Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• -induced preorganization that enables inner-sphere proton-transfer steps and thereby enforces Z-selectivity. Notably, electrochemical reduction further offers a compelling platform for selective deuterium incorporation, as isotopic labeling can be achieved directly from simple deuterium sources under

• precisely controlled redox conditions. In 2025, the Fu group reported an electrochemical cobalt-catalyzed Z-selective semideuteration of alkynes (Scheme 5A) [99]. This protocol employs inexpensive cobalt salts as catalysts and utilizes D2O and AcOD as practical and efficient deuterium sources. The reaction

• exhibits a broad substrate scope, high efficiency, excellent functional-group tolerance, and consistently high levels of deuterium incorporation (Scheme 5Bi) [100][101]. Notably, the transformation proceeds efficiently with derivatives of biologically active molecules, such as serine and niflumic acid

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• . Radical trapping experiments and deuterium labeling studies supported the involvement of radical intermediates and solvent-derived hydrogen atom transfer steps in the catalytic cycle. This study highlights the dual role of copper as a photocatalyst and coupling catalyst, enabling hydroamination under mild

• smoothly with styrene derivatives 52 to afford the corresponding Markovnikov hydroamination products 53 in moderate to good yields. Mechanistic investigations have suggested that the transformation proceeded via a radical pathway rather than a classical ionic hydroamination process. Deuterium-labeling

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• of further cyclisation (26e) and crucial ring contraction via 1,2-alkyl shift to 26f. Methyl migration and quenching by elimination finally afford epi-isozizaene (26). Investigative efforts into actinomycetes biosynthesis by Dickschat et al. through deuterium labelling revealed another example for a

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• catalyst yields desirable cycloalkenes after oxidative decomplexation in excellent yield. The same reaction with D2 produces a single isomer in which all the deuterium atoms are anti to osmium. Earlier authoritative reviews by Harman provide comprehensive accounts of the rich chemistry accessible through

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• Å (as a proxy for the replacement by deuterium) [20]. Thus, the calculated isotope effect is the sum of the effects of deuteration of the OH and NH positions. However, as isotope effects are transmitted poorly via aliphatic carbon atoms [18], the effect at the phenolic ring can be assumed to stem

• almost entirely from deuteration of the hydroxy group. The good linear fit (R2 = 0.95, Figure 6e) indicates that the isotope effects on the chemical shift values could be calculated accurately. Notably, the two-bond deuterium isotope effect on the 13C chemical shift reflects the strength of the hydrogen

• the polar nature of this functional group. Based on computationally predicted and experimentally determined secondary deuterium isotope effects, we pinpointed the presence of an IMHB in the neutral form of 1, wherein the phenol proton interacts with the lone pair on the secondary amine. The pKa values

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• methyl ester who observed intramolecular proton transfer with partial incorporation of deuterium upon quenching with deuterium oxide. In a different context, the role of the Pd catalyst and the associated ligand was studied in the cross-coupling of the organozinc reagent ent-35 with 3-iodomethylfuran

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• cationic resonance G quickly. The nucleophilic attack of D2O formed H, which underwent dedeuteration and elimination of DI to form 30a with reduction of deuterated water to generate deuteroxyl ions (OD−) and deuterium gas (D2) at the cathode. This method, using iodide salts as electrolyte and redox

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• ]. The experimental studies on the thermal denitrogenation of diazabicyclo[2.1.1]hep-2-ene (DBH, 1) indicate that both the parent compound and its derivatives undergo a concerted elimination of N2 and the inverted product (exo-2) is preferentially formed [55][56]. Deuterium labeling of DBH was employed

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• reaction mixture was stirred at 120 °C for 24 hours, resulting in the formation of 27% of 3a along with 33% of 3a′. To further investigate the role of the solvent in the reaction mechanism, a deuterium-labeling experiment was performed by reacting 1a with 2a in deuterated methanol (CD3OD) under standard

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• still runs smoothly, if the aryl is substituted for cyclohexyl. The proposed mechanism, supported by control experiments, deuterium exchange studies and energy calculations, consists of the following steps: conjugate addition of the carbene to the allenoate, regioselective addition of the resulting

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• L9, and reagents, delivering enantioenriched 2-/3-alkyl-substituted pyrrolidines with excellent regio- and enantioselectivity (up to 97% enantiomeric excess). Radical-clock experiments and deuterium-labeled silane studies revealed that cobalt catalysis proceeded via irreversible Co–H migratory

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

• , providing rapid access to highly enantioenriched organometallic and organosilicon compounds. Mechanistic studies using a deuterium-labeled allylic phosphate revealed that the C–C-bond formation occurs through an SN2'-like process, with attack of the organocopper species at the 3-position of the allylic

• conditions render this method attractive for constructing complex chiral molecular architectures. A plausible mechanistic pathway for this cascade asymmetric hydroboration and hydroallylation of alkynes was proposed based on a series of control experiments, including deuterium-labeling experiments and DFT

• operative, deuterium-labeling studies were conducted using an enantioenriched, isotopically labeled allylic bromide (S)-54 (61:39 er) and 1,1-diborylethane 52a under optimized reaction conditions (Scheme 19a). The resulting product 55 formed with 39:61 E/Z selectivity, indicating an anti-SN2' oxidative

