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

• carbazoles. Scope of the method. Reaction conditions: 1 (0.2 mmol, 1.0 equiv), Pd2(dba)3 (0.02 mmol, 10 mol %), AgNO3 (0.24 mmol, 1.2 equiv), and 1,4-dioxane (2.0 mL) at 120 °C for 24 h. a10 mol % of Pd(OAc)2 was used instead of Pd2(dba)3. Gram-scale synthesis, directing group removal, and synthetic utility

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• synthesis [Pd(OAc)2, t-Bu2MePHBF4, Cs2CO3, and CsOPiv in toluene at 130 °C] was utilized to afford the C–H arylation in 78% yield with a 1:4 ratio of 68/69 [36]. Subsequent reduction of the pyridine N-oxide with Pd(OH)2/C and H2 followed by acidic Boc removal completed their total synthesis of complanadine

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

• is a kind of tetrose with biological and industrial relevance (Scheme 29). Waymouth et al. [109] reported the regio- and chemoselective oxidation of vicinal polyols using [2,9-dimethyl-1,10-phenanthroline = neocuproine)Pd(OAc)]2(OTf)2] (1) as catalyst. The formation of α-hydroxyketones occurs very

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• into (−)-xanthorrhizol (4) in seven steps. Later in 2003, they further accomplished the synthesis of (+)-heliannuol D, a sesquiterpenoid isolated from sunflower (Helianthus annuus L. SH-222), starting from 4 [28]. A three-step sequence transformed 4 into diol 5. Treatment of 5 with Pd(OAc)2 and

• removal of the benzyl group, chemoselective N-alkylation with fragment 196, and removal of the benzoyl group allowed the conversion of 195 into iodide 197. Sequential oxidation of the alcohol, HWE reaction, and reduction of the resulting ester then provided compound 198. In the presence of Pd(OAc)2, PPh3

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

• could be viewed as the aza[14]metacyclophane derivatives, in which two benzene rings are replaced by two pyrenes. The Pd-catalyzed arylation of 3a with Pd(OAc)2, PMe(t-Bu)2·HBF4 and DBU under microwave conditions gave two isomeric macrocycles MC1 and MC2 with four newly formed C–C bonds in yields of 5

• . Synthesis of N-doped macrocycles MC1, MC2, and MC3. Reaction conditions: a) Pd2(dba)3, Pt-Bu3·HBF4, NaOt-Bu, toluene, 110 °C, 24 h. 3a: 16%; 3b: 10%. b) Pd(OAc)2, PMe(t-Bu)2·HBF4, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), DMAc, microwave, 170 °C, 5 h. MC1: 5%; MC2: 90%; MC3: 85%. Supporting Information

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

• ). However, the diastereoselectivity is modest (1.7:1), likely resulting from insufficient chiral induction during the indolinone-forming step. Moving forward, this strategy was applied in the construction of axial chirality by the same group. In 2021, they reported a Pd(OAc)2/L2-catalyzed imidoylative

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

• metallation deprotonation mechanisms mediated by common catalysts like Pd(OAc)2. Our methodology not only identifies potential activation sites but also addresses the limitations of existing models by including a broader range of directing groups and reaction conditions while maintaining moderate

• , 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

• module [18]. Similarly to previous works [9][14], we focus on the CMD step, the first and commonly the rate-determining step in C–H activation, and consider the prototypical Pd(OAc)2 catalyst. Using a selective approach, we calculate the relative energies of all relevant palladacycle intermediates using

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

• under the same conditions. The advantage of XPhos Pd G2 is the use of an aqueous solution without inert conditions, but even under these conditions, the conversion was lower than in DMF. Pd(OAc)2 showed the lowest conversion by far, with no conversion observed when Et3N was used as the base. Overall

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

• optimized for the reaction of 3a with p-toluidine to give pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione 4a (Table 1). For the first experiment, we chose Pd(OAc)2 (5 mol %) as the catalyst, XPhos (5 mol %) as the ligand and K3PO4 (3 equiv) as the base in DMA (100 °C, 15 hours), which previously proved to be

