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

• contraction of six-membered cycles in the synthesis of functionalized cyclopentane/enones, which are biologically active compounds. The main synthetic methods of ring contraction (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• traces of the desired product. Methods for the installation of a CF3-group on enones are limited, although approaches have been applied to quinones, uracils, flavones or arylenones via radical pathways [39][40][41][42]. As per the fluorination reactions, we envisaged that a leaving group in the β

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

• . Melchiorre and co-workers reported a dual catalytic system that involves photoredox and chiral organocatalysts for the construction of all-carbon quaternary centers. The authors studied radical additions to β,β-disubstituted cyclic enones (Scheme 7) [29]. The dual catalytic system of tetrabutylammonium

• decatungstate (TBADT) and chiral amine 33 was able to catalyze the reaction between benzodioxoles 32 and cyclic β,β-disubstituted enones 31. Cyclic ketones 34 bearing all-carbon quaternary stereocenters at the β-position were obtained in good yields and high enantioselectivity. Enzyme-catalyzed radical

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

• intermediate furan-derived enones. Subsequent reductive amination was performed in the presence of ammonia or amines and Pd/Al2O3 under H2 pressure, providing the tetrahydrofuran-derived amines [184]. The same catalytic system could allow the one-pot preparation of tetrahydrofuran-derived secondary and

• trans-4,5-diamino-cyclopent-2-enones and 2,4-diaminocyclopent-2-enones [186]. In 2021, Coelho and Afonso prepared a silica-supported copper catalyst (Cu/SiO2-N2) by impregnation with copper nitrate, and used it for the reaction of furfural with secondary amines (alkyl, cyclic and aromatic) to produce

• trans-4,5-diaminocyclopent-2-enones in hexane/isopropanol solvent mixture under continuous flow conditions (Scheme 56). The scope could be extended to 2-substituted trans-4,5-diaminocyclopent-2-enones by using 3-substituted furfurals [187]. A copper triflate-based analogous strategy was also reported

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• 11 in the presence of AcOH by exposure to UV-light at 254 nm occurred exclusively to provide an inseparable mixture of 32 and 33 (Table 1, entry 5). Subsequent dehydration of the resultant mixture with SOCl2 and pyridine yielded separable enones 34 (51%) and 10 (9%) over two steps. The structure of

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

• scaffold (Figure 1A, bottom), with increasing excited state energy moving from stilbenes and conjugated dienes to simple dienes, styrenes and enones (not shown) [28]. Consequently, small truncated chromophores, such as simple alkenes remain an intractable challenge for efficient EnT due to prohibitively

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• ]. Kowalczyk and co-workers showed how asymmetric organocatalysis can benefit from mechanochemical activation. They established that Michael additions of thiomalonates to enones, catalyzed by cinchona-derived primary amines, is efficient and enantioselective under ball-milling conditions [24]. Kondratyev and

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

• -naphthol by applying a new ligand L14, leading to the rapid construction of differently substituted chiral spirocyclic enones 40a–j with high yields and enantioselectivities (Scheme 41). It is worth noting that when the C4 position of 1-naphthol was occupied, the reaction occurred at the C2 position

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• significant advancement in mechanocatalysis. The stereoselective addition of bisthiomalonates 1–4 to cyclic enones and 4-chlorobenzylideneacetone proceeds stereoselectively under iminium activation conditions secured by chiral primary amines, in contrast to oxo-esters as observed in dibenzyl malonate addition

• nitroalkenes or guanidine-mediated addition of bisthiomalonates to maleimides, cyclic enones, and acyclic 1,4-dicarbonylbutenes, albeit at low temperatures and with relatively long reaction times, further limited to a narrow scope of thioesters (Scheme 1) [31]. Recently, we described a cinchona-squaramide

• -based catalytic system for the highly stereoselective addition of various bisthiomalonates to chalcones and dienones [29]. While recognizing the potential for greater selectivity enhancement and time savings with ball milling, hydrogen-bonding catalysis was effective only with aromatic enones, yielding