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• (entry 10, Table 1) in deuterated solvents (Scheme 2; for details, see Supporting Information File 1, page S40). Surprisingly, the electrolysis in a 5:1 mixture of MeCN-d3 and water delivered 11d without deuterium incorporation (Scheme 2, reaction 1). In contrast, the formation of deuterated 11d-D was

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

• all of these authors confirmed, after analyzing the position of the deuterium atoms in the final compound, that the methylene unit incorporated into the heterocycle came from DMSO. In the case of pyrazole synthesis, Guo et al. proposed a three-component cascade reaction of enaminones, hydrazines, and

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

• , deuterium labelling, rearrangements on stereodefined substrates, and structural analyses (NMR and X-ray) of the reaction products. RT-NMR-derived data strongly supported a pathway of alkene activation by the iodane, as opposed to the formation of an N-I(III) adduct. The presence of 5-exo-products, with

• support of a deuterium labelling experiment, also ruled out the possibility of an N-activation pathway. Therefore, the proposed mechanism involves BF3-coordinated I(III) iodane forming iodiranium(III) ions with the alkene, followed by diastereo-determining 5-exo-cyclisation. These transiently formed

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• , entries 6–8). When N-propanoyl derivative 4e was used, cyclization proceeded similarly, yielding the corresponding oxazole 5e (Table 3, entry 9). When the reaction was quenched with deuterium oxide instead of acetic acid, monodeuterated oxazole 5a-d1 was obtained (Scheme 2). Based on these experimental

• decarboxylation accompanied by aromatization of the oxazole ring occurred during this process. Thus, protonation occurs, leading to oxazole 5 when the reaction mixture is warmed in the presence of large amounts of proton sources such as acetic acid or deuterium oxide. Although Nagao et al. proposed another

• experiments were conducted in the same way. In the deuteration experiment, the reaction was quenched with deuterium oxide (0.2 mL) instead of acetic acid. The decrease of the integral of the signal of the benzyl proton was confirmed by 1H NMR analysis. Synthesis of polyfunctionalized methane derivatives

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• , 50a–l) axial chirality in remarkable enantiopurities. Mechanistic studies and deuterium labeling experiments have revealed that the reaction proceeds in a stepwise manner without involving a 1,5-H migration process. Based on these findings, the authors have proposed a mechanism wherein the

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

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

• the production of the possible olefinic product n-C8H17CH=CH2. Moreover, when the reaction mixture was quenched with D2O, incorporation of deuterium was observed to give 11a-D in a high yield which allowed us to conclude the possible presence of the C-copper species just before quenching. Our result

• of the reductive elimination very slow, the intermediary Cu(III) species safely existed until the addition of D2O. Because the significant overlap of NMR peaks was observed due to the quite similar structure of 11a and 11a-D, quantitative analysis of the deuterium content of 11a-D was not possible

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• that does not necessitate for NP modification might be desirable. This may include hydrogen–deuterium exchange mass spectrometry (HDX-MS), limited proteolysis-coupled mass spectrometry (LiP–MS), thermal proteome profiling (TPP), cellular thermal shift assay (CETSA), affinity selection-mass spectrometry

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• , Tucson, Arizona, 85721, USA 10.3762/bjoc.20.195 Abstract The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D1]-aldehydes and

• drug-like compounds with synthetic ease [5][6]. In recent years use of deuterium in drug discovery has expanded beyond mechanistic and tracer studies to deuterium incorporation in small molecules in attempts to hijack the deuterium kinetic isotope effect to induce longer drug t1/2 and greater systemic

• exposure [7][8][9]. Herein, we describe applications of deuterium-labeled reagents with MCRs through use of deuterated aldehydes and deuterated isocyanides, an area of study with sparingly few examples. One example by Srivastava obtained a 65% deuterated Passerini product starting from a 65% deuterated

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• viscosity, from 0.89 in H2O to 1.10 mPa⋅s in D2O [42], which is attributed to slow diffusion of micelles within the medium. Furthermore, the rate of H+/D+ exchange between the solvent and the photoswitch will decrease due to the heavier deuterium atoms in D2O, resulting in an effective weakening of the

• purification system. Hydrobromic acid (48%) and deuterium oxide (99.9 atom %) were supplied by Merck. Sample preparation To produce micellar samples, light-responsive PS were shaken with the solvent (50 mM in either H2O or D2O) until homogenous. For samples of higher concentration, AAPTAB was added to water

• Journal of Synchrotron Radiation, distributed under the terms of the Creative Commons Attribution 4.0 International License). SAXS curves for the Z-rich PSS of AAPTAB (50 mM) in (a) water (H2O) and (b) deuterium dioxide (D2O) show changes to the micelle shape and size on X-ray exposure. Fits to the data

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• source in this reaction, a deuterium labelling experiment was conducted (Scheme 2C). Indeed, the deazaalloxazine derivative 6-d with quantitative incorporation of deuterium in C(5) position, was isolated and confirmed by 1H NMR analysis and mass spectrometry (for more details on possible reaction

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

• hydroarylation product was not observed (Scheme 3b). This result strongly supported the involvement of radical intermediates in the present transformation. Next, a deuterium-labeling experiment was conducted to elucidate the H-source of this reaction (Scheme 3c). The reaction of 1a and 2e in MeCN with D2O

• provided the coupling product with 51% deuterium incorporation, indicating that carbanion species would be generated in this reaction and that H2O would serve as a major proton source. Et4NCl may also provide protons to form the coupling product [47]. Taken these results together, the present