Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• linker provides entry to 1,2,3,6-tetrahydropyridines. Additionally, in the absence of internal nucleophiles, this methodology yields aryl-substituted 1,3-dienes. This work introduces a palladium-free, single-step alternative to multistep heterocycle construction from propargylsilanes and highlights the

• propargylsilane 7d halogenation–cyclization cascade and Suzuki–Miyaura cross-coupling in the second step [22]. Thus, we have developed a faster and palladium-free route towards tetrahydrofurans 8. The latter can still be modified further through silicon–halide exchange followed by cross-coupling chemistry as

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

• (±)-4 from pentacyclic starting materials 5 and 6, respectively (Scheme 1B). In 2021, Dai reported the total synthesis of (±)-4 from cyclopentanol 7, in which the bicyclic spiroketal moiety and (Z)-3-butenoate side chain were formed via a palladium-catalyzed carbonylative spirolactonization and Z

• were developed. A straightforward transformation was designed involving a cross-metathesis of the C13–C14 double bond and a palladium-catalyzed decarboxylative allylation [32] as the key steps. With 14 in hand, we investigated the feasibility of cross-metathesis of the C13–C14 double bond. Initially

• of 21 with allyl alcohol and triphenylphosphine afforded transesterification product 22 in 21% yield [33], accompanied by unidentified decarboxylation by-products. A variety of standard conditions failed to promote the palladium-catalyzed decarboxylative allylation of allylic β-ketocarboxylate

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

• Road, Hong Kong, China Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, China 10.3762/bjoc.21.149 Abstract A series of nitrogen (N)-doped macrocycles was successfully synthesized through palladium-catalyzed arylation. X-ray crystallographic characterization

• palladium (Pd)-catalyzed arylation of aza[14]metacyclophane derivatives. By modulating the substitutions on the N atoms, two isomeric macrocycles, a C1-symmetric one as the minor fraction (MC1) and a C2v-symmetric one as the major product (MC2), were successfully obtained when 4-tert-butylphenyl groups were

• demonstrated the synthesis and characterizations of N-doped macrocycles MC1–3 by palladium-catalyzed arylations. The molecular structures of the macrocyclic precursors and targets were unambiguously revealed by X-ray crystallographic characterization. These macrocycles exhibit strong fluorescence with ΦF

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

• aldehyde and, if required, N-functionalisation via nucleophilic substitution (for aliphatic substituents) or palladium-catalysed cross-coupling (for aromatic substituents) (Scheme 25) [77]. Hemithioindigo can be synthesised by treating phenylthioacetic acid (83) with triflic acid. Then, the product is

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

• reaction type and the chirality type of resulting products. Perspective Isocyanide-based transformations Palladium-catalyzed isocyanide insertion reactions In 2018, Luo, Zhu, and co-workers developed a palladium-catalyzed enantioselective reaction between ferrocene-derived vinyl isocyanides 1 and aryl

• ) and aryl iodide 6a as the reactants, diastereomeric products 9a and 9b, each containing two distinct stereogenic axes (C–C and C–N), were obtained in 93% and 89% ee, respectively. Very recently, Luo and co-workers implemented an efficient palladium-catalyzed atroposelective C(sp2)–H imidoylative

• 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

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• thematic issue that visible light increases the reaction rate of palladium-catalyzed Negishi cross-couplings [34]. The integration of enabling technologies has also contributed to the success of photocatalytic organic synthesis [35]. Automated reaction platforms, high-throughput experimentation techniques

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

• 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

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• moieties, minimizing ground-state electronic interactions. In particular, the introduction of TPA groups aimed to enhance the electron-donating ability of the donor unit, while a phenyl spacer was introduced to modulate the distance between the donor and acceptor. The synthetic routes involved palladium

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

• synthesis of π-extended azulene was the non-benzenoid isomer of pyrene published by Ward and co-workers (Scheme 1) [31]. Cyclohept[bc]acenaphthylene (2) was obtained from a partially saturated precursor 1 via dehydrogenation using palladium on carbon. However, the reaction carried out at 300 °C gave 2 as a

• easily adapted to more modular approaches, limiting the variety of possible substitution patterns. This is why more modern approaches continue to be developed. Modern approaches to azulene-embedded nanographenes Modern synthetic approaches have greatly benefited from the discovery of palladium-catalysed

• dimerization of alkynes, followed by the expansion of a phenyl ring leading to the formation of an azulene moiety, was first reported over half a century ago. These reactions can be carried out using various catalytic systems, including sulfenyl chloride/AlCl3 [50], palladium catalysts [51] or gold catalysts

