Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• the additional electron transfer to form the corresponding anions is a highly favorable pathway due to the more positive reduction potential of radicals than that of the starting halides [38], employing redox mediators enables the generated aryl radicals to participate in radical arylation reactions

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• catalyst in the sulfonylation/arylation of styrenes and as a triplet sensitizer in energy transfer catalysis. The singlet lifetime is sufficiently long to exploit the exceptional excited state reduction potential for the activation of 4-cyanopyridine. Photoinduced electron transfer generating the radical

• rule [43]. However, helicenes have not been broadly considered as potential photocatalysts or sensitizers or their applications were unsuccessful [44]. Recently, one of our groups exploited the highly reducing polyaza[7]helicene (Aza-H, see Scheme 1 for its structure) for sulfonylation/arylation three

• mechanism of the recently reported sulfonylation/arylation [45][46] reaction using laser flash photolysis (LFP). LFP is a powerful spectroscopic tool in photocatalysis that allows us not only to distinguish between energy and electron transfer but also to detect transient triplet states and radicals

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• modifying their physical properties, and stability and controlling the reactivity of arylation processes, as demonstrated in various studies [9][10]. For instance, the Gaunt group reported that the use of a fluoride counterion in diaryliodonium(III) salt can trigger phenol O-arylation by activating the

• -arylation using aryl(2,4,6-trimethoxyphenyl)iodonium(III) acetates [13]. In this process, the acetate ligand acted as a base to activate the phenol group and positioned it in proximity to accomplish the smooth SNAr reaction. The synthesis of diaryliodonium(III) salts with various counterions, such as

• triflate (TfO−) [14], tetrafluoroborate (BF4−) [15], tosylate (TsO−) [16], and others [17], has been extensively studied, as they play a key factor in the participation of iodonium salts in diverse arylation reactions. Recently, efficient syntheses of diaryliodonium(III) trifluoroacetates have been

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• regioselective Ru-catalyzed direct carbonylative arylation of heterocycles developed by Beller et al. in 2014 [77]. In this paper various heterocycles were investigated including five examples of indoles. Another example was reported by Driver an co-workers, who developed the Pd-catalyzed direct aryl C–H

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation

• -pyrroles posed some challenges due to substrate instability and undesirable side reactions. In 2003, we reported the Heck–Matsuda arylation of N-protected 2,5-dihydro-1H-pyrroles [10] to obtain 4-aryl-γ-lactams in a racemic manner [11], thus demonstrating the feasibility of this transformation. The γ

• presence of a methoxy group after the Heck–Matsuda reaction indicates methanolysis after arylation. Given the importance of the lactam rings, we envisioned a sequential Jones oxidation protocol without isolation of the methyl N,O-acetal products to obtain the corresponding lactams 4. As observed in

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• 91 and 92 enabled the metallaphotoredox arylation (to 93) and alkylation (to 94) of the cubane core. Comparative physicochemical or biological data for the 1,2-cubanes was not reported. Isosteres of meta-substituted benzenes Many of the scaffolds previously discussed as potential bioisosteres for

• 1,4-BCHs (Scheme 11B) [55]. From carboxylic acid 100e, Curtius rearrangement led to amine 101 and a photoredox decarboxylative conjugate addition to diester 102. From boronate ester 100f, oxidative deborylation led to alcohol 103, arylation led to furan 104 and Matteson homologation to boronate ester

• methylation of the intermediate diacid. As for the 1,2-cubanes, the authors were able to derivatise this general building block into a range of other 1,3-cubanes via metallophotoredox catalysis using acid 167 and redox active esters 168 and 169 (Scheme 17B) [51]. Arylation (to 170), amination (to 171) and

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• investigations demonstrated the ability of diaryliodonium salts for selective mono-arylation of 2-naphthols [34]. In this context, we embark on a strategy to modify the neighbouring position of the diaryliodonium salt with an ester group, presenting a novel copper-catalysed regioselective arylocyclization of

