Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• (TFE) as a solvent, yielding 2,2,2-trifluoroethyl pyrazole-5-carboxylates 72 (Scheme 25) [103]. A limitation of the method is that methanol formed in the first reaction step also reacts with the acid chloride to produce unwanted byproducts. The carbonylative Heck coupling of aryl bromides with butyl

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• using tertiary alkyl oxalates and aryl bromides (Scheme 10). This is achieved through the synergistic combination of photoredox and nickel catalysis. This approach facilitates the formation of diverse trisubstituted olefins with outstanding regioselectivity and syn-stereoselectivity. The proposed

• photocatalysis. The generated alkyl radicals then undergo the desired addition with alkyne to produce alkenyl radicals that via Ni-catalysed coupling reactions with aryl bromides form trisubstituted alkenes Z-selectively. Internal alkynes are not suitable for this transformation due to the steric reason, but

• achieving good syn-stereoselectivity. In 2019, using a similar concept, they reported 1,2-alkylarylation of alkenes with alkyl oxalates and aryl bromides under visible-light photoredox and Ni catalysis (Scheme 11) [48]. This protocol was applicable to a wide range of substrates, such as nonactivated alkenes

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

• , 3ca). Products bearing p-methylsulfonyl (3da) and m-methoxycarbonyl (3ea) groups were obtained from the corresponding aryl bromides instead of chlorides under otherwise identical reaction conditions. The steric hindrance of the ortho-substituent did not have a large influence on the reaction

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• halogenation. Of the two alternatives, the latter is more advantageous, due to three favourable features [65][66]: (i) Optimal control as each ring halogenation inhibits further ring halogenations, (ii) ring halogenation do not negatively affect benzylic bromination, and (iii) aryl bromides often display

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

• %) using again a large excess of DBU base (7 equiv) also allowed to prepare unsubstituted fluoranthene in 87% yield (Scheme 1c) [22]. The reaction of naphthol with aryl bromides followed by nonaflation and intramolecular C–H activation for the access to fluoranthenes has also been reported [23]. Most of

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• , and aryl bromides as bromination reagents are limited. Wan and Li, respectively, demonstrated a few examples of a one-pot N-acylation and C5–H bromination of 8‑aminoquinolines using acyl bromines acting as both acyl and halide donors [25][26]. The groups of Lei and Fang independently realized the

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• researchers efficiently conducted palladium-catalyzed C–H activated annulation reactions, involving oxanorbornadiene derivative 26 and aryl bromides including dibromoanthracene 27 [38]. Subsequent aromatization reactions were then carried out, resulting in the successful synthesis of the target POAs with high

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• nickel-catalyzed coupling of aryl bromides with an α-hydroxytrifluoroethyl radical for the synthesis of trifluoromethyl aryl alcohols [39]. Encouraged by this work, we envisioned that the nickel-catalyzed coupling of carboxylic acids-derived acyl electrophiles with an α-hydroxytrifluoroethyl radical

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

• reductants as a theme of ongoing debate [39]. Nonetheless, this protocol enabled the reduction of various electron-poor aryl iodides and aryl bromides and, for the first time, the reduction of aryl chlorides (albeit electron-poor ones) via visible light PRC in good to excellent yields (35–98%) (Figure 4A

• describes a chloride salt, the photocatalyst itself is a monocationic species (Rh-6G+) that forms a neutral radical (Rh-6G•) upon reductive quenching. The radical Rh-6G• itself (E1/2 = −1.0 V vs SCE) can directly reduce certain aryl bromides or other substrates with sufficiently accessible reduction

• was mostly limited to electron-poor aryl halides, *Rh-6G• could reach a step further and reductively activate electron-rich aryl bromides such as 4-bromotoluene and 4-bromoanisole, albeit providing low (27% and 25%) yields of the coupled products 4d and 4e, respectively. Building on this work, König

