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

• additives in the petrochemical industry [3]. Besides, 2-benzylanilines also serve as valuable building blocks in synthetic chemistry [4]. The classical route to this kind of aniline derivatives usually starts from parent anilines, which undergo Friedel–Crafts reaction with acyl halides followed by carbonyl

• 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

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• at 298.15 K by Gaussian 16 [81]. Frequency calculations confirmed that optimized structures are minima (no imaginary frequency). The accuracy of computational BDEs of halides using M06-2X/def2-TZVPP is also evaluated and compared to experimental BDEs, demonstrating the reliability of the method (see

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• ], the term “halogen bond” entered the chemical literature in the latter half of twentieth century [8]. Detailed studies of halogen bonding that followed in the late 1990s and early 2000s primarily focused on inorganic molecular and interhalogens, and inorganic and organic halides that are monovalent

• −23.1 kcal/mol (see Supporting Information File 1 for exact values). Likewise, the association of chloride with imidazolium halides 37–40 ranged from −3.7 to −14.3 kcal/mol, which overlaps with the range observed for the diarylhalonium cations. We delved deeper into the periodic trends related to the X

• dots). That is the length of the X–Cl (57–60) covalent bond increases with increasing van der Waals radii of X. Notably, this trend is also replicated for ionic bonds of the halides with sodium; longer ionic bond lengths are observed for larger halides [37]. On the other hand, halogen-bond complexes

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• -mediated reaction with alkyl halides [21]. So far, the literature-reported methods are most often limited to N-unsubstituted pyrazoles or triazoles and pyrazoles being fused to a second (hetero)cycle; the synthesis of promising multi-substituted structures such as 1 has not yet been described

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

• and alkyl radicals, has shown great promise in the synthesis and functionalization of various organic molecules [15][16]. These carbon radicals can be generated in several ways. The first and most straightforward method is the homolytic cleavage of labile C–heteroatom bonds, especially alkyl halides

• [17]. Due to growing concerns about the harmful effects of toxic compounds (e.g., some halides) on the environment, the scientific community is now looking for alternative chemicals that can form these radicals. Moreover, discovering mild strategic approaches for the generation of unstabilized alkyl

• , C–C, and C–heteroatom bond formations. The best known technique for the creation of alkyl radicals is the homolytic cleavage of the C–X bond of alkyl halides by toxic tin hydride [17]. Later, various efforts have been made to replace toxic tin hydrides with other reagents [33][34][35][36][37][38][39

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

• halides, which involved a rhodium-bis(benzyl) complex (Scheme 2) [21]. Following these outcomes, as part of a research program aimed at a wide range of Rh-catalyzed C–C bond-formation reactions, in this paper, we report a Rh-catalyzed Ullmann-type homo-coupling reaction of aryl Grignard reagents. Results

• and Discussion Methodology development In our work towards Rh-catalyzed homo-coupling reactions of benzyl halides, we observed that a similar rhodium–bis(benzyl) complex can also be formed from benzyl halide by using a Grignard reagent instead R2Zn in the presence of RhCl(PPh3)3 to subsequently give

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

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

• ]. Prominent examples include: (i) carbonyl compounds such as benzophenone [31][32] and thioxanthone [33][34][35], (ii) TADF emitters with small singlet-triplet energy splitting [8][36], (iii) substitution with heavy atoms such as sulphur [37] and halides [38] for fast ISC, or a combination of the above

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

• commonly used reaction in synthetic chemistry [50][51]. The selective α-functionalization of carbonyl compounds with organohalides in the presence of bases is one of the most fundamental reactions. This methodology usually suffers from the use of stoichiometric amounts of bases and the use of halides

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

• -cored halides can be broadened by converting C–Hal functions into different functional groups. For example, aldehyde and amine functionalities can be readily derived from C(sp3)–Hal functions through hydrolysis–oxidation [13] or substitution [14], respectively. This is of significant interest in the

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

• what we are discussing in this mini-review. Review Carbonylative synthesis of indoles Synthesis of indoles by Pd(0)-catalyzed carbonylation reaction of halide compounds Processes using organic halides as their starting materials involving the oxidative addition of Pd(0) to C–X bonds to give Ar–PdII–X

