α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• sufficiently electrophilic carbonyl carbon atom with the elimination of triphenylphosphine oxide via the aza-Wittig reaction. It should be noted that the best method for the isolation of quinoxalinones 9 was column chromatography using an elution gradient of hexane/ethyl acetate 3:1 to hexane/ethyl acetate 1:2

• shift of the signal in the 198 ppm region, corresponding to the carbonyl carbon of compounds 8, to a stronger field in quinoxalinones 9, where cyclization of the keto group has occurred. The structure of quinoxalinones of type 9 was finally assigned based on X-ray diffraction analysis made for 3-(4-(2

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

• transformations of carbonyl substrates with umpolung processes of aldehydes such as the benzoin condensation and Stetter reaction being particularly well studied [4][5][6][7][8][9][10][11]. In these processes, addition of the NHC to the aldehyde followed by proton transfer generates the enamine-like Breslow

• intermediate A (Figure 1a), in which the formerly electrophilic carbonyl carbon reacts as a nucleophilic center. In this way, the traditional reactivity profile of the carbonyl group is transiently inverted, and unconventional product classes are generated. Alternatively, addition/elimination of the NHC to a

• species C benefitting from additional stabilization by virtue of electron delocalization onto the NHC-derived azolium ring [17][18][19][20]. Similarly, the cationic azolium fragment in acylazolium salts can effectively lower the carbonyl reduction potential relative to the starting material with single

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• intermediate 22 (see Supporting Information File 1 for the details). Reasoning that the preferential coordination of the palladium catalyst with the hydroxy group at C15 and the carbonyl group at C18 in compound 22 may have deactivated the palladium catalyst [34], we protected the hydroxy group. Compound 22

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• stereoisomer has the ring-junction NC–H bond, the imide carbonyls, and the oxindole carbonyl all cis to one another across the two newly formed rings. This must arise from a preference for an exo transition state that places the incoming maleimide away from the oxindole carbonyl. The cascade chemistry allows

• same stereochemical outcome predominates. There are two possible exo transition states, both of which avoid steric (and electronic clash) of the dipolarophile carbonyls with the oxindole. Of these, the preference appears to be for the dipolarophile carbonyl groups, in this case for dimethyl maleate, to

• approach the nitrone on the side opposite the oxindole carbonyl (in a similar way to that shown in Figure 2 for the maleimide). Conclusion In conclusion, we have demonstrated the feasibility of our approach to the core of several Alstonia alkaloids by using a cascade cyclisation–dipolar cycloaddition

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• of carbonyl compounds, such as aldehydes or ketones, with active methylene compounds [37]. The resulting α,β-unsaturated carbonyl products can then be further elaborated to form natural products, therapeutic agents, polymers, pesticides, and insecticides [38], which have important applications in the

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

•  14, box) and repulsion between the aryl and the carbonyl group in the E-isomer. Some studies on N-acylindigo derivatives reported, besides the expected spectral blue-shift, also a decrease in the fatigue resistance due to photochemical rearrangements [68][69]. Dube and co-workers reported a series of

• interesting results: in the case of derivative 63 containing pyrrole, capable of hydrogen bonding with the carbonyl oxygen (Scheme 20, left) [61][62], the E form is obtained almost quantitatively upon irradiation. In the case of pyridine-containing derivative 64 (Scheme 20, right) no photoswitching is

• pronounced red-shift of the E-isomer was observed for the pyrrole derivative 66 [81], showing that the hydrogen bond between pyrrole and carbonyl also plays a role (Scheme 21, left). The band separation also provides almost quantitative PSS in both directions. The imidazole derivative 67 (Scheme 21, right

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

• promising industrial relevance. Oxidative cleavage of alkenes to yield carbonyl compounds is one of the key transformations in synthetic organic chemistry [41][42]. Over the past two decades, this field has witnessed significant advancements, primarily through the use of organic oxidants and transition

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• through a σ-type intermolecular halogen bonding (C–Br···O) between the ortho-bromine atom and the carbonyl oxygen. The formation of similar heterochiral polymers through a σ-type intermolecular halogen bond (C–Br···S) was also found in crystals of the thio-analogue rac-II. On the other hand, in the

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• between the H4-H5, H5-H6, H6-H7, and H1-H2 protons, as well as long-range coupling between the H2-H8 protons. Again, these data are fully consistent with those published previously [20]. Together, these results indicate the presence of two indoles, one carbonyl, one methylene, and one methine group where

• the connectivities of these groups were supported from the 1H-13C HMBC spectrum. Couplings between the H8 and C9 (or H8′ and C9) atoms are consistent with the C8 and C8′ atoms linked to the carbonyl carbon (C9). In addition, couplings between the H8 and the C2, C3, C3a, and C8 carbon atoms, as well as

