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

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

• , and advanced optical and energy materials. Review Visible-light-driven NHC/4CzIPN-catalyzed reactions Recently, Shu and co-workers developed a direct and innovative preparation of highly functionalized aryl amide derivatives 3 from aryl aldehydes 1 and substituted imines 2 under mild conditions in the

• presence of NHC (20 mol %), 4CzIPN (2 mol %) under mild conditions, producing corresponding unsymmetrical ketone derivatives 8 in up to 95% yield. An Ir-based photocatalyst was initially selected because its excited state is a strong oxidant (E1/2[Ir*III/II] = +1.21 V). Although 4-ethylanisole exhibits a

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• the formation of inter- or intramolecular carbon–carbon bonds under mild conditions [9][10][11][12], and strategically applied this method for the divergent syntheses of some natural products [13][14][15][16][17]. Herein, we report our recent advance to a total synthesis of (+)-aglacin B (2), which

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• their subsequent reaction with O-nucleophiles in the second chamber. The method is easy to setup, control and gives access to new haloacetimidates under mild conditions, similar to the ones used for the synthesis of the more commonly used trichloroacetimidates. Keywords: gaseous reagents; glycosyl

• [14][15][16][17]. Recently, 2,2,2-trifluoroacetaldehyde O-(aryl)oxime has been introduced as a precursor for trifluoroacetonitrile allowing to work under mild conditions at room temperature (Figure 1) [18]. Whether one prepares a precursor or the actual reagent, a separate setup is needed and hence

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• aldehyde 53 [39] (Scheme 10). The key steps in this synthesis are based on an asymmetric rhodium-catalyzed [4 + 2] cycloaddition reaction [40], followed by a unique benzilic acid-type rearrangement under very mild conditions [41]. A step-by-step mechanism for the benzilic acid-type rearrangement of

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• –Yang cyclization and related photoredox reactions, owing to their ability to undergo selective activation under mild conditions (e.g., long-wavelength irradiation) – a feature that minimizes competing fragmentation pathways. Notably, different dicarbonyl substrates exhibit distinct reactivity patterns

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

• substrates or organometallic complexes upon photoexcitation has enabled the synthetic community to access reactive open-shell species under very mild conditions. The ability of excited photocatalysts to induce other reagents, substrates, or other catalysts to participate in new activation modes makes them a

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

• yielded A+, which was then trapped by MeCN/H2O to form the CF3-enamide intermediate B. The subsequent cyclization/oxidation of B offered oxazoline radical intermediate C, which was transformed to the target 36a through anodic oxidation/deprotonation. This transformation, implementing under mild conditions

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

• rapidly under mild conditions. The catalyst 1 oxidizes the vicinal diols to the corresponding hydroxy ketones faster than other alcohols. Primary alcohols and 1,5-diols are oxidized to yield secondary alcohols and cyclic lactones, respectively (Scheme 30). A high chemo- and regioselectivity was observed

• furfural to succinic acid in 88% yield under mild conditions using modified hydrophilic acidic metal-free graphene oxide (GO) as solid acid catalyst and H2O2 as an oxidant [151]. The suitable acidity of the SO3H group on the graphene oxide support is crucial for the selectivity of the oxidation. The use of

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

• chemoselectivity for cysteine alkylation under mild conditions, for example, BCB-ibrutinib [28] (Scheme 1c). BCB is also used as a precursor to byciclo[1.1.1]pentanes, which are valuable motifs in drug design [19][20][29][30][31][32][33], such as BCP-darapladib (Scheme 1c) [30][31][34][35]. Housanes are versatile

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• genus) are generally operated in mild conditions achieving relatively high yield and enantioselectivity. However, due to the intrinsic structural limitations of lipases, accessing the desired enantiomer requires laborious screening of enzymes. In the case of transition-metal-catalyzed acylations, the

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• this shortcoming, it is essential to use monosaccharide building blocks bearing temporary protecting groups that can be selectively and sequentially removed under mild conditions. Such an approach ensures compatibility with sensitive functionalities and enables the effective incorporation of 1,1

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• CyreneTM, as a biomass-originated polar aprotic solvent, could be utilized as an alternative reaction medium for one-pot copper(I)-catalyzed azide–alkyne cycloaddition (click or CuAAC) reactions, for the synthesis of various 1,2,3-triazoles under mild conditions. Nineteen products involving N-substituted-4

• -triazoles in a less toxic and recyclable medium could further control and reduce the environmental impacts of this synthetically very important transformation. Herein, we report a study on the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in CyreneTM under mild conditions. Results and

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• enaminones. This transformation is simple, straightforward, and proceeds under mild conditions. Results and Discussion The initial challenge in achieving the desired reactivity was the activation of the unsaturated system towards the nucleophilic addition of the amine. The most common strategy to increase

