Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• 9,10-dicyanoanthracene radical anion (DCA•−) [29]. This system effectively drives photoredox-mediated reduction and C–C cross-coupling reactions under mild red-light conditions with various aryl halides, an aliphatic iodide, and O- and N-tosylated substrates (Scheme 4a). The authors discuss two

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• conventionally challenging functionalizations, such as N- or O-arylations using aryl halides [29][30][31][32][33][34][35][36][37][38] or arylboronic acids [39][40][41][42], hydrofunctionalizations of unsaturated motifs [25][43][44][45][46][47][48][49][50][51][52][53][54][55][56], the oxidation of alcohols [57

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• test the potential effects on halogenated aromatic structures and no dehalogenation was detected up to 24 hours stirring. The retention of halogen atoms on aryl halides distinguishes this procedure from traditional techniques, such as those involving LiAlH4, which can cause dehalogenation [30][31]. The

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

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

• from di-tert-butyldiazocarboxylate (23), aryl-substituted di-Boc-hydrazines 26 were prepared by the addition of aryllithium species generated in situ by lithium-halogen exchange of aryl halides [55]. Gerstenberger et al. used this entry for the one-pot synthesis of N-arylpyrazoles 25, as depicted in

• . In cases where the α,β-unsaturated carbonyl compounds contain a heteroatom in the β-position, aromatization is triggered by elimination under redox-neutral conditions. Tasch et al. successfully coupled aryl halides with α-bromocinnamaldehyde (51) using a Masuda borylation Suzuki cross-coupling (MBSC

• ) [69] approach without reducing the reactivity of the Michael system. In this one-pot procedure, the borylation of aryl halides with pinacolborane gives aryl pinacolyl boronates 53, which are then coupled with bromoenal 51 to generate the intermediary enal 54. Subsequent cyclization with tosylhydrazine

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• straightforward conditions (Scheme 1). The synthesis of aryl halides is of great academic and industrial importance. Recently, our research group has developed a new procedure for the ortho-selective chlorination of phenols under mild conditions in a short reaction time [26]. The chlorinating species was

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• aryl halides [42]. PEM reactors are also gaining industrial attention. Weber et al. reported a series of large-scale syntheses using PEM reactors [43]. We studied electrochemical transformations [44][45][46][47][48][49] and recently reported the selective reduction of enones using a PEM reactor [50

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• are not always readily accessible. Typically, the preparation methods involve SNAr reactions with N-centered nucleophiles [5], nitroarene reduction [6] and transition metal (e.g., Pd, Cu)-catalyzed C–N cross coupling of aryl halides, aryl sulfonates or arylboronic acid reagents with ammonia or NH

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

• terminal arylalkynes bearing electron-donating and electron-withdrawing substituents were well compatible with this method. The procedure is limited to electron-withdrawing and electron-neutral aryl halides. The presence of a conjugated substituent in the p-position of an aryl halide is crucial for

• nickel-catalyzed cross-coupling reactions with aryl halides to deliver the desired cross-coupled products. Interestingly, in absence of any xanthate, sec-butyl radicals underwent cross-coupling reactions with aryl halides to form sec-butyl arenes, whereas in the presence of xanthate, no undesired sec

• the thiyl radical by [Ir(II)] generates a thiolate anion and [Ir(III)]. Finally, the thiolate anion is converted to the aryl thiol via proton transfer to complete the catalytic cycle. In 2021, MacMillan and co-workers [55] introduced a cross-coupling reaction of alcohols with aryl halides through

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• for integrins which is critical for several diseases. Keywords: biphenyltetracarboxylic acid; homo-coupling; integrin inhibitor; rhodium catalyst; Ullmann-type reaction; Introduction The Ullmann reaction is a coupling reaction of aryl halides using copper, traditionally using metallic copper-bronze

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

• high regioselectivity. Herein, we report the electroreductive hydroarylation of electron-deficient alkenes and styrene derivatives using (hetero)aryl halides under mild reaction conditions. Notably, the present hydroarylation proceeded with high efficiency under transition-metal-catalyst-free

• that a reductive radical-polar crossover pathway is likely to be involved in this transformation. Keywords: aryl halides; C–C bond formation; electroreduction; radicals; visible light; Introduction Alkene hydroarylation is an attractive method for the construction of alkylarenes, which serve as

• versatile building blocks in organic syntheses. To achieve this transformation with high efficiency and predictable regioselectivity, numerous efforts have been made to develop transition-metal-catalyzed reactions based on a C–H activation strategy [1][2][3][4] or the reductive coupling of aryl halides with

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• , hydroaminomethylation, reduction of nitriles and nitro compounds or through reductive amination of carbonyl derivatives [26][27][28][29][30]. However, for example, cross-coupling reactions with alkyl or aryl halides generate considerable amounts of waste (Scheme 2A). Even though many different approaches exist for

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

• be employed in two variants modulated by light irradiation. This external switch can be used to selectively trigger side-chain or core halogenation. Keywords: aryl halides; benzyl halides; bromination; sustainability; Introduction Activation through halogens has become a key strategy in achieving

