Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• afford propargyl halide C. Finally, intermediate C reacts with the secondary amine to give the propargylamine product D. As outlined in the catalytic cycle, the presence of a base plays a dual role: co-activation of the alkynyl C–H bond through deprotonation and trapping of the HCl produced during the

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• cross-coupling reactions were performed by an organic halide reacting with an organotin compound. A great advantage of the used organostannanes is the easy accessibility, and their high air and moisture stability, so that usually a wide range of functional groups can be introduced under mild conditions

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• groups Directing from glycosylation with glycosyl halide donors by Fischer [72] and Michael [73] and later modified by Koenigs and Knorr [74], there have been reports of the synthesis of a wide range of glycosides involving the Walden-type inversion in the anomeric position. This concept of Walden

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• those that lead to α-alkyl-substituted compounds, is still challenging [27]. For example, in the SN2 reaction of alkyl halides with sulfoxonium ylides, the initially formed α-alkyl-substituted ylide reacts further with the halide to expel the sulfoxide and ultimately generate an α-halogenated product

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• firstly through the coordination of an alkene by the HVI reagent, which activates it toward intramolecular attack by an internal nucleophile. Following this, substitution of the iodane(III) can occur from the nucleophilic halide in solution to reveal the halo-cyclised product (Figure 2). In this review

• , we have collected and described the HVI-mediated halocyclisation reactions reported in the literature for each halide. We have organised the examples firstly by the halide nucleophile, and then secondly by the internal heteroatom nucleophile involved in the cyclisation. The selectivity (chemo-, regio

• is an important approach that yields a broad variety of heterocycles under mild and efficient oxidative conditions. The internal nucleophile, length of the carbon chain and halide can be designed such that a very broad range of 5-, 6- and 7-membered heterocycles can be accessed. The identity of the

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• group from position 4, and then regioselective vicinal functionalization of the generated aryne. The method's compatibility with halide-substituted aryl compounds enhances its versatility and practicality. Moreover, the completion of reaction within a mere 40 minutes at room temperature underscores its

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• 64% yield (Table 1, entry 8). Finally, CsCl was substituted by silica, which, to our surprise, blocked the product formation completely (Table 1, entry 9). Apparently, the presence of an alkali halide salt was beneficial, most likely by stabilizing the consistency of the reaction mixture leading to a

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

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• orbitals. Keywords: organofluorine; pyran inter-halide; solid-state conformation; solution-state conformation; Introduction Polyfluorinated pyran analogues of carbohydrates have attracted attention over the years. This class of glycomimetics has great biological potential with useful applications [1][2

• ][3][4][5][6][7]. What about other halogens? Pyran inter-halide analogues of carbohydrates were rarely investigated as new tools in glycobiology [8]. This is surprising since the incorporation of halogens can improve cellular uptakes and enhance membrane binding and permeation [9][10][11]. In addition

• , halogen bonding is an important interaction in biological systems [12][13][14][15][16][17] and the beneficial effect of the chloro substituent has been reviewed recently [18]. As a result, there is a lack of efficient synthetic strategies to access multivicinal inter-halide stereocenters (i.e., contiguous

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• donors [16][17] from our group as well as of dicationic N-heterocyclic-substituted monodentate catalysts by Nachtsheim [15]. While such compounds are necessary to activate neutral substrates in more challenging reactions, monodentate and monocationic congeners provide sufficient activation in halide

• halide abstraction is the crucial step towards the formation of a catalytically active gold species [18][19]. Furthermore, iodonium species 1BArF–4BArF have been shown to be halide abstracting agents in the Ritter-type solvolysis of α-methylbenzyl bromide and via the crystal structures of 1Cl, 2Cl, and

• 3Cl which resulted from crystallization of the respective cation with the abstracted chloride from the Ritter-type solvolysis of benzhydryl chloride [13]. The crystal structure of 5Br was also obtained directly from the halide-abstraction reaction (see Supporting Information File 1). These three facts

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• , J = 16.5, 1H), 6.25 (dd, = 6.54, 15.78 Hz, 1H), 5.90–5.79 (m, 1H), 5.22–5.15 (m, 2H), 4.36 (q, J = 5.85, 1H), 2.41 (q, J = 8.94, 2H). Influence of electrode material. Aldehyde variations. Halide variations. Recycling for the allylation of p-anisaldehyde in TBAB/EG DES and Sn electrodes. Tin metal

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• the blue region. This complex then accelerates the oxidative addition of the aryl halide to the metal, which is usually the rate-limiting step for palladium-catalyzed cross-couplings. Based on these results we decided to perform all Negishi reactions under blue light irradiation. With the optimized

• conditions in hand, we proceeded with the investigation of the heteroaryl halide scope in batch (Scheme 3). Thiazoles proved to be challenging substrates typically affording the desired products in moderate yields (2b–h). While 2-chlorothiazole led to the production of 2b in 44% yield, 2-bromo-5

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• pathways Methyltransferases can be classified based on various factors, such as their substrates (small molecule MTs, protein MTs, or RNA/DNA MTs), the atom that accepts the methyl group (oxygen = O-MTs, nitrogen = N-MTs, carbon = C-MTs, sulphur = S-MTs, or halide = H-MTs), metal or cofactor dependence

• atom, describing O-, N-, C-, and S-MTs; halide MTs have not (yet) been identified in RiPP pathways. The enzymes described below are either conventional SAM-dependent MTs or radical SAM (rSAM) MTs; rSAM MTs are one subfamily of the large rSAM enzyme superfamily, which encompasses enzymes catalysing a

