Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• anode and phosphonate anion at the cathode (Scheme 12). The C(sp2)–X in aryl and vinyl halides is suitable in organic coupling reactions that are usually active in electrochemical environments. The use of combined electrodes is one of the creative methods in electrosynthesis processes. Léonel et al. [57

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• fluorophores also exhibited favorable solubility compared to the other functionalizations which is a critical aspect for applications in the cell. We also note that primary alkyl halides, and in particular, the mesyloxy alkyl handles presented here, are relatively underexplored for covalent labeling of nucleic

• acids. Rather, halides with enhanced electrophilic potency, such as α-halocarbonyls [14][15][16], nitrogen (half-)mustards [17][18], or epoxides [19][20], Michael acceptors [17], carbamates [17], imidazolides [17], squarates [17], and diaziridines [17] (the latter requiring photoactivation) have been

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• reversed by adding zinc halides (Scheme 4). When treated with allylic phosphates 17 in the presence of ZnCl₂, these copper reagents 14 showed a dramatic shift in selectivity, favoring SN2' substitution. This exceptional reversed regioselectivity likely occurs through the in situ formation of copper–zinc

• including s-BuLi, n-BuLi, and PhLi. The optimized protocol, employing CuCN as a catalyst, enabled efficient coupling between t-BuLi-activated complexes 10 and allylic halides 11, furnishing products 12 with complete retention of stereochemistry and high yields (Scheme 7). The method's versatility and

• to the parent allyl group, a variety of 2-substituted electrophiles 31 could be applied. These included those bearing alkyl groups of varying steric demand, halides, and both electron-rich and electron-poor aryl substituents. The olefin coupling partner scope was equally impressive, tolerating

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

• with bis(pinacolato)diboron did not lead to the formation of the pinacolborane-substituted N-acetyl diazocine 18. Accordingly, the Suzuki–Miyaura reaction with inversed roles between N-acetyl diazocine boronic acid pinacol ester and aryl or alkyl halides could not be investigated. The Buchwald–Hartwig

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• highly electrophilic warheads otherwise typically employed in RNA-small molecule crosslinking [18][19][20][21]. Instead, primary alkyl halides (or mesylates, Scheme 1, in particular compounds 3a, 3b and 4c) were found to be potent yet mild alkylators that minimize off-target reactivity, while providing

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

• , however, are used synonymously owing to their same participating property and the same Zemplén deprotection strategy [87]. A recent study showed the use of modified Zemplén conditions to synthesise deacetylated methyl β-glycopyranosides directly from per-O-acetylated α-glycosyl halides using a

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

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• olefin addition reactions [20] conducted by various research groups, contributed to this area of research. Recently, the coupling reactions of C(sp3)-based electrophiles were explored using dual photoredox and copper catalysis, achieving selective radical coupling reactions involving alkyl halides [21

• decreasing the oxidation potential. A range of functional groups, such as halides, ethers, and heterocycles, were tolerated well, yielding the corresponding enantioenriched products 14 with high enantioselectivity in the presence of chiral bisoxazoline ligand L2. A possible mechanism is depicted in Figure 5

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• alkyltrifluoroborate into its corresponding alkyl radical. o-Halo-substituted aryl selenides and sulfides 13 can be achieved by a three-component coupling reaction performed with an aryne precursor, potassium halides and electrophilic chalcogen species as reactants, in the presence of Cu(OTf)2 (Scheme 10) [23]. Under

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

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• , alkyl radicals have been produced from alkyl halides, using azobisisobutyronitrile (AIBN) as initiator, promoting a tin-mediated XAT (Figure 1a) [8][9]. However, tin-based compounds are highly toxic and require harsh conditions for the initiation event. Fortunately, a renaissance in the field of

• photocatalytic activation (Figure 1b) [17][18][19][20][21]. A photocatalytic HAT or SET generates the corresponding boryl, α-amino or silyl radical, which can abstract a halogen atom from alkyl halides to form the corresponding alkyl radical. However, the use of TTMS as a XAT reagent had already been established

• photocatalyst (Figure 1d) [25]. Noël et al. [26] have further extended this approach to include alkyl bromides (Figure 1e) [26]. Despite the effectiveness of the photolysis, benzophenone derivatives have also been shown to enhance the productivity of silane-mediated conjugate additions, using alkyl halides [27