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

• induces a retro-Diels–Alder reaction, giving dibenzo[b,f]azepine 110 in good yield (Scheme 23). The authors synthesised a series of derivatives, with substituents including -OMe, -Me, -Cl and –F, with good yield (50–78%) in one step. In the follow-up reported in 2018 [65], the method was extended to aryl

• bromides and electron-withdrawing groups. The authors found that the addition of potassium iodide, and thus in situ palladium-catalysed halogen exchange, improved the yield of dibenzo[b,f]azepine 110. Unsymmetrical derivatives of 110 containing -CO2Me, -CF3, -NO2 and -CN substituents were synthesised in

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• intramolecular amination of aryl bromides [27]. Recently, Nguyen and Retailleau introduced a TFA-catalyzed umpolung strategy with 2-aminothiophenols, preparing several 2H-benzo-1,4-thiazine derivatives 5 in high yield [28]. 3-Phenyl-2H-benzo-1,4-thiazine, an earlier representative of this family, was found to

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• halides in a test tube [15]. They found that a Pd(dba)2/DPEphos catalytic system was effective for aryl bromides, and aryl chlorides reacted more efficiently when XPhos was used as the ligand [15]. Although their achievements are remarkable, this protocol is only applicable to liquid substrates, which can

• no homocoupling product of 1a was formed, or only trace amounts (<1%) were formed in all cases. Under the optimized reaction conditions (Table 1, entry 1), we explored the substrate scope of aryl bromides for the solid-state borylation (Scheme 2). The reactions of aryl bromides bearing electron

• ), tetraphenylethylene (1l), and anthracene (1m) reacted with diboron 2 to form the desired products (3f–m) in high yields. Next, the substrate scope of liquid aryl bromides was investigated (Scheme 3). We found that the present mechanochemical conditions were applicable to the solid substrate and various liquid

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• -halosuccinimide (NXS, X = Br, I) as halogen source [47]. Two years later in 2017, Eslami's group applied a ball-milling method to synthesize aryl bromides and α-bromoketones with N-bromosuccinimide (NBS) and MCM-41-SO3H catalyst and no liquid additives [48]. In 2018, Wang and co-workers developed the ball-milling

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• recovered by applying an external magnet and reused for successive five runs. Functional groups including nitro, carbonyl, and methoxy on the aryl halide were compatible with the catalyst. Aryl iodides gave better yields when compared to aryl bromides. A good synergistic effect of the nanoparticles with the

• bonds. This protocol involves the visible light-assisted Sonogashira coupling of aryl bromides and terminal alkynes in the presence of the Co(C9H9NO2)3 complex as the catalyst (Scheme 34) [45]. This novel catalytic system provided 23 alkyne products in a substrate scope study using ethylene glycol as

• the addition of 2-(hydroxyimino)-1-phenylpropan-1-one. This reaction displayed promising yields by the use of ethylene glycol as additive. Aryl bromides with electron-donating and electron-withdrawing substituents in the para position gave the desired coupled products in moderate to excellent yields

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• strategy for aldehyde C–H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the

• through this step were used in a well-stablished nickel-catalyzed cross-coupling reaction [19][27][28][29][30] with aryl bromides as a proof of concept, leading to the synthesis of aryl ketones. We also present computational calculations of the HAT reaction step with the DABCO radical cation as the

• optimized reaction conditions. Also, when other aldehydes or aryl bromides were tested in the absence of DABCO, a very strong dependence on the aryl bromide electronics emerged, leading to diminished yields, remarkably for electron-rich aryl bromides (Table 1, entry 10 and Supporting Information File 1

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• products 7 (Scheme 3). It is worth noting that 3-acetoxyquinuclidine serves as both the HAT catalyst and the base in this reaction system. Furthermore, several cyclic and acyclic amine 6 substrates were used as C‒H nucleophile coupling partners for (hetero)aryl bromides 3. Two additional examples for the

• (III) species 4-IX, which undergoes reductive elimination to release the desired product 10a. Concurrently, Molander and co-workers also reported a related nickel-catalyzed arylation of α-heteroatom-substituted or benzylic C(sp3)‒H bonds by aryl bromides 3 at room temperature using an iridium