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• issue is a fundamentally important factor. In the present work, the reactivity of the hypophosphites of alkali metals (Li, K, Rb, and Cs) in reductive amination was explored for the first time. A set of secondary and tertiary amines was synthesized from various types of carbonyl compounds and amines

• has shown clear influence of the cation in the hypophosphite salt on the effectiveness of the reductive amination. The acidity of the reaction media was a key factor affecting the equilibrium in the interaction between carbonyl compounds and amines. Intermediately acidic media is the optimal for the

• substrate scope of the developed synthetic approach was investigated. Aromatic and aliphatic carbonyl compounds reacted with primary and secondary amines. The reductive amination efficiently proceeded with both cyclic and acyclic secondary amines. Steric hindrance in ortho-position in carbonyl compound 13

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• carbonyl group, giving 7 in 59% yield. Then, under basic conditions, the aldehyde group in 7 was converted into a vinyl group via Wittig reaction, affording yne-VCP substrate 8 in 90% yield. During this process, the TMS protecting group was lost. We then investigated the [3 + 2 + 1] reaction of 8 and CO

• )2Cl]2 catalyst can be reduced to 3.6 mol % (the reaction scale was 20.6 mmol). After finishing the key [3 + 2 + 1] reaction, we focused on building the D ring in 1. Initially, we tried to directly close the ring through addition of the α position of the carbonyl group to the bridgehead vinyl group

• introduce an ester group at the α position of the carbonyl group in 9 to get compound 10, which could have a more nucleophilic carbon better for the Heck reaction. 10 was obtained in 70% yield with a diastereomeric ratio of 4.5:1. Then, we screened various palladium catalysts and solvents to accomplish the

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• used in the synthesis of a good number of target molecules, including complex natural products [32][33][34][35]. Typically, the LA binds the dienophile through a donor–acceptor interaction (usually involving a carbonyl group) which results in a significant stabilization of the dienophile’s LUMO. As a

• following subchapter) but also to other processes such as aza-Michael additions or processes catalyzed by species able to establish noncovalent interactions with the reactants [52][53][54][55][56][57]. Lewis acid-catalyzed carbonyl–ene reactions Similar to the Diels–Alder cycloaddition reaction, the Alder

• , typically binds a carbonyl group in the enophile partner. In this sense, the acceleration is even more significant in the so-called carbonyl–ene reaction [63], an analogous process where a carbonyl group directly acts as the enophile. This transformation has also been applied to the synthesis of complex

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• formal substitution of the carbonyl oxygen atom of DiBA to an NH group, could act as a pH-responsive molecular switch (Figure 1c). Namely, the double-bond nature of an amidine moiety can be altered by the protonation of the amidine nitrogen atom. This suggests the possibility of controlling the rate of C

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• known that nitrile oxides are capable of reacting with various multiple carbon–heteroatom bonds [28]. In contrast to the products of nitrile oxide cycloaddition to imino groups, 1,4,2-oxathiazoles, formed by addition to C=S bonds, are unstable and undergo decomposition into isothiocyanate and a carbonyl

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

• successfully introduced into homogeneous [26][27][28][29] and heterogeneous [30][31] carbon–carbon and carbon–heteroatom bond-forming protocols. Although its reactive carbonyl group could limit its application when a strong base (aldol condensation [29]) or amines (potential Schiff-base formation) are present

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; nickel; photocatalysis; Introduction Enaminones are relevant intermediates in organic chemistry and the pharmaceutical industry [1][2][3][4][5][6]. These enamines have a carbonyl group conjugated to a carbon–carbon double bond, owing its great versatility in organic synthesis to its ability to

• adduct 10 was identified using GC–MS (Figure S1, Supporting Information File 1). When the reaction was performed under air-equilibrated conditions, the intended product 9a was obtained in a 31% yield, indicating that air influenced the interaction between the Ni-catalyst and the α,β-unsaturated carbonyl

• , pseudo-octahedral Ni(II) complex [44] involving the carbonyl groups of PS1 and 7a, which is further activated on aggregation of the pyridinium salt and the chromone aromatic ring through π−π stacking. Then, PC1 was submitted to Stern–Volmer quenching experiments. Whereas no interaction occurred between

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• well-ordered large domains on graphite and are revealed by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) studies. The molecular level arrangement in the assembly reveals a hexagonal packing through weak non-bonding interactions between the carbonyl and aromatic hydrogen, and is

• is to be noted that the fluorine atoms are oriented toward the aromatic and aliphatic hydrogen and the carbonyl group to aromatic hydrogen. This suggests possible directional non-bonding interactions between the molecules. For molecules with 3-fold symmetry, the 3-fold orientation within the assembly

• the vectors. Black arrows indicate the compact lattice directions of graphite. Magenta dashed lines depict possible non-bonding interactions between carbonyl groups and aromatic hydrogen atoms. Blue dashed lines depict the same between fluorine and aromatic/methyl hydrogen atoms. (a) Current versus

