylbenzene to afford the aryl-substituted sumanenes 49a (Scheme 10). On the other hand, Higashibayashi et al. has revealed the synthesis of three different

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• economic and abundant source of energy to promote these transformations is in agreement with sustainable and eco-friendly chemistry. Directed C–H activation Pd-catalyzed arylation The first example of dual catalysis merging C–H activation and photoredox catalysis was published in 2011 by Sanford [80]. The

• transformation concerned the direct arylation of various aromatic compounds bearing different DGs with aryldiazonium salts (Figure 20). In her initial study in 2005, Sanford reported a similar arylation and diazonium salts were already identified as appropriate coupling partners. However, harsh reaction

• , pyrimidines, and oximes (Figure 20). The mild arylation proceeded in good to excellent yields over 20 examples and worked with electron-deficient, electron-rich as well as relatively sterically hindered arylating reagents. The mechanism proposed by the authors is presented in Figure 21. First, the DG-assisted

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• - and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels–Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels–Alder cycloaddition with maleimides to furnish octahydropyrrolo

• [3,4-e]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(N-benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-a]isoindol-3-yl)acrylates. A further oxidative

• in governing the endo stereocontrol. Keywords: endo-Diels–Alder stereocontrol; 2-formylpyrrole; intramolecular Heck arylation reaction; non-covalent interactions; pyrroloindoles; pyrroloisoindoles; Introduction Pyrrolizines [1][2] and pyrrolizidines [3][4], abundant in nature [4][5], are among 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

• trapping of the ensuing C(sp3) radical with the deuterated or tritiated thiol results in the incorporation of deuterium or tritium in multiple positions within the product 9.3. C(sp2) radicals Aryl radicals Considering the importance of arylation reactions in organic synthesis [61], aryl radicals are

• important intermediates to develop new synthetic methods [62]. Their reactivity was first explored in the Meerwein arylation as well as the Gomberg–Bachman and the Sandmeyer reaction [63][64][65]. Similar to C(sp3) radicals, aryl radicals add to unsaturated systems, such as (hetero)arenes, alkenes, or

• 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

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• Quentin Lefebvre Christophe Salome Thomas C. Fessard SpiroChem AG, Rosental area, WRO-1047-3, Mattenstrasse 24, 4058 Basel, Switzerland 10.3762/bjoc.16.87 Abstract Herein we report a workflow coupling photoredox-nickel dual-catalyzed N-arylation reactions to benchtop analysis for the efficient

• thus be rapidly accessed, identifying privileged or challenging scaffolds and paving the way for further exploration. Keywords: benchtop analytics; fragment-based library; heterocyclic sp2–sp3 fragments; N-arylation; photoredox-nickel dual catalysis; Introduction Heterocyclic sp2–sp3 fragments are

• often exhibit different reactivity from unstrained substrates [8]. N-Arylation of spirocyclic amines would be a very efficient strategy for the modular synthesis of heterocyclic sp2–sp3 fragments, but their lack of stability to strongly basic conditions and heating might be an issue in palladium

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• Abstract Novel multistage redox tetrathiafulvalenes (TTFs) bearing 6-aryl-1,4-dithiafulvene moieties were synthesized by palladium-catalyzed direct C–H arylation. In the presence of a catalytic amount of Pd(OAc)2, P(t-Bu3)·HBF4, and an excess of Cs2CO3, the C–H arylation of TTF with several aryl bromides

• direct C–H arylation was reported, and the structural and electrochemical properties of the products were clarified [30]. This motivated us to synthesize novel multistage redox-TTFs bearing 1,3-dithiole rings on aromatic rings, 1–3 (Figure 1). In addition, we focused on cross-conjugated systems with 1,3

• -dithiole rings, which are of interest as novel multistage redox systems as well as donor components for organic conductors [1][31][32][33][34][35][36][37][38][39][40][41]. The palladium-catalyzed C–H arylation might offer access to new cross-conjugated molecules bearing vinyl-extended TTF moieties (EBDTs