• 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

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• employed as acylation reagents [1][2][3]. The strong C–F bond makes acyl fluorides relatively stable towards hydrolysis and easier to handle than other acyl halides [4][5][6][7][8]. Their reactions with nucleophiles are typically less violent than for the corresponding acyl chlorides with acyl fluorides

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• motif in bioactive compounds and the synthetic utility of its olefinic C=C bond. The most extensively explored approach to this transformation is the transition metal-catalyzed C–N coupling between azoles and vinylating agents, including vinyl halides [4], boronates [5], sulfonium salts [6][7][8], and

(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

• could also be oxidised to acid 112, from which redox active ester 118 could be accessed. An alternative approach to 2-oxa-1,4-BCHs involves the C–H-borylation of monosubstituted 2-oxa-BCHs developed by Hartwig and co-workers (Scheme 12C) [57]. Functional groups including halides (in 120b), alcohols (in

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• only 10–25% of the primary chloride for the reaction of tert-butylethylene with HCl in the presence of benzoyl peroxide [33]. c) Several metal halides such as AlCl3, SnCl4, FeCl3, and CuCl exhibit catalytic activities for the hydrochlorination of alkenes. The enthalpy of formation for the hydrogen

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• be difficult to achieve using either radical or polar chemistry alone. In recent years, Gevorgyan, Glorius, Huang and their co-workers reported elegant examples of the carboamination of 1,3-dienes with unactivated alkyl halides and amines under photoinduced palladium catalysis via a radical-polar

• crossover process [47][48][49][50]. However, activated alkyl halides are not suitable for these carboamination reactions due to the direct nucleophilic substitution of activated alkyl halides with nucleophilic reagents under the necessary alkaline conditions [51]. Recently, a Pd-catalyzed alkyl Heck

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• fullerene complexation. Other halides (Br− and F−) also allowed C60 and C70 complexation while tetrabutylammonium cations inhibited the fullerenes' complexation by competing for the cavity of the calix [72]. These calixpyrrole-based tweezers provide a good example of ON/OFF molecular sensors for neutral

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• cyanomethyl (7) groups at the 2′-OH. The synthetic routes to compounds 4–9 are shown in Scheme 1. The 2′-OH of adenosine was alkylated with several alkyl halides in the presence of sodium hydride (NaH). Both the 3′-OH and 5′-OH groups of compounds 10a–e were protected by a TBS group, followed by the selective

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

• 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

• . 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

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

• potentials of the halides that can be reduced in this way, quantum-chemical calculations, and steady-state and transient absorption spectroscopy suggest that UV irradiation accelerates the reactions via cleavage of the dimers to the corresponding radical monomers. Keywords: dehalogenation; n-dopant

• ; reduction; reductive dimerization; Introduction Reductive dehalogenation reactions of organic halides can be used in organic synthesis as a means of generating carbon-centered radical or anion intermediates and could have relevance to the treatment of waste halogenated polymers. While such reactions can be

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• , such as alkyl halides. In this study, the thermal reaction of the La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C afforded single-bonded adducts 2–5 with high regioselectivity. The products were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

• and visible–near infrared spectroscopy. The reaction of La@C2v-C82 with alkyl halides using the same conditions showed no consumption of La@C2v-C82, indicating that the reactivity of La@C2v-C82 toward alkyl halides was effectively increased by one-electron reduction. Single-crystal X-ray diffraction

• produced chemically or electrochemically. C602− is a strong electron donor and potential nucleophile that reacts with electrophiles [6][7][8][9][10][11]. The mechanism for the reaction of C602− with alkyl halides has been studied in detail by Fukuzumi et al., who found that the reaction occurs via electron

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• electrophile compared to other alkyl halides, such as related bromides and chlorides. As a result, an effective iododecarboxylation provides a versatile platform for a range of decarboxylative reactions. Shang and co-workers recently found that aliphatic carboxylates and lithium iodide could undergo