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

• , the Shu group developed a catalyst-controlled regioselective and enantioselective hydroamination reaction of electron-deficient alkenes (Scheme 7) [30]. By efficiently regulating the regioselectivity and enantioselectivity of alkene 23 hydrometallation through catalytic systems, they overcame the

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• , Germany 10.3762/bjoc.21.69 Abstract The photoactivation of organic molecules via energy transfer (EnT) catalysis is often limited to conjugated systems that have low-energy triplet excited states, with simple alkenes remaining an intractable challenge. The ability to address this limitation, using high

• ). Pioneering studies have leveraged this platform with great effect, typically invoking π→π* transitions of conjugated alkenes to lower the bond order and generate a triplet diradical, primed for further reactivity. This key intermediate is pivotal in a plenum of synthetic transformations including geometric

• isomerization of alkenes [18][19], [2 + 2] cycloadditions [20][21][22][23][24], and dearomative [4 + 2] cycloadditions [25][26][27]. When considering conjugated alkenes, the triplet excited state energy and excited state lifetime are intrinsically linked to the degree of conjugation and substitution of a

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• catalytic hydrocyanation of alkenes [22], including the industrially relevant DuPont adiponitrile process from 1,3-butadiene using nickel catalysts [23], the hydrocyanation of allenes to produce functionalized β,γ-unsaturated nitriles with quaternary carbon centers has not been investigated extensively [24

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

• amides with electron-withdrawing or electron-donating groups on their aromatic ring, producing products with yields ranging from 51% to 82%. In 2023, Lei and co-workers [47] reported an electrochemical C–P bond formation via a coupling reaction of C–H bonds of alkynes, alkenes, and aryl compounds with

• followed by treatment with acridine to give the corresponding coupling product (Scheme 6). Vinylphosphonates have many applications in pharmaceutical, agricultural, and industrial processes. Zhang et al. [51] reported a novel electrochemical C–P coupling of specific alkenes with different types of

• and copper foam (CF) as a cathode at a constant current of 14 mA. Experiments confirmed that the trace amount of copper dissolved from the cathode had no catalytic effect on the reaction. The reaction proceeded via anodic oxidation of diphenylphosphine followed by a reaction with alkenes to give

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• rearrangement under mild conditions [6], and the Nazarov-type electrocyclization of alkenyl aryl carbinols [7]. Exploiting the ease with which calcium forms hydrides, hydrogenation of aldimines, transfer hydrogenation of alkenes, and even deuteration of benzene by an SNAr mechanism, have been recently achieved

• transfer hydrocyanation of alkenes proceeds via (boron) isocyanides [50]. If calcium cyanide would be preferred over isocyanide, hydrocyanation would hardly be possible. A principally conceivable "hydroisocyanation" of hydrazone is therefore precluded. The relative stability of alkaline earth metal

• that might similarly occur also in related addition reactions of alkenes, for example. After 11E had reacted with TMSCN, adduct 13 forms, 3.8 kcal·mol−1 more stable than the competing unreactive adduct obtained from "Z" conformation. Outside from the catalytic cycle, 12 could be further hydrolyzed in a

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

• regioselectivity (SN2/SN2' = >99:1). The reaction with 3-methylbut-2-en-1-yl bromide (15) was particularly noteworthy, as it exhibited superior selectivity compared to the corresponding phosphates. The high efficiency of this protocol was demonstrated through the synthesis of various functionalized alkenes with

• -trifluoromethylalkenes 38 with hydrosilanes and allylic chlorides 40 (Scheme 14b) [55]. In their work, a chiral α-CF3 alkylcopper intermediate 39 was formed through the regio- and enantioselective hydrocupration of electron-deficient alkenes 38 with an in situ-generated CuH species. Subsequent electrophilic trapping of

• showed a broad scope, tolerating both 1,1-diborylalkanes with N-tosyl-protected amines and TBS-protected alcohols, as well as substrates containing alkenes and alkynes. Various allylic bromides 46 with electron-rich and electron-deficient aryl substituents worked well, giving homoallylic boronic esters

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• particularly useful and important tool in which azides and other dipolar species engage with reactive alkenes and alkynes on non-canonical amino acids [20]. Transition-metal-mediated processes, including metathesis reactions, aryl cross-coupling reactions, and conjugate addition reactions with dehydroalanine

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

• –Alder reaction between an imine and an alkene (Scheme 6). Very successfully, the multicomponent version of the Povarov reaction using aldehydes, anilines, and alkenes has been explored in a three-component cascade reaction to quinolines [28][29][30][31] (Scheme 6). Furthermore, protocols have been

