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

• existing metal-catalyzed C–H bond functionalization methods (Scheme 3) [53]. Recently, Scheidt et al. discovered an NHC/organic photoredox-catalyzed three-component coupling reaction for the efficient and novel preparation of γ-aryloxy ketone scaffolds 12. This transformation builds on the emerging field

• is the reduction of acylazolium C to generate a stable benzylic radical D is formed, and this extends the lifetime of the radical, allowing for radical–radical coupling reaction to afford the desired γ-aryloxy ketones 12 in good yields. The utility of this sustainable method was further demonstrated

• amide via dual catalysis. Visible-light promoted cooperative NHC/photoredox catalyzed ring-opening of aryl cyclopropanes. NHC-catalyzed benzylic C–H acylation by dual catalysis. NHC/photoredox-catalyzed three-component coupling reaction for the preparation of γ-aryloxy ketones. NHC-catalyzed silyl

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• substructure hidden inside the natural product’s cage-like ring system, Kalesse’s group chose to construct this architecture first using a tandem Nazarov/ene cyclization [36]. The cis-pentalene was subsequently assembled via a Ti(III)-mediated epoxide–ketone coupling reaction. Starting from the known

• triflate formation followed by a palladium-catalyzed coupling reaction with AlMe3. The carbonyl group at C8, required for the subsequent aldol reaction, was introduced by enolate oxidation followed by Jones oxidation. Hydrolysis of the ketal at C11 afforded ketoester 64. A TBD (1,5,7-triazabicyclo[4.4.0

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• incomplete conversion resulted in Boc protected beta-alanine that was challenging to separate from the desired product (3). Carboxylic acid 3 then underwent a peptide coupling reaction with allyl-protected PNA backbone 4 to afford nitrobenzene 5 in 69% yield. Nitrobenzene 5 was then reduced to the

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• ]. Next, we performed the oxidative coupling reaction of 1 and W4 in CH2Cl2 catalyzed by anhydrous FeCl3 to give W1 in 35% yield [45]. For the synthesis of W2, we first oxidized triphenylene with CrO3 and 18-crown-6 to give triphenylene-1,4-dione (2) according to Echavarren’s protocol [46]. Triphenylene

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

• and NiCl2·diglyme, was used as the catalyst to obtain the coupling products 20 in good yield and high enantioselectivity. The first nickel-catalyzed asymmetric reductive cross-coupling reaction between acid chlorides 21 and secondary benzylic chlorides 22 was reported by Reisman and co-workers (Scheme

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• and co-workers developed a Chan–Evans–Lam-type oxidative cross-coupling reaction between N-arylphthalic hydrazides and arylboronic acids using copper catalysis [41]. Similarly, in 2003, Lee and co-workers introduced a desymmetrization approach employing simpler N=N precursors, specifically N-protected

• proposed. In the first step a C–N-coupling reaction with phenylhydrazine occurs [57]. The catalytic cycle starts by the formation of Pd(0) in situ through reduction facilitated by phosphine and water [58]. This is followed by the oxidative addition of aryl bromides, leading to the formation of the Pd(II

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• clarity. The relationship between the ACD values and excess of P conformer. Excess of P conformer (%) = ([P] − [M])/([P] + [M]) × 100, where [P] and [M] are the amounts of P and M conformers calculated by B3LYP/6-31G*, respectively. Coupling reaction of 1 and chiral primary and secondary amines. The

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

• production of jet fuel precursors through the electrocatalytic highly selective coupling reaction of furfural and levulinic acid. The Ni2+ species serves as the active site for the coupling process (Scheme 53) [181]. A similar strategy involving phenolic compounds and furfural allowed the production of

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

• and transformations of 43 produced hydroxyketone 44. Due to the steric hindrance of this substrate, the subsequent Suzuki cross coupling reaction with 3-boronophenol proceeded in low yield. To address this issue, Han′s group employed a novel palladacycle catalyst 45, previously developed by their

• -catalyzed Suzuki cross-coupling reaction of sterically hindered substrates developed by Han [35][36][37], the coupled product 57 was obtained in a satisfactory yield (72%) from 55 and pinacol boronate 56, along with trace amounts of the double bond migrated side product 58 (57:58 = ca. 15:1). Demethylation

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• –B [14] (Scheme 3E) bonds. In the case of an asymmetric cross-coupling reaction (Scheme 3C) [10], both sets of the substituents on individual aryl groups are considered because neither is involved in the bond formation/cleavage. Accordingly, the catalyst-controlled atroposelective Suzuki–Miyaura

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

• recently proposed by Marzo and co-workers in an NHC-mediated coupling reaction with alkyl halides mediated by (TMS)3SiH [55]. The O-silylated product 5 could result from a subsequent radical C-silylation followed by a Brook-type rearrangement process [56]. Interestingly, performing the TESH-mediated

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• through circular dichroism (CD) and circularly polarized luminescence (CPL) spectroscopy. Results and Discussion The syntheses of N-doped macrocycles MC1–3 are shown in Scheme 1. Diamines 1a and 1b were synthesized by double Pd-catalyzed C–N coupling reaction of 4,6-dichlorobenzene-1,3-diamine with phenyl

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• -pinacol coupling reaction are efficient, they often require more than stoichiometric amounts of metal reductants and produce significant quantities of metal waste, which in some cases can present considerable environmental and safety concerns. To mitigate this issue, more sustainable approaches, such as

• resulted in a wide range of diamines, obtained in moderate to good yields. Inspired by these works, we aimed to investigate and optimize the stereoselective electrochemical intramolecular imino-pinacol coupling reaction under both batch and continuous flow conditions as a direct approach to enantiopure

