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

• deketalization afforded carbonate 58. A palladium-catalyzed decarboxylative alkenylation reaction was then carried out across the less hindered face of the six-membered ring to connect C5 and C6. Selective deprotonation and triflation at the C4 carbonyl group provided enol triflate 59. An intramolecular

• 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

• , generating an allylic alcohol that was acetylated in situ to provide 74. An Ireland–Claisen rearrangement facilitated the third olefin transposition, concurrently forming an all-carbon quaternary center at C9 and affording carboxylic acid 75. The fourth olefin transposition was achieved via a palladium

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• Zhao group employed a similar two-phase strategy to achieve the first total synthesis of the Ryania diterpenoid garajonone (8) in 2025 [56] (Scheme 10). Key achievements of this synthesis include: (1) application of palladium-catalyzed Heck/carbonylative cascade cyclization to efficiently construct the

• ). The synthesis commenced with the preparation of key cyclization precursor 98 via Barbier coupling and Babler–Dauben oxidative rearrangement. A pivotal palladium-catalyzed Heck/carbonylative cyclization then efficiently furnished the ABC tricyclic core 99. Notably, adding N-formylsaccharin under a CO

• atmosphere significantly suppressed side reactions, yielding the cyclized product in excellent yield and selectivity. This indicates that N-formylsaccharin, beyond acting as a CO-releasing agent, may function as a ligand in the catalytic cycle to regulate the palladium catalyst’s activity and stability

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• challenging due to the inherently higher reactivity at the C3/C6 positions. In this study, we report a palladium-catalyzed, directing group-assisted, regioselective C1–H nitration of carbazoles. The protocol features a removable directing group and is amenable to gram-scale synthesis. This strategy provides a

• ; palladium; Introduction Carbazole represents an important heterocyclic scaffold that is broadly present in many natural products, biologically active motifs, as well as optoelectronic and functional materials [1][2][3][4][5][6][7][8]. By virtue of its substantial application in various fields, significant

• nitration of carbazole is highly desirable [68][69]. In this context, we envisioned utilizing a directing group-assisted regioselective C–H activation strategy to achieve the C1-selective nitration of carbazole. Through our efforts, we identified a palladium-catalyzed reaction system for C1 nitration 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

• to construct a β-lactam, an α-metallated piperidine equivalent, overcoming poor yields and stereoselectivity in traditional methods. Its palladium-catalyzed cross-coupling with 2-bromolycodine via β-lactam C–C cleavage enabled stereoretentive coupling, efficiently synthesizing lycoplatyrine A and its

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• synthetic intermediates, and used to successfully modify diverse bioactive scaffolds via late-stage functionalization, collectively demonstrating the method’s synthetic utility. In 2025, the Das group developed a palladium-catalyzed cycloisomerization of 2-alkynylbenzoate-cyclohexadienone that enables

• solvent-controlled selective syntheses of two polycyclic compounds (Scheme 6) [13]. Using PdCl2 as the catalyst and DMF as the solvent, substrate 22 underwent a 6-endo-dig cyclization and subsequent enone insertion, forming a palladium–carbon bond intermediate. Protonolysis yielded isocoumarin-fused

• pathway changed significantly. The (E)-benzofulvene product 110 was exclusively generated through palladium-catalyzed C–H activation followed by a 5-exo-dig cyclization (Scheme 22, path b). This study established a general method for the divergent syntheses of phenylnaphthalenes and benzofulvenes from

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

• the presence of water, highlighting its robustness. Keywords: azo compounds; cross-coupling; domino catalysis; palladium; phosphine ligands; Introduction Azobenzenes are a widely studied class of compounds known for their distinctive photoresponsive properties, rendering them valuable in a variety

• as an oxidant, combined with NaH as the base, increased the formation of 3a, achieving GC yields of up to 65% (Table 1, entry 3). Control experiments demonstrated that palladium, phosphine, and base were all essential for this reaction (Table S4 in Supporting Information File 1). However, under

• azobenzenes; b) previous Pd-catalyzed methods for the synthesis of non-symmetric azobenzenes; c) this work: Pd-catalyzed dehydrogenative C–N coupling of arylhydrazine. a) Proposed catalytic cycle for the one-pot palladium-catalyzed dehydrogenative C–N coupling for the synthesis of azobenzene from

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

• for the oxidation of 1,2-diols, triols and tetraols using the chiral palladium-based catalyst 2 bearing a pyridinyl oxazoline (pyOX) ligand (Scheme 31) [110]. 5-Hydroxy-2(5H)-furanone (HFO) 5-Hydroxy-2(5H)-furanone (HFO) is an interesting C4 platform which is formed from furfural by oxidation. Han and

• the Lewis acidic Sn-Beta was also reported for this reaction providing succinic acid in 53% yield. Sn-Beta accelerated the Baeyer–Villiger oxidation of furfural to the 2(3H)-furanone intermediate by activating furfural (Scheme 45) [152]. Two methods, one using CO under palladium catalysis, and one

• generation of other hydrogenation products than in organic solvents [199]. Since this new route to CPN from furfural was reported in 2012, many catalysts have been proposed for promoting this reaction. Recent works include heterogeneous systems based on cobalt [200], nickel [201], copper [202] or palladium

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