Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• equivalents, which is crucial in dual or triple catalytic cycles. The electron-rich carbene center facilitates faster SET processes in photocatalytic reactions. Triazolium-based NHCs exhibit higher oxidative and photochemical stability, making them well-suited for visible-light-driven catalytic

• , Michael additions, cycloadditions, domino reactions, cascade annulations, Diels–Alder reactions, and Michael–Stetter reactions, to name a few [31][32][33][34][35]. Notably, previous reports have demonstrated that the utility of chiral N-heterocyclic carbene (NHC) catalysts permits contracting asymmetric C

• of an acridinium photocatalyst and NaI (10 mol %) as a cocatalyst, affording an innovative method for oxidative carbene catalysis under mild conditions. Previous reports showed that 9-Mes-10-Me-acrydinium (Ered* in T1: +1.45 V vs SCE in CH3CN) exhibited more positive potentials, leading to an

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• vibralactone, a potent inhibitor of pancreatic lipase, is reported. The synthesis of the challenging all-carbon quaternary center within the cyclopentene ring was achieved through intramolecular alkylidene carbene C–H insertion. Keywords: alkylidene carbene; C–H insertion; total synthesis; vibralactone

• lactone 13 through allylic oxidation and cross metathesis. For the construction of the cyclopentene ring, an alkylidene carbene-mediated C–H insertion would be applied [35]. The synthetic route could be traced back to β-lactone 14, which contains two continuous stereogenic centers with trans configuration

• alkylidene carbene. Therefore, we modified the synthetic sequence and opted to construct the five-membered ring prior to β-lactone formation, identifying intermediate 19 as a potentially suitable precursor. From 19, after treatment with lithiotrimethylsilyldiazomethane [45], only tetrahydrofuran 22 was

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• ], ion pairs [15], N-heterocyclic carbene (NHC) catalysts [16][17][18], or thiols [19][20][21] are not covered here but can also be effective for achieving high levels of enantioselectivity in radical reactions. Lewis acid-catalyzed radical reactions In the context of enantioselective radical reactions

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• toward bicyclo[4.3.0]nonane frameworks via geminal carbo-functionalization of 3-siloxy-1,3-dien-7-ynes (Scheme 21) [32]. A stereoselective sequence initiated by 5-exo-dig cyclization and Michael addition under cationic gold catalysis to generate strained bicyclic gold-carbene complex 101, which was

• strategy employed transition metal-catalyzed carbene intermediates to mediate stereoselective cyclization, affording bicyclo[4.3.0]nonane derivatives with configurations distinct from Diels–Alder adducts. In 2013, Alami and co-workers demonstrated catalyst-dependent cycloisomerization of aromatic enynes

• carbazole 113 (Scheme 23, path a). In contrast, the utilization of PtCl4 as a catalyst induced a distinct reaction pathway involving a platinum carbene intermediate 114. This intermediate underwent a different 1,2-alkyl shift, leading to the selective formation of carbazole derivative 115 (Scheme 23, path b

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• Scheme 8 [72], the easily prepared substrate underwent the CBS reduction conditions and protection of the resulting secondary alcohol with TBSCl to afforded silyl ether ketone 90 in 46% yield (two steps, dr = 40:1, 92% ee) [8]. Horner–Wadsworth–Emmons (HWE) reaction of 90 followed by Cu-carbene migratory

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• 22, 14195 Berlin, Germany School of Natural and Environmental Sciences, Newcastle University, Bedson Building, Newcastle upon Tyne, NE1 7RU, UK 10.3762/bjoc.21.153 Abstract Light-mediated methodologies for the reduction of acylazolium species generated during N-heterocyclic carbene (NHC)-catalyzed

• applications, are underway in our laboratory. (a) Combining N-heterocyclic carbene (NHC) organocatalysis with photoredox catalysis for radical–radical coupling reactions. (b) This work: light-mediated reduction of acylimidazolium species 1 with the tertiary amine DIPEA or the simple silane HSiEt3. Initial test

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• imidazole-based N-heterocyclic carbene (NHC)–CuCl complexes [40]. However, their synthesis is often tainted by the use of toxic reagents and solvents. In addition, when o-phenylenediamine reacts with ketones, the common catalytic methods yield benzodiazepine products [41]. In our case the reaction of o

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

• 2016 complemented by a few older works that were deemed powerful and relevant for illustrating a given reaction mode. Chapter 1 covers strategies for the oxetane ring formation including substitutions, cycloadditions, ring-size manipulations and carbene insertions. Chapter 2 details chemical

• enantioselectivities. In 2018, Scheidt and colleagues disclosed the first N-heterocyclic carbene (NHC)-catalysed [2 + 2] annulation between trifluoromethyl ketones and γ-substituted allenoates (Scheme 25a) [68]. The resulting 2-alkylideneoxetane products 95 were generally obtained in >90% yields and good

• 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 oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• for constructing quaternary carbon centers in oxindoles via an N-heterocyclic carbene (NHC)-catalyzed intermolecular Heck-type alkyl radical addition and annulation reaction (Scheme 47) [28]. The reaction proceeds through a redox-neutral mechanism, where the NHC catalyst serves a dual role as both a

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• construction, alkyne hydrogenation, ylide and carbene reaction, metathesis, E/Z isomerization, and other methods, including Cα and Cβ functionalizations. Preparing various functional group-tethered aromatic groups can be achieved by directly installing an aromatic group via cross-coupling reactions and other