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• treatment of Alzheimer's disease [3][4]. Likewise, RL91 and BHMPC are active for selective cell growth inhibition of the resistant lines (Figure 1) [5][6]. Their synthesis mainly involves a cascade Michael–aldol reaction between enones and suitable Michael donors such as β-ketosulfones, β-diketones, or

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• aryl halides [42]. PEM reactors are also gaining industrial attention. Weber et al. reported a series of large-scale syntheses using PEM reactors [43]. We studied electrochemical transformations [44][45][46][47][48][49] and recently reported the selective reduction of enones using a PEM reactor [50

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• organocatalyzed asymmetric Michael addition reaction of 4-monosubstituted pyrazol-5-ones to simple enones for the synthesis of pyrazolone derivatives [25]. Despite these progresses, arylidene/heteroarylideneacetones have remained untapped by 4-unsubstituted pyrazolin-5-ones under asymmetric organocatalytic or

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• components, such as various acrylates, α,β-unsaturated acids, enones, enals, acrylamides, vinyl phosphonates, and vinyl sulfones. Various cesium salts of oxalates also performed well using this protocol. Isopropyl and tert-butyl groups present in an adjacent position of oxalates do not disturb the reaction

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• aromatic ring, to make the compound UV-active. Previously developed probes containing both MS and UV–vis tags have proven to be successful in cell supernatant in identifying a number of functional groups including epoxides, enones, citrulline, conjugated alkenes, and others [8][9][10][11][12][13][14][15

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• oxidation, whereas in Nicewicz's report, the alkene is oxidized. This modification allows for a significantly larger reaction scope (Scheme 29). Terminal alkenes and several functional groups such as ethers (163), esters (165), ketones (166), nitriles (167), and enones (170) are tolerated. The

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• Technical University, Institutsky per., 5, Saint Petersburg, 194021, Russia, SAMS Research Group, University of Strasbourg, Institut Charles Sadron, CNRS, 67200 Strasbourg, France 10.3762/bjoc.19.105 Abstract Trichloromethyl-substituted enones (1-aryl-4,4,4-trichlorobut-2-en-1-ones, ArCOCH=CHCCl3, CCl3

• -enones) undergo intramolecular transformation into 3-trichloromethylindan-1-ones (CCl3-indanones) in Brønsted superacid CF3SO3H (triflic acid, TfOH) at 80 °C within 2–10 h in yields up to 92%. Protonation of the carbonyl oxygen of the starting CCl3-enones by TfOH affords the key reactive intermediates

• -4,4,4-trichloro-3-hydroxybutan-1-ones; ArCOCH2CH(OH)CCl3) undergo dehydration to the corresponding CCl3-enones, which are further cyclized into CCl3-indanones. The yields of CCl3-indanones starting from CCl3-hydroxy ketones are up to 86% in TfOH at 80 °C within 3–18 h. Keywords: carbocations; enones

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• . Trialkylboranes can react in a similar way with enones [3] whereas, distinctively, suitable acceptors for the reaction with dialkylzinc reagents also include α,β-unsaturated carboxylic acid derivatives such as α,β-unsaturated (di)esters [4][5], N-enoyloxazolidinones [6][7], N-enoyloxazolidines [8], or

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• complex 57 was obtained through reduction of the phenoxyimine-imidazolium bromide 55a (R = t-Bu) with NaBH4 followed by successive alkylation with iPrBr and reaction with Cu2O (Scheme 19) [32]. The use of the synthesized complexes 56a and 57 as precatalysts for the 1,4-conjugate addition to enones and the

• [(IMes)2Cu]+FHF− (91) was also obtained. These complexes exhibit an interesting catalytic activity that will be described later. 2 Application as catalysts In 2001, Woodward, for the first time, reported an NHC–Cu-mediated catalysis in the conjugate addition of diethylzinc to enones (Scheme 33) [46