• photocatalyst, substoichiometric 4,4′-dimethoxybenzophenone (DMBP) additives, and visible light (Scheme 6) [57]. A variety of cyclic and acyclic ethers 9 reacted with (hetero)aryl bromides 3 under the mild reaction conditions to give the desired products 10 in moderate to good yields, however, with longer

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• -1,3,2-dioxaborolane, THF, −78 °C, 0.45–2 h, rt, 18 h (57%); R = Bn: bis(pinacolato)diboron, Pd(dppf)Cl2·CH2Cl2 (cat.), KOAc, dioxane, 80 °C, 17 h (55%). Synthesis of aryl bromides 9. Conditions: f) BBr3, −78 °C to rt, 18 h (71%); g) R = TBS: TBSCl, DMAP, imidazole, DMF, 55 °C, 4 h (73%); R = Bn: BnBr

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

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

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• obtained under photoredox-catalyzed conditions by using diaryldiodonium salts [57], arylsulfonyl chlorides [63], or aryl bromides [64] as the source of aryl radicals. A peculiar case is described in Scheme 7, path b, where arylhydrazines functioned as arylating agents to afford derivatives 7.4a–d by having

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

• the nature of the halide: as a trend, aryl iodides are easier to reduce than aryl bromides and aryl chlorides [67][77]. Under organophotocatalytic conditions, the reduction can be achieved following two main strategies for accessing stronger reduction potentials: (a) tuning the electronics of the

• heteroarylated to give the desired dehalogenated products 13.3 or arylheteroarenes 13.4. Other organic dyes, such as dicyanoanthracene (OD5) and rhodamine 6G (OD14), have been successfully used in similar conPET strategies for the aryl radical-mediated derivatization of aryl bromides [82][83]. A similar double

• corresponding pyridinium and the desired carbamoyl radical. The latter can be intercepted by an organonickel species resulting from the oxidative addition of the nickel catalyst to the aryl bromides 19.2. The arylamides 19.3 are obtained following a reductive elimination, and the resulting Ni(I) species is

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

•  14, a). One year later, they demonstrated that these copper-based reagents ((Phen)CuCF2RF, RF = F, CF3 and CF2CF3) were efficient in a two-step sequence reaction (borylation/perfluoroalkylation) allowing the functionalization of either sterically hindered arenes or aryl bromides with the CF2CF3 and

• dealt with the copper-mediated perfluororalkyaltion of (hetero)aryl bromides using the previously developed PhenCuRF [69]. Although the trifluoromethylation reaction was mainly studied, the methodology was efficiently extended to the pentafluoroethylation of various heteroarenes such as pyridine

• (hetero)aryl bromides (11 examples, up to 98% 19F NMR yield) via the in situ generation of the suitable CuCF2CF3 from CuCl, KOt-Bu or NaOt-Bu and ethyl pentafluoropropionate [73]. Note that the methodology was also applied to the functionalization of a vinylboronic acid and a vinyl bromide (Scheme 18

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

• , 29 combinations of bicycloalkylamines or spirocyclic amines with (hetero)aryl bromides were probed using this workflow, and the results are depicted in Scheme 2 and Scheme 3. To provide attractive heterocyclic sp2–sp3 fragments, we mainly focused on coupling 3-bromopyridine to five different classes

• reactions, and ranged from 6% to 50% for copper-catalyzed cross-coupling reactions [13]. Much information could be obtained from this screening. Electron-deficient aryl bromides led to better yields than neutral and electron-rich partners, as observed in previous reports on photochemically- or

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

• step from pristine TTF and 5, respectively, through palladium-catalyzed C–H arylation (Table 1). When the aryl bromides 6a,b were allowed to react with TTF under the conditions A, the products 1a,b were produced in 46 and 48% yields, respectively (Table 1, entries 1 and 2). Attempted isolations of