• for the synthesis of functional materials via cross-coupling reactions. Next, we extended our investigation to 1-naphthol in this reaction, and found that the arylation of 1-naphthol was achieved selectively at the C-2 position. The cascade cyclization resulted in the corresponding products 3an and

• 3au and 3av were produced in 34% and 39% yields, respectively, in which methoxy and tert-butyl groups were located in the para position to the hydroxy group (Table 2, entries 20 and 21). In the case of 3al, the mono-arylation of naphthol generated 3al’ in 20% isolated yield, which is the reason for

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• diphenyl analogue 17f was isolated as a side product upon arylation with B(C6F5)3, debromination was only observed in traces. Both aminoboranes 17d and 17e were then cleaved separately in clean conversions using formic acid to afford the desired substituted 6-bromo-5-(2-tolyl)-2,3-dihydrothiazolo[4,5-b

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• palladium-catalyzed direct intermolecular arylation, followed by a direct intramolecular arylation step. As the C–H bond activation of several benzene derivatives remains very challenging, the preparation of fluoranthenes from 1,8-dibromonaphthalene via Suzuki coupling followed by intramolecular C–H

• activation has also been investigated to provide a complementary method. Using the most appropriate synthetic route and substrates, it is possible to introduce the desired functional groups at positions 7–10 on fluoranthenes. Keywords: catalysis; C–H bond functionalization; direct arylation; fluoranthenes

• tuned, or enables them to be linked to other useful units [1]. There are several synthetic routes to fluoranthene derivatives, but in most cases several steps are required [2][3][4][5]. Over the past two decades, the Pd-catalyzed C–H arylation of a wide variety of arenes has led to a revolution in the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• with one another. With the new avenues offered by the advent of nanocatalysis, it did not take long for its application in the Friedel–Crafts arylation of indoles with aldehydes, since the development of more resource-efficient catalytic pathways for the synthesis of BIMs had received great interest

• not seen wide applications in nanocatalysis despite its numerous benefits. Therefore, Ozturk made it usable by coupling it with an ionic liquid, creating g-C3N4-SO3H nanoparticles, which displayed high catalytic activity for the Friedel–Crafts arylation of indoles with aldehydes. The optimum product

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• -catalyzed decarboxylative functionalizations employing RAEs have been established (Scheme 24). Baran and co-workers have reported arylation protocols (Scheme 24A) using arylzinc reagents [84][85], Grignard reagents [85] and arylboronic acids [86], as well as decarboxylative alkenylation [87] (Scheme 24B

• of RAEs with organozinc reagents under Co-catalysis, effecting diverse arylation, alkenylation, and alkynylation reactions [92]. The second type of reaction is referred to as cross-electrophile coupling and involves the Ni-catalyzed reaction of NHPI esters with aryl- and vinyl halides under reducing

• halides [93][94], bromoalkynes [95], bromoalkanes [96], and pyridyl thioesters [97] (Scheme 26A). Likewise, the Rousseaux group has recently documented the arylation of NHPI esters obtained from cyclopropanecarboxylic acids [98] and malonic acid half amides [99], while the Reisman lab has pioneered an

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• derivative 21 was synthesized in six steps in 14% overall yield from 3-bromothiophene (17, Scheme 7). In the first step, the sulfur atom embedded in the final thiepine ring was introduced via a palladium-catalyzed S-arylation of 3-bromothiophene in the presence of potassium thioacetate, to afford the

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• strategy was reported by Laha et al., aiming to access dibenzodiazepinone structures via a double N-arylation of 2-aminobenzamides with 1,2-dihaloarenes using a palladium-based catalytic system [15]. Mechanistic investigations supported the fact that the regioselective N-arylation of the 2-aminobenzamide

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• reaction is possible upon elimination of the resulting benzylic alcohol on D, allowing another arylation forming E [18]. This complex sequence of transformations is herein applied to the synthesis of 1-aryltetralines, analogues of cyclolignan natural products having important medicinal applications [19][20

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• -triazolines and their derivatives via tandem 1,2-addition/cyclization reactions between trifluoromethyl acylhydrazones and cyanamide [105] (Scheme 17b). Afterwards, Hu et al. developed a method for the N-arylation and N-alkylation of trifluoromethyl acylhydrazones with diaryliodonium salts and alkyl halides

• acylhydrazines. Synthesis of trifluoromethylated cyanohydrazines and 3-trifluoromethyl-1,2,4-triazolines. N-Arylation and N-alkylation of trifluoromethyl acylhydrazones. [3 + 2]-Cycladditions of trifluoromethyl acylhydrazones.