• bonds of aryl halides also exhibit high reactivity, particularly towards transition-metal-mediated cross-coupling processes or Ar-SN reactions. Benzyl and aryl halides, collectively referred to as 'aryl-cored halides', have found extensive applications across various fields, including synthesis [1

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• functionality as well as Buchwald–Hartwig amination involving aryl halides. Thermal studies Thermal stabilities of DCPQs 1a–6a and DPQDs 1b–7b were evaluated using thermogravimetric analysis (TGA; Figure 2 and Table S4 in Supporting Information File 1). The thermal stability of the DCPQs is attributed to their

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

• functionalization of indoles to 3-substituted indoles Functionalization through direct C–H alkoxycarbonylation The transition-metal-catalyzed carbonylation of aryl halides, triflates, and tosylates with carbon monoxide and an alcohol was first pioneered by Heck and co-workers in 1974 [64][65]. Since then, this

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

• bases in the presence of Pd(OAc)2 as the catalyst (5 mol %) in DMA at 150 °C. This catalyst precursor is known to efficiently promote the direct coupling of 5-membered ring heteroarenes with aryl halides [25]. Cs2CO3 and K2CO3 proved to be totally inefficient bases, while acetate bases gave the desired

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

• . Finally, single electron oxidation of 169 at the anode, followed by rearomatization via proton-transfer forms the alkylated heterocycle 170. As discussed in Scheme 25, the Ni-catalyzed cross-electrophile coupling between redox-active esters and aryl halides requires the addition of a stoichiometric

• cathode surface restores the Ni0 species 175 giving rise to a new catalytic cycle. Reductive cross-electrophile couplings that incorporate redox-active esters and aryl halides have the potential to simplify the syntheses of drug-like compounds through C(sp3)–C(sp2) bond formation. However, their synthetic

• -rich (hetero)aryl halides was equally effective (Scheme 36). In addition, the preparation of unnatural amino acids in multigram scale [115], along with the syntheses of complex terpenes [116] and (+)-calcipotriol [117] have showcased the vast synthetic potential and broad applicability of NHPI esters

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• trifluoromethyl groups [20] and the cross-coupling of aryl halides [21]. Like phosphonium salts in general are used as catalysts [22][23], phosphonium salts based on ortho-hydroxy-substituted phosphines received particular attention because of their zwitterionic nature and have been used as catalysts in the

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• dimers reduce halides that have reduction potentials less cathodic than ca. −2 V vs ferrocenium/ferrocene, especially under UV photoexcitation (using a 365 nm LED). In the case of benzyl halides, the products are bibenzyl derivatives, whereas aryl halides are reduced to the corresponding arenes. The

• to initiate the coupling of aryl halides and arenes [5]. However, even relatively easily reduced organic halides have sufficiently cathodic reduction potentials (e.g., ca. −1.6 V and −1.8 vs ferrocenium/ferrocene (FeCp2+/0) for diethyl bromomalonate [6] and 4-iodotoluene, see Table 2, respectively

• aryl halides (RX) and discuss the scope and possible mechanism of these reactions. Results and Discussion Reaction of (Y-DMBI)2 with benzyl bromide We began our investigations of dehalogenation reactions using benzyl bromide (BnBr, 1a), which has a reduction peak potential (Epc) of −1.6 V vs FeCp2+/0

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

• , commercially available aryl halides are chlorides [37][38], with potentials for reduction that almost exclusively lie beyond the threshold of monophotonically-excited photoredox catalysts (i.e., more deeply negative than E1/2 = −2.0 V vs SCE). Considering this, state-of-the-art developments have focused on the

• 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

• aryl halides and trialkylphosphites (14) via a similar conPET mechanism (Figure 7) [47]. Notably, even 4-bromoanisole could be reductively activated and phosphorylated in 58% yield (15b). Reports from Eggins [48], Lund and Eriksen [49] have shown that upon excitation, the radical anions of

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

• 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

• groups used Pd(OAc)2 as catalyst with 1,10-phenanthroline as ligand. The group of Yu used aryl halides 137 as coupling partner, whereas the group of Tan utilized aryl tosylates 142 as coupling partner (Scheme 26). The Yu group also applied the developed protocol for the synthesis of the drug molecule

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

• thioethers from aryl halides and triflates through palladium catalysis [50][51]. Scheme 10 provides a retrosynthesis of amination in the synthesis of dibenzo[b,f]azepine 45 as an example. Arnold et al. [30] reported an excellent method for the convergent synthesis of variable sized dibenzo-fused heterocycles

• . Among these, Heck reaction conditions allowed for the coupling of aryl acrylates 50 to aryl halides 48 and 49, followed by intramolecular Pd-catalysed amination or etherification to give C-10 carboxylates of dibenzo[b,f]azepine 55 and dibenz[b,f]oxepine 54 in good yield (Scheme 11). However, no ring

• 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

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