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

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• giving a stabilized benzyl radical D, which recombines with tert-butylperoxy radical C to give the target product 179. Later, this approach was modified and extended to various alkyl halides. Diverse α-peroxy-β-substituted ethylbenzene products 181 were prepared from styrenes 180, TBHP and alkyl halides

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

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• organolithium reagents, thus limiting functional-group tolerance [11][12][13]. By contrast, heteroleptic (mixed) alkylzinc species (i.e., RZnX) are readily available and can typically be prepared from alkyl halides by direct insertion of metallic zinc into the carbon–halogen bond [14][15][16][17][18][19][20][21

• , we reasoned that replacing alkyl iodides by alkyl bromides could be relevant to the field due to interesting assets such as better availability and lower cost of the parent alkyl halides. Results and Discussion We investigated new conditions that would allow for the synthesis of mixed alkylzinc

• 16 h at 80 °C (Table 1, entry 2). However, its suitability in the multicomponent coupling with an amine and an aldehyde still had to be demonstrated as there was no precedent for such a Mannich multicomponent coupling involving nonstabilized organozinc halides using THF or 2-MeTHF as solvent. To our

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• reported over the years (Figure 2) [2]. Conventionally, benzophenones are synthesized by Friedel–Crafts acylation of benzoyl halides and aromatic compounds. However, the regioselectivity of Friedel–Crafts benzoylation at the desired position is difficult to control [9]. On the other hand, 2

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

• cathodic reduction and to prevent the reoxidation of the reduced SO2 at the anode, a divided cell setup is required (Scheme 12). C–H bond halogenation: Aryl and alkyl halides are important synthetic building blocks for cross-coupling reactions as well as bioactive molecules with applications in

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

• halogenated pyrans reveals deviation in the intra-annular torsion angles arising from repulsion between the axial fluorine at C2 and the axial halogen at C4, which increases with the size of the halogen at C4 (F < Cl < Br < I). Crystal packing arrangements of pyran inter-halides show hydrogen bond acceptor

• chiral halides: F, Cl, Br, I) [19]. Only a handful of natural product syntheses have been reported [20][21], despite the promising biological activity of these unique inter-halides [22]. For our part, we recently reported the synthesis of contiguous inter-halide-bearing stereocenters using a Chiron

• approach from levoglucosan 1 (Figure 1a) [23]. Allopyranose inter-halides 4 incorporating the 2,3-cis, 3,4-cis relationship for the halogens were prepared via intermediates 2 and 3 from levoglucosan (1). Compounds 4 were the starting point to complex 2,3,4-trihalohexanetriols and 2,3,4,5

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• compounds from alkenes and DDPyOCF3, more precisely to α-trifluoromethoxylated, β-phenylselenylated compounds. Results and Discussion The electrophilic addition of phenylselenyl halides to alkenes to form a selenonium intermediate that can be intercepted by an external nucleophile is a well-known method to

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• shorter period possibly because of its significantly high electrophilicity by the attachment of three strongly electron-withdrawing moieties. Reactions of (E)-3-Rf-2,3-epoxypropanoates 2 with amines, thiols, and metal halides Because the epoxide ring opening is known to occur in an SN2 fashion, compounds

• executed at −78 °C under the action of LDA [29]. Moreover, by using the epoxyester 2b as the representative substrate, clarification of its reactivity was carried out by mixing with 1) heteronucleophiles like amines, thiols, and magnesium halides, 2) softer carbon nucleophiles such as malonates, and 3

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

• obtained: in a titration study by Mayer and Legault it was determined that cyclic five-membered DAI salts, so-called iodolium compounds, are significantly stronger Lewis acids than their less-stable acyclic counterparts [12]. By using the activation of alkyl halides as a benchmark, our group later reported

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• diarylacetic acids from diarylmethanol species and carbon dioxide without transformation of the hydroxy group into appropriate leaving groups, such as halides and esters including carbonates. Keywords: C(sp3)–O bond cleavage; diarylacetic acid; diarylmethanol; electrochemical reduction; fixation of carbon

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

• product, although in this case, reduction of the nitro group to an amino group was observed and the resulting 4-aminobenzaldehyde is likely too electron-rich to undergo allylation. The use of other halides was also explored (Table 3). Switching to allyl chloride (Table 3, entry 2) did result in partial

• more substituted end (gamma addition) was the major product in both cases, although alpha addition was also observed. In the case of crotyl bromide, no diastereoselectivity was noted for the gamma product. Non-allylic halides such as benzyl bromide, propargyl bromide, and ethyl bromoacetate (Table 3