• (2022) investigated the visible-light-mediated amidation of cinnamic acid (7) by using ethyl 2-diazoacetate and acetonitrile to give its corresponding amide 103 in excellent yield (Scheme 32) [29]. The reactive free carbene 104 was released upon light exposure of the diazo ester leading to the nitrilium

• -workers (2019) reported an enantioselective esterification via oxidative N-heterocyclic carbene (NHC)-catalyzed phthalaldehyde activation to form azolium ester intermediate 147 to give the chiral phthalidyl ester 146 with excellent enantiomeric ratio (Scheme 45B) [85]. Additionally, the reaction capacity

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• was utilized to transform enamine 18 and propargyl ester 19 into 1-azaspiro[4.4]nonane 20 with high diastereoselectivity. Notably, the combination of an N-heterocyclic carbene gold catalyst and a silver salt AgSbF6 was found to be essential in guaranteeing the reactivity of the alkyne partner

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

• , Koenigs, and co-workers demonstrated solvent-controlled bifurcation in the light-driven reactivity of cyclic diazo imides 41 with thiols 42, unveiling two mechanistically distinct pathways (Scheme 11) [40]. In dichloromethane (DCM), the reaction proceeds via a carbene intermediate, enabling cascade C(sp2

• )–H functionalization/thiolation to deliver indane-fused pyrrolidines 43 in excellent yields (up to 92%). Strikingly, switching the solvent to acetonitrile completely suppresses carbene formation under identical conditions, redirecting the pathway toward an unconventional diazo reduction wherein aryl

• thiols act as stoichiometric reductants. Mechanistic insights, elucidated through control experiments and DFT calculations, revealed that photoexcitation of diazo imide 41 triggers nitrogen extrusion (ΔG‡ = +10.0 kcal·mol−1), generating the triplet carbene intermediate Int-45. In DCM, this species

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

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

• their exploration of phosphoramidite ligands with various organometallic nucleophiles [24][25]. The field was further advanced by the research group of Hoveyda, who made substantial contributions by introducing bidentate N-heterocyclic carbene (NHC)-based chiral ligands, achieving high selectivity with

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

• researchers identified high-affinity binding sites for the ligand within the Fc domain. This structural analysis allowed precise determination of amino acid residue positions and orientations. Upon photoirradiation, the pLeu within the pFcBP generated a carbene from the diazirine moiety. This transformation

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• processes with low catalyst loading. It involves the kinetic resolution of alcohols, amines, and esters using chiral phosphoric acids [6][7][8][9][10][11][12][13] and sulfoximines with enals using chiral N-heterocyclic carbene (NHC) catalysts [14]. Additionally, these processes have been conducted using

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

• acetone, allowing the pre-activation of the ruthenium complex with the successive release of an N-heterocyclic carbene ligand and a chlorine atom, which are replaced by two acetone molecules to form compound 2. Simultaneously, excitation of the osmium(II) complex in the red region (660 nm) decreases its

• catalysis for carbene transfer reactions and radical-based functionalizations [41]. In another study by Derksen et al., thiaporphyrins were introduced as highly effective catalysts for red-light-mediated photoreductive dehalogenation [42]. These thiophene-modified porphyrins exhibit excellent absorption

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• organocatalytic reactions are discussed according to the dominant catalyst activation mode. For covalent organocatalysis, the typical enamine and iminium modes are presented, followed by N-heterocyclic carbene-catalyzed reactions. The bulk of the review is devoted to non-covalent activation, where chiral Brønsted

• axially chiral N-aryl succinimides 54. The tentative mechanism comprises the formation of the Breslow intermediate Int-31 from the catalyst carbene and aldehyde 52, which then adds to the electron-deficient double bond of maleimide giving rise to Int-32 (Scheme 17). Chi and co-workers developed an

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

• -workers reported a dihydroquinine-derived squaramide-catalyzed (3 + 2) cycloaddition reaction of isocyanoacetates 26 and saccharin-derived 1-azadienes 14 [32]. In this work, the azadiene works as a C2 synthon, while the isocyanoacetate, bearing a protected carboxylic acid and a carbene-like divalent

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• situation. Dibenzyl ester 11c was prepared using traditional activation of carboxylic acid 6a, although the yield was only 23%. A higher yield of the branched ester 11d (86%, as a mixture of diastereomers) was obtained by carbene insertion, generated by blue LED irradiation of methyl 2-diazo-2-phenylacetate

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• and a photosensitizer, facilitating photoinduced electron transfer (PET) to form the active cation radical B, and intersystem crossing (ISC) for energy transfer to generate the triplet carbene C. Radical B then reacted with biradical C, producing the new radical D, which accepted an electron from the

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

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• )triphenylphosphonium salt 6 and (iodomethyl)triphenyl-phosphonium salt 7. Homolytic or heterolytic scission of the I–C(ylid) bond with loss of ArI (path a) would result in a carbene, though it is unclear how this would transform to compound 6. Alternatively, scission of the I–C(Ar) bond with loss of benzyne (path b

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

• -depleting sulfur dioxide as side products [46][47]. Later, Ichikawa and co-workers established the release of difluorocarbene from TFDA with catalytic amounts of an N-heterocyclic carbene and a base (Scheme 1C) [29][48][49]. In these reactions, difluoromethyl enol ethers were obtained, which were

• reaction time of 60 min, both reducing and increasing the amount of 2 (from initially used 2.0 equiv to 1.5 equiv and 3.0 equiv, respectively) reduced the yield of 3a by about 10% (Table 1, entries 3–5). Probably, with less carbene precursor the amount of generated difluorocarbene was insufficient, and