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

• % yield. The yield is improved to 94% when the reaction is performed with PPh3 as a ligand of palladium. The reaction is examined with amides derived from unsubstituted picoline, 6-methylpicoline, and 2,6-pyridinedicarboxylic acid in a similar manner to afford the cyclized products in 70%, 77%, and 87

• % yield, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benzamides to afford multiply fused heterocyclic compounds in 81% and 89% yields, respectively. Keywords: intramolecular C–H arylation; multiply fused heterocycles; palladium acetate

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• cyclic derivatives. Conjugated imines are usually synthesized from the corresponding carbonyl precursors by reaction with a sulfonamide in the presence of Lewis acids and a dehydrating agent such as molecular sieves [3]. Also, recently a palladium-catalyzed dehydrogenation of aliphatic imines was

• ). Firstly, hydrogenation with palladium on carbon led to the formation of 55 in a good yield. Secondly, an alkylation of the NH of the indole followed by intramolecular cyclization led to tetracyclic derivative 56 in an 80% yield. Next, a deprotection of the azo nitrogen atom led to derivative 57 in a 92

• palladium on carbon led to free alcohol derivative 72 in a 98% yield. Next, a urea 73 and various thioureas 74–77 were obtained in good yields and with retention of the enantioselectivity, demonstrating the usefulness of the novel methodology for the synthesis of new organocatalysts. In April 2023, Huang

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

• products or stabilised by the tosyl group and subsequently attacked to form only the cis product in an SN2 reaction. Liu and co-workers reported a palladium-catalysed intramolecular aminofluorination of unactivated alkenes [27] (Scheme 2) in the presence of PhI(OPiv)2, AgF and MgSO4 as an oxidant, source

• ring A (Scheme 2). The Pd(II) intermediate is oxidised by PhI(OPiv)2/AgF, forming Pd(IV). Formation of the product can occur either by reductive elimination by Pd(IV) or SN2 nucleophilic attack by fluorine with concomitant palladium reduction. Reductive elimination of the Pd(II) intermediate forms the

• palladium catalyst. Aminofluorination of alkenes in the synthesis of enantiomerically pure β-fluorinated piperidines. PMB = para-methoxybenzene, athe ee value was determined after Cbz group was replaced with tosyl group, bthe value in brackets corresponds to the ee value after crystallization. PG

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

• aid of the ortho-directing group to give the palladium intermediate B, which undergoes reductive elimination to establish the C−C bond. A Cu-catalyzed difunctionalization of styrenes 211 with TBHP and N-hydroxyphthalimide (NHPI) (212) as sources of O-functional groups was reported (Scheme 66) [135

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• to good yields of the corresponding products. The vinyl boronates obtained from the aforementioned reaction were subsequently subjected to a Suzuki coupling with the remaining aryl iodides obtained from 16 in the presence of a palladium catalyst. This step facilitated the formation of functionalized

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• acids. We report on palladium-catalyzed coupling attempts on the ortho-, meta-, and para-meso-phenyl position of sterically demanding dodecasubstituted saddle-shaped porphyrins. While para- and meta-substitutions could be achieved, ortho-functionalization in these systems remains elusive. Furthermore

• further substitution directly on the meso- or a meso-phenyl ortho/meta/para positions of a porphyrin, is the introduction of C–C bond forming chemistry. This is typically achieved using palladium and/or another transition-metal catalyst [20]. Sonagashira [21], Suzuki–Miyaura [22], Heck [23], Stille [24

• ). Formation of palladium black was observed but product formation was also indicated by TLC and 1H NMR. For a final attempt at establishing reactivity with boronic acid 15 the temperature was increased to 110 °C and gave the desired anthracenylporphyrin 37 in a 32% yield. In the case of boronic acids with

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

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

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• Ruben Manuel Figueira de Abreu Peter Ehlers Peter Langer Universität Rostock, Institut für Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany 10.3762/bjoc.20.228 Abstract We report the synthesis of polycyclic uracil derivatives. The method is based on palladium-catalysed Sonogashira–Hagihara

• was studied by UV–vis and fluorescence spectroscopy. Keywords: cross-coupling; cyclization; heterocycles; palladium; Introduction Nucleobases contain the coded information and give DNA and RNA their typical structure. As a nucleobase, uracil is involved in numerous vital processes and is therefore a