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• benefits of the photomechanochemical approach in the field of synthesis [77]. Specifically, they developed photomechanochemical conditions for the atom-transfer-radical addition (ATRA) of sulfonyl chlorides to alkenes, pinacol coupling of carbonyl compounds, decarboxylative acylation, and photocatalyzed [2

• instead of 2 h in a row) proved beneficial to minimize heat accumulation resulting in product decomposition. Next, the authors proved the generality of mechanoluminescence by performing the sulfonylation of alkenes via EDA-complexes photochemistry (Scheme 12B). Thus, when a mixture of 1,1-diphenylethylene

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

• the substrate, an activated ester 25, subsequently generating carbon-centered radicals without the need for sacrificial electron donors via a decarboxylation process. In reacting with electron-deficient alkenes or alkynes 26, these radicals further yield tetralin and dialin moieties 27, respectively

• redox properties similar to those of squaraine derivatives, enabling key transformations such as the cyclization of anilines with maleimides and the reduction of Umemoto salts for trifluoromethylation of alkenes. With an excited-state reduction potential around 0.80 V, 46 demonstrates the capability to

• , Goddard et al. have developed a second generation of cyanin dyes. For example, in the case of the photocatalyzed trifluoromethylation of alkenes, it has been shown that the stability of the photocatalyst was crucial for achieving efficient and faster conversion. In their study, the authors have reported

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• reactions of isatins with alkyl acrylates, acrylonitrile, and other activated alkenes [26][27][28][29]. Due to the stronger electron-withdrawing effect of the oxindole motif, MBH carbonates of isatins showed higher reactivity than that of the normal MBH carbonates of normal ketones [30][31][32][33][34][35

• very different to that of the above mentioned reactions of MBH nitriles and formates of isatins. It has been reported that triphenylphosphine can catalyze the cycloaddition reaction of MBH carbonates of isatins with some activated alkenes to give diverse spirooxindoles [38][39][40][41]. The reaction of

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• CF2HCO2H or PhCF2COOH, along with benzimidazoles bearing unactivated alkenes and PhI(OAc)2 as substrates, and proceeded without the need of any base, metal catalyst, photocatalyst or additive. In total, 24 examples were examined, and all of them successfully underwent cyclization reaction to produce the

• groups have reported the direct difluoromethylation/cyclization reaction of benzimidazoles with alkenes for the syntheses of difluoromethylated tricyclic benzimidazoles to date. For example, in 2023, Chen and co-workers pioneered an electrochemical approach for the difluoromethylation and cyclization

• reaction of unactivated alkenes within benzimidazole molecules using CF2HSO2Na [18]. Subsequently, in 2024, Jin [19] and Yang [20] developed visible light-induced difluoromethylation strategies for unactivated alkenes within benzimidazoles using different CF2H sources (CF2HSO2Na and ([Ph3PCF2H]+Br

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

• area of medicinal chemistry [93][94][95][96][97]. In 2018, Buchwald and co-workers unveiled the enantioselective synthesis of benzylic amines through the asymmetric Markovnikov hydroamidation of alkenes utilizing diphenylsilane in copper catalysis under mild reaction conditions [98]. Dioxazolones, as

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

• bromine radical attack that leads to the formation of a cationic brominated copper complex 77. Anodic oxidation and subsequent proton transfer provide the desired product 73 and regenerate the copper catalyst. Olefin addition Hydrofunctionalization and difunctionalization of alkenes are valuable methods

• for synthesizing complex molecules from alkenes, a readily available feedstock [65]. Particularly, transition-metal-catalyzed difunctionalization has recently been extensively investigated, and asymmetric reactions have been developed [66]. Many approaches rely on the addition of a radical species to

• group across alkenes 27. This reaction is applicable not only to a wide range of terminal styrenes but also to internal alkenylarenes, enynes, and allenes, providing enantioenriched products in good yields with high enantioselectivities. This reaction involves Co-catalyzed HAT and Cu-catalyzed

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• -(trifluoromethyl)-1-alkenes strongly interact with electron-rich zero-valent nickel species to form nickelacyclopropanes C [15][16][17]. These intermediates enable C–F bond activation through the formation of nickelacyclopentenes D with alkynes, followed by β-fluorine elimination, leading to defluorinative

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

• -difunctionalization of alkenes carried out with carbazates (N-aminocarbamates) and (hetero)arene nucleophiles or amines exploiting N-(tert-butyl)-N-fluoro-3,5-bis(trifluoromethyl)benzenesulfonamide (NFBS) as intermolecular hydrogen-atom-transfer reagent results in alkylarylation processes (Scheme 5) [19]. The

