Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• ]. Results and Discussion Chemical syntheses The synthetic strategy is very similar to the one previously developed for the preparation of DB18 and designed analogues (Scheme 1) [23][24]. It starts from known quinazoline 1 which, on Buchwald–Hartwig-type reaction with 3-bromoaniline (2a), gave

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

• intricate and inefficient using these standard synthetic protocols. The transition-metal-catalyzed C–N bond formation has emerged as a viable route to access non-symmetric azobenzenes, owing to the broad functional group tolerance of Buchwald–Hartwig amination reactions [34][35][36][37][38][39][40]. Kong

• for synthesizing non-symmetric azobenzenes via a Pd-catalyzed cascade involving C–N coupling of arylhydrazines with aryl bromides, followed by oxidative dehydrogenation (Figure 1c). As our study was nearing completion, Váňa and co-workers disclosed a related Buchwald–Hartwig approach employing the Pd

• reported in Buchwald–Hartwig reactions, enhances yield by facilitating the reduction of Pd(II) to Pd(0) and improving the solubility of the base [56]. To ensure the generality of the conditions, 1-bromo-2-(trifluoromethoxy)benzene was also tested, yielding the desired azobenzene 3c in 69% yield with the

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

• bromide (see Supporting Information File 1). Subsequent Buchwald–Hartwig reaction with 1,3-dibromo-7-tert-butylpyrene (2) gave the [2 + 2] macrocyclic precursors 3a,b as the major product in 16%/10% yields, and trace amounts of higher oligomers as detected by mass spectrometry. Notably, compounds 3a,b

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• classical Buchwald–Hartwig amination reaction [16] or the Ullman reaction [17][18]) which require pre-functionalisation steps and harsh conditions [19]. Many protocols for C–H aminations have been applied to heteroaromatic compounds, mainly 5-membered heteroarenes, and a great deal of attention has been

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

• , Howell et al. recently disclosed a general method for the synthesis of 2-halomethylideneoxetanes through halogenation of 2-methylideneoxetanes using N-halosuccinimides, and illustrated their synthetic utility by Suzuki–Miyaura, Sonogashira and Buchwald–Hartwig coupling reactions [53]. In addition to Cu

• Suzuki coupling to tether the oxetane with the nucleophile, and gave moderate to high yields (Scheme 48b). The last one employed an Ullman or Buchwald–Hartwig coupling and provided access to various benzomorpholines 203 with good functional group tolerance (Scheme 48c). In 2020, Sun et al. reported a

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

• performance to Cs2CO3 including the lack of methyl ester hydrolysis, but a lower price. The catalyst's performance had a more significant influence on the reaction results than the base. Both phosphine catalysts as well as the second generation of the Buchwald–Hartwig catalyst [47][48] gave similar results

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

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• and excellent yield of 94% (Scheme 1). A chemoselective deprotection of the mannosyl thioacetate 7 to yield the glycosyl thiol 8 was achieved using 0.95 equivalents of sodium carbonate. The crude product was in turn submitted to a Buchwald–Hartwig–Migita cross-coupling reaction [33] with the

• azobenzene derivative 9 [34] to furnish 10. This reaction had to be carried out at −78 °C in order to suppress nucleophilic substitution of the ortho-fluorine substituents in 9 by the thiol 8, a reaction that competes with the desired cross-coupling. For the second Buchwald–Hartwig–Migita cross-coupling, the

• -dithio-ᴅ-threitol) [36] (Scheme 2A). The crude thiol 14 was subsequently subjected to a Buchwald–Hartwig–Migita cross-coupling reaction with the literature-known azobenzene thioglucoside 15 [37], resulting in the (6-thioglucosyl)mannoside 16 in 63% yield over two steps. Zemplén deacetylation [38] gave

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

• -substituted diazocines were prepared via Stille, Suzuki, and Buchwald–Hartwig reactions. X-ray structures are presented for derivatives 1, 2 and 7. Keywords: cross-coupling; diazocine; N-acetyl diazocine; photoisomerization; photoswitch; thermal relaxation; Introduction Diazocines are frequently used