• of palladium-catalysed Sonogashira–Hagihara and Suzuki–Miyaura cross-coupling reactions (Scheme 1). The final cyclisation step is accomplished by an acid-mediated cycloisomerisation. The synthesis of starting materials 4 was carried out by our previously reported protocol [65]. While compounds 4a–f

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• ) derivatives, which possess recognized pharmacological properties [12]. They used sequential reactions catalyzed by palladium and copper. The process involves an initial amination, which can be carried out via either the Buchwald–Hartwig or the Chan–Lam reaction, followed by a palladium-catalyzed

• terazosin and prazosin were successfully synthesized. Oliveira Jr. et al. developed a new methodology for the asymmetric synthesis of β-aryl-γ-lactam derivatives with very good yield and enantioselectivity [16]. This was achieved through a palladium-catalyzed Heck–Matsuda desymmetrization of N-protected 2,5

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• reagents have been developed. These reagents are easily being converted into multisubstituted fluoroalkenes through cross-coupling using palladium, nickel, copper, ruthenium, and manganese catalysts [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Hosoya and Niwa et al. published the

• First, we optimized the conditions of the Suzuki–Miyaura cross-coupling in reference to the report by Yang et al. (Table 1) [43]. Upon the treatment of multihalogenated vinyl ether 1a with phenylboronic acid 4a (1.3 equiv) and palladium diacetate (10 mol %) as a catalyst at 40 °C, Suzuki–Miyaura cross

• -coupling proceeded to produce fluoroalkene 2a in 50% yield (Table 1, entry 1). Increasing the amount of 4a to 2.0 equiv and decreasing the amount of palladium diacetate to 5 mol % improved the reaction yield (Table 1, entry 2). When the reaction mixture was heated to 60 °C or reflux conditions, 2a could be

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• should allow us to introduce the molecular diversity on the anilino moiety in the last step through a palladium-catalyzed reaction (Scheme 1). Therefore, we prepared first the core structure 3 in two steps from the commercially available fluoronaphthalene 1. Metallation, followed by trapping with DMF

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

• arenes via palladium-catalyzed electrooxidation, further showcasing the versatility and potential of this approach in organic synthesis (Scheme 42b) [58]. These methodologies underline the expanding role of palladium catalysis in electrochemical transformations, offering robust strategies for the

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• conditions (as mentiond above), they worked well for the photoinduced radical cyclization of o-diisocyanoarenes (Scheme 18d) [39]. The obtained quinoxaline-2,3-diphosphines 28 are promising ligands for transition metal catalysts such as palladium catalysts. Aza-Bergman cyclization of o-alkynylaryl

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

• accessible. Aryl iodides undergo conversion to the corresponding alkynones in aqueous ammonia through a palladium-catalyzed carbonylative coupling with terminal alkynes under 1 atm of carbon monoxide. Building upon this discovery, these intermediates were cyclized with hydrazines to give pyrazoles 121 in a

• aliphatic alkynes, copper iodide is necessitated as a co-catalyst [141]. In addition to classic Sonogashira catalysts, phosphane-free palladium [Pd(NN)] chelate complexes can also be used, which promote excellent regioselectivity [142]. A variation of the reaction is possible with Mo(CO)6 as a carbon

• palladium-catalyzed oxidative carbonylative Sonogashira alkynylation and cyclocondensation with arylhydrazines [144]. In 2009, Müller and co-workers introduced an alternative approach for synthesizing alkynones through a one-pot process [145]. Azulen-3-ylalkynones 126, obtained by glyoxylation of azulene

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• within 4 h in the dark, irradiation with blue light halves the reaction time for many compounds. Overall, these observations are in line with those of Alcazar et al. [43]. In their work, the authors demonstrated the formation of a complex between palladium and the organozinc reagent which is absorbing in

• the blue region. This complex then accelerates the oxidative addition of the aryl halide to the metal, which is usually the rate-limiting step for palladium-catalyzed cross-couplings. Based on these results we decided to perform all Negishi reactions under blue light irradiation. With the optimized

• subsequent re-esterification was necessary to achieve the desired ketoester. Reduction of the oximes Oximes are commonly reduced to the corresponding amines using either palladium on activated carbon and hydrogen gas [65][66][67][68], or with zinc and a Brønsted acid as source of hydrogen [68][69]. Both