• arylaluminium reagents to five-, six-, and seven-membered β-substituted cyclic enones (Scheme 42). It is obvious that the NHC–Cu(I) complexes are generated in situ through transmetallation. For arylation reactions, Me2(Ar)Al reagents were used. The substrates having a variety of substituents (R = CH2Bn, n-Bu

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• example, when esters 1a are subjected to Lewis acid-induced denitration, highly electron-deficient enones (reaction b) [4] are obtained. The latter compounds are highly reactive and undergo reaction with, e.g., mercaptoacetaldehyde affording thiophenes (reaction c) [5] or with activated (hetero)aromatic

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• , imines, other Michael acceptors, or alkyl halides. Our group is developing trapping of metal enolates with stabilized carbocations and could show that magnesium enolates generated from enones [22], unsaturated amides [23], or heterocycles reacted with tropylium, dithiolylium or flavylium cations [24

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• ]oxaphosphepin-5(4H)-one 2-oxides from 2-phenyl/alkoxy-4H-benzo[d][1,3,2]dioxaphosphinin-4-ones and dialkyl 2-benzylidenemalonates. Synthesis of bicyclic seven- and eight-membered phosphotones from cycloalk-2-enones and dimethyl phosphonate. Synthesis of binaphthylene-fused phosphotones from (M)-2'-methyl-[1,1

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• enolate. González-Gómez et al. studied the tandem conjugate addition of dialkylzincs to cyclic enones (9, 12) and the subsequent reaction of the enolate with N-tert-butanesulfinylimines 10 (Scheme 4) [24][25][26]. Their method was applied to a broad range of substrates (5–7-membered rings) with equally

• using acyclic enones 14 [27]. Their tandem conjugate addition/Mannich reaction methodology offers access to various non-cyclic β-aminoketones 16 with multiple contiguous stereocenters in high diastereo- and enantioselectivity (Scheme 5a). Additionally, chiral isoindolinones 18 and 2,3,4-trisubstituted

• imines or their synthetic equivalents. Furthermore, we wanted to develop an enantioselective and diastereoselective process without adding chirality elements within the reagents. For our initial studies, we have selected the well-studied cyclic enones as substrates and the Taniaphos ligand (L14) that has

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• -indoline and gave the Bpin-N-indoline product 27; this was suggested as the major pathway (Scheme 7). Thomas et al. reported the H-B-9-BBN-catalysed reductive cyanation of enones with HBpin and N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) (Scheme 8) [71]. The reaction was proposed to proceed by 1,4

• fluoride 50 to give the ester 51 and FBpin (Scheme 11). The H-B-9-BBN-catalysed 1,4-hydroboration of enones with HBpin was shown by Thomas, including the subsequent functionalisation of the intermediate Bpin-enolate 52 (Scheme 12) [76]. The proposed mechanism began by 1,4-hydroboration of the enone 29 with

• reaction of enones and esters or lactones (Scheme 14) [77]. Through a series of single-turnover reactions, a mechanism was proposed (Scheme 14): H-B-9-BBN underwent 1,4-hydroboration with the enone 29, followed by B‒O/B‒H transborylation with HBpin to give an O-Bpin enolate 52 and regenerate H-B-9-BBN

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

• ethers 12 [19] and metal-catalyzed cross coupling of alkenes 13 and enones 14 [20][21] have been reported. However, these reactions face multiple disadvantages such as limited substrate scope, use of hazardous solvents and harsh reaction conditions such as high temperatures or acidic/basic conditions

• could be converted to enones 20 by hydrozirconation followed by Pd-catalyzed acylation with acyl chlorides 21 [61]. The substrate scope required aryl units at either alkyne or acid chloride unit. Recently, we could extend this method to alkyl-substituted alkynes 16 and acetyl chloride (22), providing