• /hydroamination reaction. Synthesis of 4a–m. Conditions: Pd(OAc)2 (5 mol %), DPEphos (5 mol %), K3PO4 (3 equiv), DMA, 100 °C, 15 h. Yields of isolated products. Optimization of the synthesis of 4a. Photophysical data of 4a, 4j, 4k, 4l, and 4m in dichloromethane (c = 1·10−5 M) at 20 °C. Supporting Information

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• a subsequent Suzuki cross-coupling reaction with (4-(diphenylamino)phenyl)boronic acid was performed. The reaction conditions were adapted from prior experiments with C-NBD1 [40] and further refined for the heterocyclic analogues. Optimal results were achieved using K2CO3, Pd(OAc)2 and RuPhos with

• %; furan, 45 °C, 24 h, 84%; N-Boc-pyrrol, 90 °C, 68 h, 53%; ii) (4-(diphenylamino)phenyl)boronic acid (1.2 equiv), K2CO3, Pd(OAc)2, RuPhos, 4:1 toluene/H2O, 80 °C , 18 h. Overview of the new NBD derivatives and the isomerization products (QCs) expected upon isomerization. Formation of N-QC1 and N-QC2 could

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 acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• that benzofuran adduct 15c was previously reported by Dyker to be obtained in only 10% yield when 12 was reacted with 10 equivalents of unsubstituted benzofuran, in the presence of 5 mol % of Pd(OAc)2 at 100 °C for 3 days [52]. The compatibility of five-membered nitrogen heterocycles with our

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• Abstract The C–H arylation of 2-quinolinecarboxyamide bearing a C–Br bond at the N-aryl moiety is carried out with a palladium catalyst. The reaction proceeds at the C–H bond on the pyridine ring adjacent to the amide group in the presence of 10 mol % Pd(OAc)2 at 110 °C to afford the cyclized product in 42

• ), tetrabutylammonium bromide (31.7 mg, 0.098 mmol), Pd(OAc)2 (2.2 mg, 10 mol %), and triphenylphosphine (2.8 mg, 10 mol %). The mixture was dissolved in 3.1 mL of DMA and stirring was continued at 110 °C for 24 h. Then, water (3 mL) was added after cooling to room temperature. The product was extracted with

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• C‒F bond to give predominantly the trans product, but this pathway competes with a less favourable SN2 nucleophilic attack by fluorine to form the cis product. However, a mechanism entirely mediated by the I(III) HVI reagent, with the Pd(OAc)2 only acting as a Lewis acid to activate the HVI reagent

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• )] [40]. Introduction of the tert-butylperoxy fragment into the allylic position of substituted cyclohexenes 6 was carried out using Pd(OAc)2 in ambient conditions (Scheme 5) [41]. The corresponding allylic peroxy ethers 7 were synthesized in 62–75% yields, the key intermediate was proposed to be L2Pd(OO

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• molecules. 1.3.6 Pd-assisted anodic oxidation. In 2023, Ackermann and coworkers reported a Pd-catalyzed anodic oxidation for the alkenylation of arenes without the need for directing groups [57]. Using Pd(OAc)2 as the catalyst, 2-methyl-2-(phenylthio)propanoic acid as the ligand, and 1,4-benzoquinone (BQ

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

• as [MCM-41-2N-Pd(OAc)2] [130] and Pd-SH-silica bound catalysts [131] have also been successfully employed in this three-component pyrazole synthesis. Interestingly, the latter catalyst system does not require a copper cocatalyst. Tang's research group further extended polymer synthesis by using the

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• ) [101][102]. Our group attempted to use (E/Z)-1,2-difluoroethylene in a Heck reaction [78]. The experiments were performed using 4-iodotoluene or methyl 4-iodobenzoate in DMF, Pd(OAc)2 as a catalyst, and Et3N as a base (Scheme 25). The reactions were carried out in a stainless steel autoclave at 120 °C

