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

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

• (TFE) as a solvent, yielding 2,2,2-trifluoroethyl pyrazole-5-carboxylates 72 (Scheme 25) [103]. A limitation of the method is that methanol formed in the first reaction step also reacts with the acid chloride to produce unwanted byproducts. The carbonylative Heck coupling of aryl bromides with butyl

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• interconvertible to each other by hydration or dehydration, i.e., a plausible precursor of the allylic alcohol would be the diene, and vice versa [90]. Since both 8 and 10 are easily obtainable from 2 by Mozoroki–Heck coupling with commercially available 2-methyl-3-buten-2-ol, ester hydrolysis (LiOH in THF/H2O

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

• –Heck coupling Whereas Arnold et al. [30] reported the preparation of dibenzo[b,f]heteropines via consecutive Heck and Buchwald–Hartwig reactions (Scheme 11), amination may also precede the introduction of the double bond (Scheme 17). The formation of the dibenzo[b,f]heteropine skeleton by means of a

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -metal catalysts, such as in the Suzuki–Miyaura and Heck coupling reactions. Methodologies for forming different C–C bonds have recently been developed in the field of single-electron chemistry [63][64][65]. Considering that EDA-complex-initiated free-radical reactions are carried out under mild

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• . Therefore, the synthesis of inthomycin A was advanced in the racemic form. Treatment of compound (rac)-17 with aqueous ammonia gave the corresponding amide (rac)-18 in 96% yield. Heck coupling between (rac)-18 and vinylboronate pinacol ester [31] using Pd(PPh3)4/Et3N conditions provided stereoselective

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• Mining and Materials Engineering, McGill University, Montreal, Quebec H3A 0E9, Canada 10.3762/bjoc.16.201 Abstract In this report, chitin and chitosan nanocrystals were used as biomass-based supports for Pd nanoparticles (NPs) used as a heterogeneous catalyst for the Heck coupling reaction. By using a

• one-pot fabrication method, a Pd salt precursor was directly reduced and deposited onto these nanocrystal catalysts. Characterization of these nanocomposites showed disperse Pd NPs on the surfaces of the chitinous nanocrystals. Heck coupling model reactions revealed full product yield in relatively

• deposit Pd NPs directly onto both ChNCs and ChsNCs, and the as-made heterogeneous catalysts were tested with the Heck coupling reaction as a model for catalytic activity. Findings The fabrication of ChNC and ChsNCs was conducted using a procedure previously reported by our group (Lam) (see Supporting

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• Scheme 10. Very recently, the groups of Nimura and Arisawa reported the synthesis of a phenyl C-glucoside derivative of spliceostatin beginning from ᴅ-glucal (Scheme 12) [35]. A Heck coupling of the tris(trimethylsilyl) ether of 74 with phenylboronic acid in the presence of Pd(OAc)2 and benzoquinone (BQ

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• , thus rendering this methodology well suitable for the synthesis of a variety of indole derivatives. Subsequently, the panel of oxidative Heck coupling reactions via a photoredox catalytic system combined with C–H activation using Rh [74] or Ru [75] was extended by Rueping’s group. In 2014, Rueping

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• , numerous methods for the synthesis of these compounds have been developed, examples are the Pechmann condensation [10][11], Stille coupling reaction [12], Knoevenagel condensation [13], Heck coupling reaction [14], Kostanecki reaction, Baylis–Hillman reaction [15], Michael reaction [16], Suzuki–Miyaura

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• available naphthalene-2-ylboronic acid or (3,4-dihydronaphthalen-2-yl)boronic acid (Scheme 1). The latter was synthesized according to a literature procedure [36]. Formation of compounds 2b–h was accomplished through Heck coupling of aryl bromides with the appropriate styrenes (Scheme 2) [37]. Compounds 2b

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• Suzuki, Sonogashira and Heck coupling reactions (Scheme 48). The reaction proceeded by the formation of 1-iodoalkyne 142 which was characterized by mass and 1H NMR spetra. This iodoalkyne then formed a complex of Cu(I) with 2-AP. This was followed by migratory insertion of haloalkyne to form reactive Cu

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• , followed by addition of bromide 5a, potassium phosphate and PdCl2(dppf)2 in DMF at 85 °C for 3.5 h gave the coupled product 10 in 47–63% yields (Scheme 3). In contrast to the case of the Heck coupling products (6 and 8, Scheme 2), nitrile 10 underwent facile reduction with lithium aluminium hydride. The

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• chemistry), POSS are often functionalized through the chemical processes of C=C bond transformation, e.g., hydrosilylation, Heck coupling, silylative coupling and olefin metathesis. Olefin metathesis, i.e., catalytic exchange of double bonds between carbon atoms, is a powerful tool in organic synthesis. The

• subsequently modified via Heck coupling with a set of 4-substituted styrenes to give the next generation of functionalized derivatives. The authors also demonstrated the possibility of further functionalization of an amino-substituted derivative via the reaction with 3,5-dibromo or dinitrobenzoyl chloride. The

• of vinylsilanes (Scheme 1). The possibility to modify vinyl and styryl derivatives of silsesquioxanes via Heck reaction has been proved. The Heck coupling of 4-bromostyrene and vinyl-POSS derivatives leads to the formation of oligomeric products containing a silsesquioxane core in the polymer