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• , arylation, hydroxypropylation, amination, etherification, etc.) giving rise to synthetic CD derivatives with greater water solubility [2]. Thanks to their unique structure, CDs can offer exclusive advantages by allowing the entrapment of lipophilic molecules inside their inner cavities. This inclusion

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• succeeded in synthesizing various diaryl(alkyl) sulfides 5 through the sulfenylation of unactivated arenes 4 with an electrophilic sulfur reagent in the presence of a palladium catalyst (Scheme 3) [45]. In the second phase, dibenzothiophene derivatives 6 were obtained via subsequent intramolecular arylation

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• carboxylation, C(sp2)–H alkenylation and allylation, C(sp2)–H arylation, C(sp2)–H amidation, and C(sp2)–H thiolation. Preceding the section of applications, a brief description of the structure of NHCs, nature of NHC–metal bond, and methods of preparation of NHC–Cu complexes is provided. Keywords: conjugate

• arylaluminium reagents to five-, six-, and seven-membered β-substituted cyclic enones (Scheme 42). It is obvious that the NHC–Cu(I) complexes are generated in situ through transmetallation. For arylation reactions, Me2(Ar)Al reagents were used. The substrates having a variety of substituents (R = CH2Bn, n-Bu

• )–H Arylation In 2014, Cazin and co-workers accomplished the C(sp2)–H arylation of acidic arenes by using a cooperative NHC–Cu/NHC–Pd catalytic system in the presence CsOH (Scheme 73) [95]. [(It-Bu)CuCl] changes in situ into the catalytically active species [(It-Bu)CuOH], which induces C(sp2)–H

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• the same year, Correa et al. reported the FeF2-catalyzed direct α-arylation of azoles with ethers (Scheme 25) [86]. This approach was suitable for assembling a wide variety of functionalized heterocycles, representing an attractive strategy for the C–H alkylation of azoles. The authors also discussed

• tetrahydropyrans. CDC of thiazole with cyclic ethers. Cu(I)-catalyzed oxidative alkenylation of simple ethers. Cross-dehydrogenation coupling of isochroman C(sp3)–H bonds with anisole C(sp2)–H bonds. Pd(OAc)2/Cu(OTf)2-catalyzed arylation of α-C(sp3)–H bonds of ethers. Cu-catalyzed C(sp3)–H/C(sp2)–H activation

• -catalyzed formation of 1,1-bis-indolylmethane derivatives. Alkylation of coumarins and flavonoids. Direct CDC α-arylation of azoles with ethers. CDC of terminal alkynes with C(sp3)–H bonds adjacent to oxygen, sulfur or nitrogen atoms. Alkylation of terminal alkynes. Co-catalyzed functionalization of glycine

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• these ylides (e.g., 75), they surmised that the nitro group was best suited to blocking the proximal σ-hole, thereby preventing non-productive reaction pathways (e.g., thioamide arylation) from occurring. Takemoto and Kobayashi have theorized that an equilibrium should exist between Lewis-basic

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• halides and the coupling products were obtained in good yields (52–74%) (Figure 4B). To suppress the rapid HAT with solvent DMF that yields the dehalogenated product, DMSO was chosen as solvent for the C–H arylation. When applying the catalytic protocol to 2-allyloxy-1,3,5-tribromobenzene, the 5-exo-trig

• enabling controlled bond activations [45]. Regarding the reductive C–C arylation, the application of the xanthene dye rhodamine 6G (Rh-6G) as a catalyst for the reduction of heteroarenes bearing two or three bromine atoms (e.g., 6) under irradiation with green light (λ = 530 nm) gave monosubstituted