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• metal reagents, including cobalt [10], copper [11], rhodium [12][13][14], palladium [15][16][17], silver [18], and gold [19] catalysts, have been reported. However, compared to the widespread use of metal catalysts, the synthesis of isoquinolinone scaffolds mediated by environmentally friendly

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• photochemical reactions under acidic conditions, which were proposed to proceed via radical cations [20]. Since electrochemical and photochemical aza-Wacker cyclizations can offer ring systems that are difficult to construct through state-of-the-art palladium-catalyzed methods, the mechanistic understanding of

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

• comprising a GBB-3CR and a palladium-catalyzed azide-isocyanide coupling to generate imidazo[1,2-a]pyridine-fused 1,3-benzodiazepines 85 (Scheme 27). The GBB reaction smoothly proceeded using 2-azidobenzaldehydes 83, 2-aminopyridines and isocyanides as the precursors. The in situ-generated azides 84 were

• then reacted with a different isocyanide (R4–NC) in the presence of a palladium catalyst. The release of nitrogen from intermediates I resulted in nitrenes II, which in turn involved in the intramolecular transfer to yield species III. The carbodiimides IV, which were formed through reductive

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• steroidal 17-ketones were first alkylated in the presence of the lithium derivative of ethyl propiolate. After stereoselective formation of the corresponding adduct, the triple bond was chemoselectively reduced under catalytic hydrogenation using 5% palladium on charcoal. As a final step, a p

• reaction of mestranol acetate (34) catalysed by a palladium(II) complex, in the presence of p-benzoquinone under carbon monoxide. The authors propose an initial addition of the acetate C=O group onto the triple bond coordinated to palladium, followed by a MeOH attack onto the resulting oxycarbenium, and a

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• secondary alcohol of 21, the utilization of another variant, MoBsc9 L110A, Y112R, generated through the directed evolution of MoBsc9, facilitated the optimal conversion in the corresponding oxidative allylic rearrangement to afford brassicicene I (9) in 64% yield. Further palladium-catalyzed allylic

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• cyanoborohydride as a mild reducing agent, and paraformaldehyde as a methylating agent [36]. Methanol can be used as the methylating reagent in other methods. Here, a palladium on carbon (Pd/C) catalyst processes the dehydrogenation of the alcohol to form the corresponding aldehyde. The subsequently formed imine

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• monofluorination radiolabelling using [18F]NFSI. Electrophilic fluorination of benzylic C–H bonds has been demonstrated as a powerful approach. However, these techniques can be constrained to defined substrate classes and the requirement of using strong bases. Palladium catalysis Palladium-catalysed chemistry is

• pioneering report into palladium(II)/(IV)-catalysed C–H fluorination of 8-methylquinolines using N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate as an electrophilic “F+” source under microwave conditions (Figure 5) [39]. Benzylic fluorination was achieved in good yields on three examples, each bearing

• -(trifluoromethyl)aniline in conjunction with external ligand 5 facilitated the formation of a series of fluorinated α-amino acids. Xu and co-workers also disclosed a palladium-catalysed protocol for the fluorination of simple benzylic substrates bearing a bidentate directing group (Figure 8) [42]. Yields varied

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• . Therefore, alternative procedures for homo-coupling reactions using other transition-metal catalysts such as palladium, nickel, manganese, and iron have been developed [5][6][7][8][9][10][11][12][13]. In recent years, transition-metal-free coupling reactions have also been developed for environmentally

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• chromatographic purification due to much lower solubility of 4b compared to 4a. The metal complex of 4b with copper(II) was prepared, because copper(II) exhibited better extraction and separation abilities than cobalt(II) and palladium(II) in the case of Cu-tethered rectangular nanobrackets 1a [11]. Before SWNT

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

• /bjoc.20.107 Abstract Three bis- or tris-brominated 2-trifluoromethylquinolines have been successfully applied in palladium-catalysed Sonogashira reactions, leading to several examples of alkynylated quinolines in good to excellent yields. Optical properties of selected products have been studied by

• steady state absorption and fluorescence spectroscopy which give insights of the influence of the substitution pattern and of the type of substituents on the optical properties. Keywords: alkynes; catalysis; fluorescence; heterocycles; palladium; Introduction Quinoline is a well-known core structure

• 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