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

• selection, solvents, and current density, the best results were obtained using tetrabutylammonium bromide as the catalyst in CH₃CN, with a low catalyst loading of 2 mol %, and palladium wire as the cathode, yielding the target compound in 81% yield. This study capitalized on the use of bromide ions as redox

• with α-carbonylalkyl bromides using palladium (Scheme 29) [17]. This reaction was initiated by a Heck insertion and required Ag2CO3 as an oxidant. It proceeded via a tandem C–Br/C–H functionalization and cyclization steps, ultimately realizing an oxidative radical pathway. The process exhibited a broad

• . Control experiments confirmed the necessity of both AIBN and DTBP, with higher temperatures favoring the desired cyclization over side reactions. In 2021, a novel excited-state palladium-catalyzed alkylation/annulation reaction was developed to achieve reaction of unactivated alkyl chlorides, facilitating

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

• , thereby dictating the site of C–H activation. Common DGs include unsaturated heteroatoms and alkenyl groups, which have proven effective in guiding the regioselectivity of these reactions [4]. Mechanistic studies with palladium(II) acetate (Pd(OAc)2) as catalyst support the following mechanism of C–H

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• -OES, the precipitation ability of α-CD (0.2 mmol × 2) of a solution containing gold in the presence of palladium and platinum (33 mM KAuBr4, 33 mM K2PdBr4, and saturated K2PtBr4, at ≈26 mM), with 78.3% of the gold precipitating out of solution while for the other metals there was only precipitation of

• precious metals [42]. The process of gold precipitation with cyclodextrins, bromic acid and potassium hydroxide to form the potassium bromoaurate salt was patented, with patent coverage expanding to metals like silver, platinum, palladium, and rare earths, as well as the use of other cyclodextrins, β- and

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

• column chromatography. The vinyl bromide 2 had been shown to undergo palladium-catalysed cross-coupling reactions, e.g., Suzuki–Miyaura or Sonogashira–Hagihara cross-coupling reactions [35]. Emphasis was placed on the Suzuki–Miyaura reaction to give a variety of arylated compounds, as previous attempts

• , heterogeneous catalytic hydrogenation of the enamine with palladium on carbon was chosen. While the hydride reduction of the acyliminium intermediate gave a nearly 1:1 diastereomer ratio, a 9:1 ratio was obtained for the catalytic hydrogenation (Scheme 4). While the hydride reduction of the N-acyliminium

• species did not show any significant diastereofacial discrimination, the catalytic hydrogenation occurs stereospecifically, particularly in the case of hydrogenation with palladium on carbon [49][50][51][52]. In this case, we propose that the restraints exerted by the first stereocenter lead to 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

• -branched (L/B) selectivity of >20:1. The reaction involves the formation of palladium hydride (Pd–H) 270 as the key species followed by alkyne and CO insertion reactions via 271 and 272 (Scheme 68A) [116]. On the one hand, Jia and co-workers (2021) utilized environmentally benign water as the hydrogen

• CO insertion (295) and transmetalation with palladium hydride to afford the acylpalladium species 296 (Scheme 71B) [122]. Utilizing a non-precious transition metal as an alternative for Pd, Yoshikai and co-workers (2020) reported the cooperative cobalt/Lewis acidic AlMe3-catalyzed hydrocarboxylation

• bond of cyclopropenone to give a cyclic intermediate 316 (Scheme 74A) [125]. On the other hand, Wu and co-workers (2022) developed a Pd-catalyzed selective ring-opening of cyclopropenones and vinyl epoxide 318 to give the corresponding esters 319–321 in good yields via a π–allyl palladium intermediate

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• the resulting product (S)-13a in the presence of FeCl3 as the catalyst, the corresponding malononitrile derivative (S)-16 was obtained without any loss in optical purity. Keywords: asymmetric allylic amination; axial chirality; isatin; palladium catalysis; P,olefin-type chiral ligand; Introduction

• palladium catalysts with amines as nucleophiles have been reported [14][15][16][17][18][19][20][21][22][23][24][25], there have been only a few reports on the N-substitution of isatin using asymmetric methods. Recently, Wolf’s group reported a transition-metal-catalyzed (Pd-catalyzed) asymmetric allylic

• enantioselectivity as the 0.1 mmol scale reaction (entry 14). Next, we investigated the substrate scope of the palladium-catalyzed asymmetric allylic amination of 1,3-diphenyl-2-propenyl acetate (12) with isatin derivatives 11 as nucleophiles under the optimized conditions using (aR)-(−)-6 as the ligand and Na3PO4