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• catalyst/DBPO combinations next (Table 1, entries 5–10), showed that the reaction requires a quaternary ammonium halide containing an easily oxidizable counter anion, i.e., iodide or bromide (Table 1, entries 5 and 7). No product formation was observed in the absence of any catalyst (Table 1, entry 6) or

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

• halogen-bond formation by the linear combination of the % p-orbital character on the halogen and energy of the σ-hole on the halogen-bond donor. Keywords: aryl halide; diarylhalonium; halogen; halogen bond; non-covalent interaction; Introduction Halogen bonding has emerged as an important attractive

• pentafluorophenyl halide series with chloride anion (Scheme 4c, 49–52). A similar trend for decreasing bond length with increasing van der Waals radii has also been observed for some [38], though not all [39], series of chalcogen bonds. Generally, shorter bonds are stronger and longer bonds are weaker, and the

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

• the pyrazole tautomerism [28], the formation of two possible regioisomers, 17 and 18, was anticipated and could be confirmed experimentally. Depending on the employed halide 16, the distribution of the obtained products varied. A considerable excess of the dominating isomer with yields of up to 70

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

• metallaphotoredox catalysis (Scheme 19). Therein, alcohols were activated by the use of NHC salts. This activation facilitated the construction of C–C bonds when combined with aryl halide coupling partners. A diverse array of alcohols and various medicinally important aryl and heteroaryl halides reacted well in

• avoid the use of various halide-based reactants but also opened up C–O bond activations in terms of alcohol and acid functionalizations, choice of reactants, etc. Consequently, in this review, we focused on the advancements in photocatalytic alkyl and acyl radial generation from alcohols and acids. It

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

• 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

• RhCl(PPh3)3 in THF as shown in Scheme 3. In addition, similar reactions using 4-fluorobenzyl bromide (1b) or 4-bromobenzyl bromide (1c) gave the desired dibenzyl products 2b (85%) or 2c (90%) along with 3a in 64% or 54% yield, respectively. Mechanistically, the benzyl halide works as an oxidizing agent

• yields, especially 1,2-dibromoethane was the best oxidant. The reaction proceeded in good yield, even if 0.5 equiv of 1,2-dibromoethane were used in this reaction, as shown in Table 1, entries 7 and 8. However, it has been confirmed that this reaction did not proceed when no alkyl halide was added to the

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• ketones using external halide source [30]. We envisioned that dialkyl bromoalkenes 1 could be used as enol analogs with an improvement in reaction conditions in the presence of I(III) reagents to directly get both symmetrical and unsymmetrical dialkyl bromoketones 2 (Scheme 1c). Recent methods have been

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• use in different fields of chemistry like synthesis [4][5][6][7][8][9], catalysis [10][11][12][13][14] and materials science [15][16][17][18][19][20][21][22][23]. ILs generally consist of an organic cation [24], such as the imidazolium or ammonium ion and an inorganic anion like a halide anion or

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• intramolecular nucleophilic attack of the oxygen to the halide to give intermediate U and subsequent ring-cleavage. The reaction of 3-ketoamide 34a (R3 = Me, R4 = Ph) with 3-chloro-, 3-bromo-, and 3-iodochromone showed that the yields strongly depend on the type of halogen atom located at position 3 of the

• hydrate which reduces significantly its electrophilicity. In case of 3-halochromones, the halide acts as a leaving group during the reaction. For 3-cyanochromones, a nucleophilic attack of chromone-derived hydroxy group to the nitrile was observed in most cases. However, a different reaction was observed

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

• ) greater electrophilicity of the halo compound due to better leaving group ability of the halide ion, (iii) reduced toxicity, presumably due to faster hydrolysis [18], and (iv) easier oxidation of the halide to molecular halogen (E0 = 1.087 V (SHE) for Br2/Br−; E0 = 1.358 V (SHE) for Cl2/Cl−) [19

• redox couple NaBr–NaBrO3 in acidic media [40][41]. Other variations include the system KBr–Oxone® [42]. However, based on a literature review, we concluded that unparalleled efficiency and sustainability can be achieved through the well-established redox equilibria between hydrogen peroxide and halide

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

• carbonylation reaction [81]. Initially it was assumed that the presence of the halide and the NH group could lead to an oligomerization or polymerization reaction, but carrying out the reaction with Pd(CH3CN)2Cl2/dppf as catalyst system and Et3N as the base at 130 °C under 25 bar of CO, they succeeded in the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• discovery by Markovnikov in 1869, who formulated the "Markovnikov rule" as follows: "Experience shows that the halide adds to the least hydrogenated carbon, that is, to the one most susceptible to the influence of other carbon units” [1][2]. In the 1960s and 1970s, various research groups conducted detailed

• chloride metal halide complexes are −6 kJ mol−1 for SnCl4, −8 kJ mol−1 for BiCl3, −9 kJ mol−1 for ZnCl2, −15 kJ mol−1 for CdCl2, −16 kJ mol−1 for FeCl3, and −41 kJ mol−1 for AlCl3. d) Addition of chloride-containing salts (e.g., LiCl) accelerate the reaction. e) Traces of water can increase the rate of the

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

• reaction of diazo compounds mediated by visible light has been reported by the group of Gevorgyan, which achieves the monofunctionalization of alkenes [52]. Inspired by these collective studies, we considered diazo compounds could be a competent activated alkyl halide equivalent to overcome the synthetic