• vicinal diamines. Historical perspective on electrochemical imino-coupling protocols. Stereoselective electroreductive intramolecular imino-pinacol reaction. Scope of the imino-pinacol coupling reaction. Reaction conditions: GC electrodes, NEt4BF4 (2.6 equiv), MsOH (3 equiv), constant current 5 mA (2.5 mA

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

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• [20], or, more recently, (iii) prepared via an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction (Scheme 1A) [18]. The reported synthetic route relies on an initial 4-step preparation of the isonitrile precursor, which was accomplished in an overall yield of ca. 14%. The

• . 20% (4 steps) relative to an overall yield of ca. 5% via the preparation of the isonitrile followed by the Fe hydride initiated isonitrile–olefin intramolecular coupling reaction [18]. Protection of the indole nitrogens with the Boc group was preferable to the use of benzyl protecting groups since

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

• : 4-methoxyacetophenone (MAP) and 2,2-dimethoxy-2-phenylacetophenone (DPAP), in a frozen state (−80 °C) with acetic acid as the solvent. A second thiol–ene coupling reaction between the 1,2-cis-glycosyl thiols and the 2-substituted glycals produced a series of α,α-1,1'-thiodisaccharides with high

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• high enantioselectivities. Beyond planar and axial chirality, the same group developed a three-component coupling reaction of 2,2′-diisocyano-1,1′-biphenyls 16, aryl iodides, and carboxylates (Scheme 3a) [30]. Under chiral palladium catalysis, unique inherently chiral saddle-shaped bridged biaryls 17

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

• the 6/5/5 skeleton, and a Heck coupling reaction constructing the [3.2.1] framework, are the two key reactions in this 11-step synthesis. Keywords: [3 + 2 + 1] cycloaddition; selective estrogen receptor modulators; synthesis; tetrahydrofluorenone; Introduction Estrogen receptors (ERs) [1][2] are

• alkyne moiety is installed via Sonogashira coupling reaction using aryl iodide 5. The cyclopropyl ring in 5 can be introduced via an SN2 reaction of compound 2 with tert-butyl cyclopropanecarboxylate (3). Scheme 5 summarizes the final successful execution of this route. The starting material 2 is a known

• % yield with a cyclopropyl group. Then reducing the carboxylate group in 4 with DIBAL-H afforded alcohol 5 in 67% yield. Next, Sonogashira coupling reaction between 5 and trimethylsilylacetylene generated 6 with an alkyne moiety quantitatively. After that, the hydroxy group in 6 was oxidized into a

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• hybrid decamer 3 in a previous report [26], via a Suzuki–Miyaura cross-coupling reaction between dibromo precursor 1 and borylated precursor 2 (Scheme 1). The resulting mixture was successfully separated by column chromatography on silica using CH2Cl2/n-hexane as an eluent to give icosamer 4 in 6% yield

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

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• exceptionally high yield (97%). A Suzuki cross-coupling reaction between 47 and 45 gave compound 48 which was subjected to a final Scholl oxidation using DDQ. The target compound 49, containing two azulene subunits, was obtained in a relatively low yield (16%). Analysis of NICS values for 49 revealed similar

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• these sulfones with epoxides 23b and 23a, respectively. Following the literature procedure for a similar reaction, using n-butyllithium in the presence of BF3·Et2O at −78 °C, the coupling reaction unfortunately resulted in the decomposition of the reactants (Scheme 4). The authors hypothesized that the

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• yield of 88%. (R)-Methyl 6-oxopipecolate (7) was converted under Vilsmeier–Haack conditions [35][40][41] to undergo N-formylation and concomitant enol bromination to give product 2 (Scheme 2). Due to slow degradation of the bromide 2, the subsequent cross-coupling reaction was conducted immediately

• reduction product 13 of a Sonogashira–Hagihara cross-coupling reaction. This was synthesised under similar conditions as the Suzuki–Miyaura counterpart 3 utilising the same Pd catalyst, base and solvent. In addition, 10 mol % CuI as a co-catalyst and 2.0 equiv phenylacetylene (12) were used, resulting in

• –Miyaura cross-coupling reaction between bromide 2 and a variety of boronic acids 8. Reaction of 3a to (2R,6S)-9a and (2R,6R)-9a. The chromatograms prove the simple diastereoselection. a) Sonogashira–Hagihara cross-coupling reaction followed by b) NaBH3CN reduction of the N-acyliminium species and c

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

• multimetal-organic framework (M-MOF, M= Cu, Ni) which successfully catalyzed the one-pot cyclopropenone hydration/Chan–Lam coupling reaction of 309 and boronic acid 341 to give the corresponding ester 310 in good yield via the formation of acid 342 (Scheme 76B). Cyclopropenone was also subjected to non-metal

• ) [131]. In addition, a gram scale operation has been successfully demonstrated. In addition, Hu and co-workers (2020) studied a catalyst-free multicomponent coupling reaction of benzynes derived from alkyne 349, cyclopropenone 309, and sulfoxides to give the corresponding o-(methylthio)phenyl acrylates

• and using ylide 397 altered the stereoselectivity to E-isomeric products 400 and 401 [144]. Wu and co-workers (2020) employed Pd to mediate the cross-coupling reaction of sulfoxonium ylide 402 and benzyl bromides to give the corresponding (Z)-ethyl cinnamates 403–406 in good yields via carbene

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• pyrrolopyrimidine derivatives. The envisioned methodology combines a Sonogashira–Hagihara reaction and a one-pot process comprising a Buchwald–Hartwig coupling reaction followed by a hydroamination [23][24]. Results and Discussion The bromination of 6-chloro-1,3-dimethyluracil (1) afforded, following a known

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80