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

• the terminal alkene and the conformational strain of forming a bridge[3.2.1]bicycle might be responsible for a selective 6-exo-trig cyclization. From tricyclic compound 4, anti-Markovnikov oxidation catalyzed by palladium led to the formation of aldehyde 5. When treated with p-TsOH, the intramolecular

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

• followed by interception of the lithium enolate with PhNTf2 to give enol triflate 25 in 59% overall yield. The following palladium-catalyzed methoxycarbonylation produced methyl ester 26 in a satisfactory yield of 84%. TIPS-protected allylic alcohol 28 was selected as the appropriate precursor for the α,β

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

• , thereby offering unprecedented control over chemo-, regio-, and stereoselectivity parameters in catalytic manifolds. In 2015, the Jiang group developed a palladium-catalyzed regioselective three-component C1 insertion reaction (Scheme 1) [19]. In this reaction, an o-iodoaniline 1, phenylacetylene, and

• , tetrabutylammonium iodide (TBAI), and water significantly accelerated aryne generation, thereby increasing its local concentration. This favored aryne coordination to the palladium center, followed by CO insertion and reductive elimination to furnish phenanthridinones. In contrast, when dppm was introduced

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• reaction proceeded via an oxidative addition and reductive elimination processed in the presence of Ni(0), which was produced in situ from NiBr2 in the cathode. Palladium is one of the most important metals used as a catalyst in non-electrochemical reactions. In 2020, Budnikova et al. [58] reported a

• coupling reaction of phenylpyridine with dialkylphosphonate in the presence of palladium. It should be noted that the presence of palladium is an essential factor, and the results showed that the coupling reaction failed in the absence of palladium. Under pyridine-mediated conditions, the reaction follows

• a mononuclear palladacycle pathway, where a high electrolysis potential facilitates the formation of the ortho-phosphonate product with a favorable yield. On the other hand, when acid was used, forming a tetranuclear palladium intermediate led to the creation of a C−O−P bond. This reaction was

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

•  1, entry 3). When iron(II) sulfate (FeSO4) and iron trifluoromethanesulfonate (Fe(OTf)2) were used as the catalyst instead of copper(II) trifluoroacetate (Cu(TFA)2), the yields of the product were decreased (Table 1, entries 4 and 5). Using palladium(II) acetate (Pd(OAc)2) as the catalyst provided a

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• provide fluorophore 19. Subsequent palladium-catalyzed cross-coupling with tributyl(vinyl)tin resulted in the installation of the vinyl group (compound 20). Finally, cleavage of the silyl ether gave the free alcohol 21, which was converted into the corresponding mesyloxypropyl HBC ligand 22. The

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• was obtained by a Migita–Kosugi–Stille coupling between bromophenanthrene 15 and (E)-1,2-bis(tributylstannyl)ethene to afford diarylethene 18 followed by Mallory photoreaction. The obtained intermediate 18 contained residual palladium and isolation was not successful due to its poor solubility in

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

• inception (Scheme 1). Early studies were mainly focused on palladium catalysts [5][6][7][8], as demonstrated by the independent pioneering works of Tsuji and Trost in the 1960s and 1970s, respectively. While palladium catalysts demonstrated excellent reactivity with soft stabilized nucleophiles in the

• substitution reactions began to develop with the groundbreaking work of Takeuchi and Kashio, and subsequent research has revealed that iridium catalysts behave quite differently from their palladium counterparts [18]. The most notable distinction lies in their contrasting regioselectivity patterns. Palladium

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• [23]. Nevertheless, the arylation of monohalogenated N-acetyl diazocines via Stille coupling in our case gave unsatisfying results (Table 2). Reactions with tetrakis(triphenylphosphine)palladium(0) as catalyst resulted in no product 7 formation. Bis(tri-tert-butylphosphine)palladium(0) as catalyst

• -acetyl diazocine 22 under the conditions described by Hugenbusch et al. [37] showed no product formation and only starting material was isolated (Scheme 2). The palladium-catalyzed introduction of cyano groups under mild conditions in analogy to Iqbal et al. [38] gave the cyano-substituted N-acetyl

• of amino-N-acetyl diazocine by deprotection of the carbamate. Reaction conditions for the attempted Ullmann-type reaction with sodium azide. Reaction conditions for the palladium-catalyzed introduction of a nitrile functionality. Quantum yields of N-acetyl diazocine 1 in organic and aqueous media