• potentials whereas a second excitation with blue light yields the excited state *Rh-6G• that can reduce substrates with much more negative reduction potentials (Epred < −2.4 V vs SCE). The authors also demonstrated the applicability of Rh-6G for reductive arylation reactions (Figure 5D). While the use of PDI

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• .19.76 Abstract Copper sulfate catalyzed an efficient, inexpensive, and environment-friendly protocol that has been developed for N-arylation of amines with 1,3-cyclohexadione-derived aryliodonium ylides in water as a green solvent. Aromatic primary amines substituted with electron-donating as well as

• electron-withdrawing groups on the aryl ring reacted smoothly with iodonium ylides to give the corresponding diarylamines with good to excellent yields. Also, secondary amines underwent N-arylation to deliver tertiary amines with moderate yields. Keywords: amines; arylation; C–N bond formation; iodonium

• anti-inflammatory agent (Figure 1). Owing the importance of arylamines and their biological significance, the surge of development of innovative methods for their synthesis has been always an area of interest [12]. Specifically, the metal-mediated arylation reactions have witnessed significant

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• , diversely functionalized pyridines have been synthesized via C–H activation under transition-metal and rare earth metal catalysis, including C–H alkylation, alkenylation, arylation, heteroarylation, borylation, etc. Recently, metal-free approaches have also been developed for the C–H functionalization of N

• alkenylated product 109 (Scheme 21b). Arylation C-2 Arylation Owing to the remarkable role of aromatic C–H arylation reactions in organic synthesis abundant methods have been reported for aromatic C–H arylations using different arylating coupling partners, such as for instance, aryl halides. In 2014, using

• organoboron coupling partners, Wu and co-workers [91] reported a protocol for the Cu-catalyzed C–H arylation of pyridine N-oxides 9 with arylboronic esters 114 and prepared C2-arylated pyridines 115 in moderate to good yields (Scheme 22). By using an inexpensive Cu catalyst, the method allows for the simple

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• precursor 102 and the complementary aldehyde 103. 3.4 Catellani-type reaction The Catellani reaction involves palladium-norbornene cooperative catalysis to functionalise the ortho- and ipso-positions of aryl halides by alkylation, arylation, amination, acylation, thiolation, etc. [63]. Della Ca' et al. [64

• derivatives follow standard reactions of secondary arylamines and as such will be only briefly discussed with selected examples. Huang and Buchwald [73] reported a palladium-catalysed arylation of 1a. Treatment of 1a with aryl halide 140 or 141 gave excellent yields of N-aryldibenzo[b,f]azepines 142 (Scheme

• yield proved to be good to excellent and sterically hindered aryl rings were tolerated. This method was applied by Huang et al. [74] to prepare a series of fluorescent compounds in excellent yield. Copper- and nickel-catalysed arylation were reported as alternatives to the Pd-catalysed arylation of 1a

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• -methylphenyl)benzothiophene-fused 2-hydroxy-1-oxa-2-phosphacycloundecane 2-oxide 36 in 83% yield (Scheme 7) [22]. 1.1.2 Synthesis via other C–C bond formations: The palladium-catalyzed intramolecular Heck arylation of 2-bromophenylmethyl alk-1-enylphosphinates 37 provides access to 4-alkylidene-1,4

• palladium-catalyzed intramolecular arylation of 3-(2-bromophenyl)propyl alkylphosphinates 61 approached the synthesis of 3,4,5-trihydrobenzo[c][1,2]oxaphosphepine 1-oxides 62 in moderate 39–45% yields in the presence of triethylamine in dry toluene at 100 °C [33]. When the substrates were extended to 5

• -bromohex-5-en-1-yl methylphosphinate (63), 2-methyl-3-methylene-1,2-oxaphosphepane 2-oxide (64) was obtained in low 17% yield at 110 °C (Scheme 13) [34]. The Mn-catalyzed intramolecular radical arylation of 2-(naphthalen-1-yl)ethyl phenylphosphinate (65) gave a mixture of 4-phenyl-1,2-dihydronaphtho[2,1-c