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• bromide gave 4. With quinoline 4 in hand, we studied palladium-catalysed Sonogashira reactions with phenylacetylene (5a). Gratifyingly, our initial test reaction, using Pd(OAc)2 as catalyst with XPhos as ligand, gave bis-alkynylated product 6a in quantitative yield. Reducing the catalyst loading from 5 to

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• , PPh3, DIAD, 1,4-dioxane, 50 °C, overnight, i) (R = Et) NaOH, H2O, EtOH, 75 °C, 3 h, j) (R = allyl) Et3SiH, PPh3, Pd(OAc)2, ACN, rt, k) H–ʟ-Tyr–OMe, HOBt, EDCI, TEA, DCM, DMF, rt, 12 h, l) LiOH⋅H2O, H2O, 1,4-dioxane, rt, 45 min. Cy = cyclohexyl. Synthetic pathway to pyridone derivatives 3a–c of HeE1

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• the presence of K2CO3 (3 equiv) as base, an isonitrile (1.2 equiv), and Pd(OAc)2 (10 mol %) which in situ undergoes a reduction to Pd(0) (Scheme 2). Another example was published by Wu's group, who carried out the synthesis of 1-(1H-indol-1-yl)-2-arylethan-1-one derivatives by promoting the formation

• of amides from 2-alkynylanilines by using TFBen (benzene-1,3,5-triyl triformate) as a CO source, Pd(OAc)2, DPEPhos (bis[(2-diphenylphosphino)phenyl] ether), and DIPEA (N,N-diisopropylethylamine) in MeCN. After 24 h, Pd(OAc)2 and AlCl3 were added to promote a selective cyclization reaction [14]. The

• selective cyclization to the indole derivative in the presence of Pd(OAc)2 and AlCl3. A variety of indole derivatives were synthetized in good isolated yields (Scheme 3). Synthesis of indoles by Pd(II)-catalyzed carbonylation reaction Oxidative carbonylation reactions, as well as all other types of

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

•  1). However, neither one of these new ligands performed better than L1 (see Table 1 below). In an attempt to enhance the protocol performance, we also evaluated the palladium source as indicated in Table 1. Switching Pd(TFA)2 by Pd(OAc)2 led to a minor increase in the yield, but without any changes

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• first examined by using 10 mol % Pd(OAc)2, 20 mol % PPh3, 2 equiv of Et3N in CH3CN or DMF at 105 °C for 24 h under N2 atmosphere. However, the reactions failed under these conditions (Table 1, entries 1 and 2). When K2CO3 was used as a base to replace Et3N, the reactions in either CH3CN or DMF for 3 h

• ., PCy3 and P(o-tol)3 reduced the yield of the desired product 6a (Table 1, entries 7 and 8). Lowering the amount of Pd(OAc)2 or changing the reaction temperatures resulted low yields of 6a (Table 1, entries 9–11). Similar results were observed from the reactions using other bases, such as K3PO4, NaOAc

• to use 1 mmol of 5a with 10 mol % Pd(OAc)2 and 20 mol % PPh3, 2 equiv of K2CO3 in 3 mL CH3CN at 105 °C for 3 h under N2 atmosphere which afforded product 6a in 70% yield (Table 1, entry 3). The combination of an initial multicomponent reaction with post-condensation reactions in one-pot is a good

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• , DMF/H2O, 60 °C, 18 h. (b) Pd(OAc)2, PPh3, CuI, phenylacetylene, Et3N, 50 °C, 5 h. (c) CuI, neocuproine, 4-MeOC6H4SH, NaOt-Bu, toluene, 110 °C, 13 h. (d) CuI, ʟ-proline, DMF, 80 °C, 14 h. (e) CuI, imidazole, Cs2CO3, DMF, 120 °C, 15 h. (f) 3-Methoxy-2-(trimethylsilyl)phenyl triflate, CsF, MeCN, rt, 18 h