• , hydrazines and alkenes with Cu(OTf)2 (20 mol %) in CH2Cl2 at reflux is a useful tool to access substituted 4,5-dihydropyrazoles 31 (Scheme 23) [40]. The products reasonably result from a Mannich/cyclization/oxidative transformation of the substrates in which Cu(OTf)2 is involved in more steps. The reaction

• multicomponent synthesis of acyclic and heteropolycyclic systems under copper(II) triflate catalysis are reported. Using alkenes and alkynes as substrates, various types of reactions were considered, including hydroamination, condensation, cross-coupling, C–H functionalization, cycloaddition, aza-Diels–Alder

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• the field, other dienes bearing two nitrogen atoms in their structure such as 1,3-azadienes or azo-alkenes are also included. On the contrary, asymmetric cyclizations involving aza-ortho-quinone intermediates and in situ-formed 1-azadienes were excluded as they have been discussed in other recent

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• ]-cycloaddition reaction between electron-poor 1,2-diaza-1,3-dienes and electron-poor alkenes in refluxing acetonitrile was reported leading to various substituted tetrahydropyridazines in 17–78% yields (Scheme 1c) [26][27]. Nevertheless, these methods are neither relevant for the synthesis of 1 nor appropriate

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

• , the intramolecular HVI-mediated halocyclisation of alkenes using carbon, oxygen, nitrogen or sulfur nucleophiles. Herein, we describe the examples reported in the literature, which are organised by the different halogens involved and the internal nucleophiles. Keywords: cyclisation; halogenation

• ; heterocycles; hypervalent iodine; oxidation; Introduction Halogenated carbocyclic and heterocyclic compounds are present in many active pharmaceutical ingredients [1][2]. The intramolecular halocyclisation of alkenes mediated by HVI(III) reagents allow access to a range of halogenated cyclic scaffolds in a

• 4 [9][10] (Figure 1). Halogenated cyclised structures have also been found to exhibit medicinal and pharmaceutical properties, including antibacterial [11], antibiotic [12], and enzyme inhibition [13] among others. The general mechanism for the HVI-mediated halocyclisation of alkenes proceeds

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

• formation of peroxide 9. The enantioselective peroxidation of alkenes 10 with TBHP with the formation of the optically active products 11 was carried out in good yields and low ee by the use of in situ-generated chiral bisoxazoline–copper(I) complexes (Scheme 7) [43]. Studying the oxidation of α-pinene (12

• alkenes 41 was disclosed (Scheme 17) [59]. The target 6-trifluoromethyl peroxides 42 were synthesized in good yields under mild conditions. The electrophilic CF3 radical A, generated from CF3SO2Na through single-electron oxidation by using Mnn/TBHP system, is captured by the carbon–carbon double bond to

• –peroxidation of unsaturated alkenes 43 using AgSCF3 and TBHP was realized in the presence of the copper catalyst (Scheme 18) [60]. The radical trifluoromethylthiolation of alkenes 43 triggers a 1,5-HAT and further recombination of the generated C-centered radical with the tert-butylperoxy radical to afford the

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• , alkenes) and halogens allowing an array of post-functionalization reactions. Finally, the trifluoromethylthiolation of molecules derived from compounds of interest was achieved to illustrate the synthetic utility of the method. Hence, the desired products 2v–x were efficiently isolated. To get more

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

• as heteroconjugated alkenes with difluorocarbene to give 2,2-difluoro-2,3-dihydrofurans [50] remained unsuccessful (Scheme S2 in Supporting Information File 1). Two mechanisms have been proposed for the difluoromethylation of ketones, as illustrated in Scheme 4A. In both cases, the process begins

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• )alkenes and -phenanthrenes [78]; yet, adjacent hindrance is not a problem in this case. Clearly, more work is required on the Suzuki–Miyaura coupling of molecules with sterically demanding ‘pockets’ with opposing and adjacent hindrance. In conclusion, a library of arm-extended dodecasubstituted porphyrins

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

• 350100, China 10.3762/bjoc.20.232 Abstract The catalytic (asymmetric) allylation and propargylation have been established as powerful strategies allowing access to enantioenriched α-chiral alkenes and alkynes. In this context, combining allylic and propargylic substitutions offers new opportunities to

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

• Sonogashira cross-coupling to exploit the unique structure of multihalogenated fluorovinyl ethers 1 for the synthesis of many kinds of fluoroalkenes 2 and fluoroenynes 3 in moderate to high yields. The synthesized alkenes 2 still possess reactive chlorine atoms and phenoxy groups. Thus, new multisubstituted