• with bis(pinacolato)diboron did not lead to the formation of the pinacolborane-substituted N-acetyl diazocine 18. Accordingly, the Suzuki–Miyaura reaction with inversed roles between N-acetyl diazocine boronic acid pinacol ester and aryl or alkyl halides could not be investigated. The Buchwald–Hartwig

• amination is a versatile and powerful tool for C–N bond formation and widely applied in the synthesis of new pharmaceutical substances [29][30][31]. Furthermore, azobenzenes [32][33], as well as diazocines [34][35], have been derivatized via Buchwald–Hartwig amination. The Buchwald–Hartwig amination of

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• , thereupon highlighting potential for broad applications in photoredox catalysis on an industrial scale. In this context, T. Rovis et al. have studied a C–N cross-coupling Buchwald–Hartwig-like reaction using dual nickel and osmium catalysis under red-light activation, addressing common challenges such as

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• Buchwald–Hartwig aminations [16][17][18][19], Suzuki couplings [16][17][20], N-alkylations [21], hydroxylations [22], and photochemical reactions [23][24][25][26][27][28][29]. The versatility to handle multiple reagents and the widespread availability of 96-well plates have facilitated the extensive

• medium for enhancing the optimization of the Buchwald–Hartwig amination intermediate, which is crucial for synthesizing the drug olanzapine [47]. The reactor setup was integrated with spectroscopic and chromatographic in-line analytical tools, enabling real-time monitoring of products and reaction

• selection, a dispensing module for solids and liquids, a reaction module capable of heating and stirring, a sample preparation module, and a LC–MS characterization module (Figure 2d). The efficiency of the system has been demonstrated in three reactions types, namely Suzuki–Miyaura coupling, Buchwald

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• post-modification reactions. Examples of these reactions include the Ugi/Dieckmann reactions, Ugi/Robinson–Gabriel reactions, Ugi/Buchwald–Hartwig reactions, Ugi reaction followed by a catalytic aza-Wittig cyclization, Ugi reaction followed by SNAr strategy, Ugi/Heck reactions, Ugi/Huisgen

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

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

• attractive results in this area. Keywords: Buchwald–Hartwig coupling; cytotoxicity; heterocycles; Pd catalysis; quinazolines; Introduction Nitrogen-containing heterocyclic molecules are ubiquitous in living systems. Among them, quinazolines, and especially the 4-aminoquinazolines (type A molecules, Figure

• afforded the known aldehyde 2 in 65% yield [13]. Then, reaction with guanidinium carbonate in DMA at high temperature [12], gave the desired intermediate 2-aminobenzo[h]quinazoline (3). In a final step, classical Buchwald–Hartwig coupling [14][15][16][17] with bromobenzene under the conditions described

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• the residence time to 12.36 min amplified the error to approximately 8% (Figure 7c). A similar increase in error with prolonged residence time was noted in Kappe et al.’s kinetic modeling of the Buchwald–Hartwig amination reaction [41], where the theoretical and experimental values diverged by 4.1

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

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• are of substantial importance for the fine chemical industry, pharmaceuticals, agrochemicals, dyes, and natural products [25]. The synthesis of amine derivatives can be accomplished using many powerful techniques, including Buchwald–Hartwig and Ullmann cross-coupling reactions, hydroamination

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• functionality as well as Buchwald–Hartwig amination involving aryl halides. Thermal studies Thermal stabilities of DCPQs 1a–6a and DPQDs 1b–7b were evaluated using thermogravimetric analysis (TGA; Figure 2 and Table S4 in Supporting Information File 1). The thermal stability of the DCPQs is attributed to their

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald–Hartwig (B–H) or Chan–Lam (C–L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)6 as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and

• dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst. The synthetic utility of this novel strategy was showcased by demonstrating a formal synthesis for the antipsychotic drug clozapine and to an anticancer triazole–DBDAP hybrid. Keywords: Buchwald–Hartwig

• review in 2018 focused on a variety of routes to these compounds [8]. The well-known Buchwald–Hartwig (B–H) and Chan–Lam (C–L) reactions have proven to be highly useful procedures that allow the step-economical synthesis of diverse biologically relevant heterocycles through C–N bond formation [9]. These

The effect of dark states on the intersystem crossing and thermally activated delayed fluorescence of naphthalimide-phenothiazine dyads

• Liyuan Cao,
• Xi Liu,
• Xue Zhang,
• Jianzhang Zhao,
• Fabiao Yu and
• Yan Wan

Beilstein J. Org. Chem. 2023, 19, 1028–1046, doi:10.3762/bjoc.19.79

• chromophores, which are coupled through a Buchwald–Hartwig coupling reaction (another NI-PTZ paper) [39]. The oxidation of the PTZ unit was readily performed by treatment with H2O2 as oxidant (Scheme 1). All compounds were obtained with satisfactory yields and the molecular structures were fully characterized

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• synthesised via a copper-catalysed Ullman-type coupling or a palladium-catalysed Buchwald–Hartwig amination (Scheme 9). Performing the rearrangement at high temperatures resulted in the undesirable formation of acridine byproducts 44. Cleaner reaction profiles could be obtained at a lower temperature (100 °C

• categorised according to the major or final catalytic step employed to form the 7-membered heterocycle as several synthetic methods use multiple catalytic steps. 3.1 Buchwald–Hartwig amination, etherification and thioetherification The Buchwald–Hartwig reaction gives access to arylamines, -ethers and

• -pyridobenzazepines 60b via cyclisation of 2,2'-dihalostilbene analogue 58 through a Pd-catalysed double Buchwald–Hartwig amination. The stilbene analogues 58 were prepared by a Wittig reaction with reported yields of the desired Z-isomer around 55%. The amination step was performed on a series of primary alkylamines

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• synthetic strategy, which itself was synthesized from Br-DiKTa [28] following a Buchwald–Hartwig coupling. Details of the synthesis are found in Supporting Information File 1. The identity and purity of the molecules were verified using a combination of 1H and 13C NMR spectroscopy, high resolution mass

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• transformations. Thus far, mechanochemical palladium-catalyzed cross-coupling reactions such as Suzuki–Miyaura [34][35][36][37][38][39][40][41][42][43][44][45][46][47], Buchwald–Hartwig [48][49][50][51][52], Sonogashira [53][54][55][56], Negishi [57], Mizoroki–Heck [58][59][60], and C–S bond-forming [61

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• -9H-carbazol-9-yl)-5-methyl-2-methylthiopyrimidine (tCbz-mPYR) as a starting material for the synthesis of 2-substituted pyrimidine emitters (Scheme 1). Compound tCbz-mPYR was synthesized by using the palladium-catalyzed Buchwald–Hartwig amination reaction of 4,6-dichloro-5-methyl-2-methylpyrimidine

Comparative study of thermally activated delayed fluorescent properties of donor–acceptor and donor–acceptor–donor architectures based on phenoxazine and dibenzo[a,j]phenazine

• Saika Izumi,
• Prasannamani Govindharaj,
• Anna Drewniak,
• Paola Zimmermann Crocomo,
• Satoshi Minakata,
• Leonardo Evaristo de Sousa,
• Piotr de Silva,
• Przemyslaw Data and
• Youhei Takeda

Beilstein J. Org. Chem. 2022, 18, 459–468, doi:10.3762/bjoc.18.48

• mono-functionalized compound DBPHZ-OTf, the target compound 1 was successfully synthesized through a Pd-catalyzed Buchwald–Hartwig amination with phenoxazine (POZ) in a good yield as red-brown solid (Scheme 1). The D–A–D counterpart POZ-DBPHZ was synthesized according to the previously reported process