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• diaryliodonium salts under photoredox conditions has been proposed for the first time. The suggested procedure allows preparing a broad range of benzamides using both symmetric and unsymmetric diaryliodonium salts under mild conditions. A plausible mechanism for the reaction and the selectivity of aryl transfer

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• , who focus on the preparation of phenethylamines and phenylisopropylamines via reduction of substituted β-nitrostyrenes using a system of sodium borohydride and copper(II) chloride [9]. The transformations are performed in one pot and proceed under mild conditions. The β-nitrostyrene products could be

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• to identify mild conditions for the Cu-catalysed aerobic C–H amination in absence of acid, base or co-catalyst additives. As described in Table 1, we explored the effects of different solvents and copper species, and preliminary reactions were conducted with Cu(II) salts, with reference to reaction

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

• , amides or esters and occurs under very mild conditions that are also suitable for a late-stage functionalisation of complex molecules. The transformation is based on an H-atom transfer to photochemically oxidised quinuclidine followed by an annulation of the resulting ketyl radical 32 with

• epoxide-opening cyclisation for the oxetane formation (Scheme 11b) [45]. The highest yield was obtained for the PhSH/I2 10:1 activator under unusually mild conditions – the authors believed it is due to the oxa-bridge which facilitates the Lewis acid coordination. In 2001, Rousseau and colleagues reported

• lead to another ring expansion producing tetrahydrofurans 108 [73]. In 2022, Zhu et al. employed this strategy in their synthesis of α,α-difluoro(arylthio)methyloxetanes 110 using an excess of the sulphoxonium ylide under very mild conditions (Scheme 27), most likely enabled by the high

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

• quinolinone products. Beyond electrochemical protocols, photochemical activation – particularly visible-light photoredox catalysis – has become a powerful and sustainable strategy for generating carbon radicals under mild conditions. In 2023, Fan’s group discovered a radical cyclization of N-arylacrylamides

• mild conditions, utilizing blue LED light (440–450 nm) as the light source, and achieved good yields ranging from 44% to 99%. The substrate scope was thoroughly explored, demonstrating broad compatibility with various functional groups. Both electron-donating (e.g., methyl, isopropyl, tert-butyl) (78a

• cascade cyclization reaction for synthesizing perfluorinated oxindoles via an AIBN-mediated process was introduced. The reaction utilized N-arylacrylamides and commercially available perfluoroalkyl iodides as substrates, achieving high yields of products 80 under mild conditions (Scheme 41) [25]. The

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

• a regioselective manner. From tetracyclic compound 11, a one-pot facial and regioselective hydroboration/amide reduction followed by oxidation produced (+)-lycoposerramine Q, which was then converted to (+)-fawcettidine by Ley oxidation. Alternatively, hydroboration of 11 in mild conditions without

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• ester 29 gave pyrrolo-β-carboline 30 in excellent yield (Scheme 7). Our attempts for the selective saturation of the pyrrole ring of 30 by catalytic reduction were unsuccessful. When the hydrogenation was carried out under mild conditions (ambient temperature, 15 bar H2) in the presence of PtO2.H2O

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• ) triflate-catalyzed post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds is reported offering high yields (up to 98%) under mild conditions. The synthetic sequence involves the Ugi four-component reaction (U4CR) of pyrazole-3-carbaldehydes, primary amines, 3-substituted propiolic acids, and

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

• reaction pathways, selectivity, and catalytic efficiency. By exploiting dynamic acid–base equilibria or stimuli-responsive systems, chemists can manipulate substrate activation, stabilize reactive intermediates, and orchestrate complex multistep transformations under mild conditions [47]. In 2016, Lu's

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

• strategies for cyclobutyl scaffolds [53][54][55], products 6 and 7 could be synthesized via mild conditions [68]. Inspired by recent advances by Nolan and co-workers demonstrating the synthetic power of gold catalysts in EnT catalysis [31][69][70][71][72], we probed the reactivity of [Au(SIPr)(Cbz)] in our

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• catalytic efficiency (up to 99% yield). Keywords: chitosan-supported CuI catalyst; cyclization reaction; mild conditions; quinazolinone; Introduction Quinazolinones are not only a key core of nitrogen-containing benzo heterocyclic compounds found in many natural products and bioactive molecules [1][2][3

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

• by the regio- and stereoselective allylation with p-toluenesulfonyl cyanide. The proposed methodology is efficient for accessing acyclic β,γ-unsaturated nitriles with α-all-carbon quaternary centers and achieves yields up to 99% and excellent regio- and E-selectivity. The reaction proceeds under mild

• conditions and shows broad applicability to di- and trisubstituted allenes. Its practicality is demonstrated through the gram-scale synthesis and functional group transformations of amines, amides, and lactams, emphasizing its versatility and synthetic significance. Keywords: α-quaternary nitrile; Cu