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• Cyclobisbiphenylenecarbonyl (CBBC) represents a readily available chiral figure-eight macrocycle containing two carbonyl groups. However, the transformation of the carbonyl groups has been unexplored. Herein, we conducted the Wittig reaction of CBBC with methylenetriphenylphosphorane to furnish two chiral macrocycles

• containing one or two exocyclic olefin units. Owing to the transformation of carbonyl groups, the resulting products exhibit several unique physical and chemical properties: (1) the enhancement of configurational stability, (2) the appearance of fluorescence, and (3) the reductive carbon–carbon-bond

• formation between carbonyl and alkene units. Keywords: bathtub; chirality; cyclobisbiphenylenecarbonyl; figure-eight; Wittig reaction; Introduction Figure-eight π-conjugated molecules represent chiral macrocycles with a twisted crossover structure [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• carbonyl-nitrogen embedded hetero[7]helicenes 25a and 25b bearing axial chirality [39]. Compound 25a displays excellent optical characteristics with ΦF = 0.57, |gabs| = 1.7 × 10−2, |glum| = 1.4 × 10−3, and a BCPL of 8.94 M−1 cm−1. Then, Chen’s group contributed triple aza[6]helicenes 26a and 26b with |glum

• and co-workers introduced an intramolecular radical cyclization strategy to synthesize highly luminescent tetraceno[6]helicenone and its aza analogue 76 [90] (Table 26). The incorporation of a carbonyl group into the helicene backbone substantially enhanced fluorescence quantum yields and red-shifted

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• , pyridinyl, furyl, isopropyl, and cyclohexyl substituents were introduced into position 3; cyano and various carbonyl groups were added to position 4 and cyclic amine residues were added to position 5 which increase the solubility of the synthesized compounds 3 (Scheme 2). An analysis of the yields of

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• (δH 1.10, d, J = 6.9 Hz) revealed the presence of a threonine moiety in 1. Strong HMBC correlations from H-5, H-8 and H-9 to the carbonyl carbon C-7 (δC 167.2) confirmed an amide bond by which the salicylic acid and threonine residues were linked. The deshielded carbon signal at δC 172.9 was assigned

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

• stable isosteric replacements for gem-dimethyl and carbonyl groups. This work reviews possible synthetic strategies towards these strained heterocycles, covering both de novo constructions of the 4-membered ring as well as derivatisations of oxetane building blocks, then reactivity of oxetanes in terms

• base [5]. In fact, its hydrogen-bond-accepting ability is even stronger than that of the other 3-, 5- and 6-membered cyclic ethers, as well as the carbonyls of aldehydes, ketones, esters and carbonates [6][7][8]. The only better carbonyl-based hydrogen-bond acceptors are amides, carbamates and ureas [9

• ]. The first to recognise that these unique physicochemical properties may have valuable applications in medicinal chemistry were Carreira, Rogers-Evans, Müller and colleagues, who together reported that 3-substituted oxetanes can serve as isosteric replacements for carbonyl and gem-dimethyl groups

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

• -/trifluoroalkylation reagents, α-carbonyl alkyl bromides/alcohols, alkyl halides, and alkyl carboxylic acids, have been successfully applied to this transformation to afford 3-substituted indolin-2-ones. In 2013, Li’s group reported a novel DTBP(di-tert-butyl peroxide)-mediated oxidative 1,2-alkylarylation of

• to the formation of radical annulation species 59. Single-electron oxidation and deprotonation then take place, resulting in the final cyclized products 56a. N-Arylalkenes: α-carbonyl alkyl C(sp3)-centered radicals In 2014, Li’s group developed an oxidative difunctionalization of N-arylacrylamides

• selectivity, and high functional group compatibility (65a–f). In 2024, Huang, Liu, and Li’s group introduced a novel approach for the photochemical radical cascade 6-endo cyclization of dienes using α-carbonyl bromides, as illustrated in Scheme 32 [20]. This method is characterized by a visible-light-induced

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• precursors of α-substituted carbonyl compounds that have been recently applied as coupling partners for radical functionalization with the formation of C–C [63][64][65][66] and C–Het [67][68][69][70] bonds. The ready availability of enol acetates from the corresponding carbonyl compounds in just one

• reactions leading to the corresponding unfunctionalized carbonyl compounds. To date, only the Xu group reported oxidative phosphorylation of enol acetates with dialkyl H-phosphonates and Mn(acac)3 as an oxidant (Scheme 1b) [71]. However, the reported approach is limited by an excess of manganese salt, long

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• resulted in more specific SMARTS patterns matching the DG. For example, Figure 3a shows the result from Tomberg et al. [9], which does not include the carbonyl oxygen in the SMARTS pattern match although the pattern marked in red in Figure 3b is part of the database. This example also highlights that in