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• (hydroarylation) is a 100% atom economical process to build fundamental alkyls and alkenes (Scheme 2) [42][43][44][45]. It is an efficient alternative to C–H alkylation reactions with alkyl halides where one equivalent of salt waste was released, and dehydrogenative Heck coupling with alkenes for the synthesis of

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• Namitharan has very recently demonstrated that a one-pot palladium-catalyzed Heck coupling allows for transferring the aryl group of (diacetoxyiodo)arenes released after a metal-free methylenation reaction (Scheme 45) [110]. The latter that is performed by reacting PhI(OAc)2 with DMSO, applies to amidines 97

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• then oxidized to the sulfoxide G by iodosoarene C via the postulated activated sulfoxide F, releasing one equivalent of aryl iodide 2. A Chugaev-type elimination yields the olefin H, which finally affords acrylamidine 35 via Heck coupling with the iodoarene 2 with 50% AE (for R1 = H, R2 = Bn, Ar1 = Ar2

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• the efficient synthesis of benzotropone 11 in a good isolated yield (83%) via PdNPs@EDACs-catalyzed Heck coupling and intramolecular condensation of 2-bromobenzaldehyde (46) and methyl vinyl ketone (47) (Scheme 10) [58]. 2.2. Reactions of 4,5-benzotropone (11) 2.2.1. Reactions via the carbonyl group

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• , PR China 10.3762/bjoc.14.66 Abstract A mechanically-activated chemoselective Heck coupling for the synthesis of 3-vinylindazoles has been developed with the aid of catalytic amounts of TBAB and NaBr as both dehalogenation restrainer and grinding auxiliary. After tuning of the chemical conditions and

• [33][34] and axitinib [35][36][37][38] (Scheme 1). Mechanochemistry as a burgeoning technique to promote solvent-free reactions has led to remarkable advances [39][40][41][42], particularly for cross-coupling reactions [43][44][45], involving Heck coupling with the aid of stoichiometric amounts of

• -2H-pyran-2-yl)-1H-indazole (3q) in 90% yield. Next, sequential two-step Heck coupling and Migita coupling under ball milling conditions selectively afforded THP-axitinib 7. Finally, deprotection of 7 with p-TsOH gave axitinib in a total yield of 44% (41% [66]). Comparing to previous synthetic

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• mol % Na2PdCl4, Pd/L = 1:1 (molar ratio), 1.5 mL H2O, 100 °C. Reusability of the Na2PdCl4/L1 catalytic system for the catalytic Mizoroki–Heck coupling reaction of 4-bromoacetophene (1a) and styrene (2a). The synthetic route for the preparation of imidazolium salts L1–L3. Optimizing the reaction

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• Mizoroki–Heck coupling reactions under microwave irradiation (MW) were carried out with a colloidal Pd nanocatalyst stabilized with poly(N-vinylpyrrolidone) (PVP). Many stilbenes and novel heterostilbenes were achieved in good to excellent yields starting from aryl bromides and different olefins. The

• particular, Pd NPs have been well-established as catalysts in the Mizoroki–Heck coupling reaction, obtaining the desired products in good to high yields, finding some examples in aqueous solution and under microwave (MW) irradiation [26][27][28][29][30][31][32][33][34][35][36]. Besides these studies, there

• organic reactions could be increased, and better selectivities of the products achieved, but also the homogeneous mixing of the reactants in water could be enhanced, on the basic of the efficient ability to absorb MW energy by water [44]. The use of water in combination with MW heating for Heck coupling

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• , ICP–MS and XPS suggest that Pd/MgAl-LDHs have excellent textural properties with zero-valence Pd on its layers. The reaction results indicate that the catalyst could be utilized in HSBM systems to afford a wide range of Heck coupling products in satisfactory yields. Furthermore, this catalyst could be

• Information File 1). The Heck coupling reaction under HSBM conditions m-Bromoacetophenone (1a) and styrene (2a) were chosen as the model reactants (Scheme 2), catalyzed by Pd/MgAl-LDHs under ball-milling conditions with silica gel (5 g) and stainless-steel balls (ΦMB = 0.2, dMB = 14 mm) at 800 rpm. Based on

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• synthesis, also on highly elaborate substrates. Considerable efforts were invested before the challenging Heck coupling with the thiazole fragment 6 could be effected with useful selectivities. Besides the desired E,E-diene 34 formation of other double bond isomers both in the southern and northern part of

• reactions to set both the characteristic assemblies of neighbored methyl and hydroxy group bearing stereogenic centers. In addition, an aldol condensation was shown to enable an efficient route for construction of a delicate triene system. The final E-selective Heck coupling on a highly elaborate substrate

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• the Mizoroki–Heck coupling. We were aware that we would perhaps face a greater challenge in terms of generating the desired 6-membered exocyclic product rather than the undesired 7-membered endocyclic product [18]. Starting from commercially available propargylamine, tosylated compound 1 was prepared

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• [36] in Heck reactions [37][38][39][40][41][42] is also of interest, since these coupling products are useful intermediates for the synthesis of non-proteinogenic amino acids [43]. To our delight, the Heck coupling of syn-4a and 16 could be efficiently achieved employing Jeffery´s conditions [44