A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• was chosen DMF, although the use of polar aprotic solvents usually leads to products of the oxidative Heck reaction. The authors noticed a significant reduction of Pd(II) to Pd(0) (by secondary processes such as oxidative homocoupling or oxidation of boronic acid to the corresponding phenol). The Pd(0

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• catalysts in various organic reactions [1] such as the Ullmann coupling, Suzuki coupling, Suzuki–Miyaura coupling, and the Heck reaction. Aside from being useful synthetic agents, biguanides gained particular interest from the perspective of medicinal chemistry. For the first time, the biological activity

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

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• ]isoquinolines. The multicomponent reaction was combined with one-pot reactions to make a synthetic method with good pot, atom and step economy. MeCN was used as a preferable green solvent for the reactions. Keywords: [3 + 2] cycloaddition; Heck reaction; hexahydropyrrolo[2,1-a]isoquinoline; one-pot reactions

• evaporating unreacted 3-bromopropene (7) from the reaction mixture, crude product 8a was used for developing the intramolecular Heck reaction by screening Pd(II) catalysts, ligands, bases, additives, solvents, temperatures and reaction time (Table 1). The initial intramolecular Heck reactions were carried out

• , entry 3). Other attempts to improve the Heck reaction using different ligands, such as (P(o-tol)3, PCy3 and dppm, were not successful (Table 1, entries 4–6). The reaction at 105 °C in MeCN gave 9a in 78% yield (Table 1, entry 7), while at 120 °C in DMF gave 9a in 77% yield (Table 1, entry 11). Reducing

Suzuki–Miyaura cross coupling is not an informative reaction to demonstrate the performance of new solvents

• James Sherwood

Beilstein J. Org. Chem. 2020, 16, 1001–1005, doi:10.3762/bjoc.16.89

• the key fundamental principles of boron and palladium speciation and the role of the base in the Suzuki–Miyaura reaction. For researchers developing safer solvents, the Mizoroki–Heck reaction is a more suitable cross-coupling methodology to demonstrate solvent performance [28]. The reaction kinetics

• Mizoroki–Heck reaction and hence there is also a motivation to investigate safer alternative solvents that the Suzuki–Miyaura reaction lacks. If researchers are still compelled to study the utility of solvents in the Suzuki–Miyaura reaction, I encourage future studies to be directed at challenging

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• Pd-catalysed Fujiwara–Moritani or oxidative dehydrogenative Heck reaction via dual C–H activation [21][22][23][24]. One of the early examples of this reaction, reported by Gaunt and co-workers, involved the regioselective, solvent-controlled C3 alkenylation of indoles with alkenes containing electron

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• ]pyridine ring has been synthesized via the microwave-assisted Mizoroki–Heck reaction. The efficient modification of the imidazo[1,2-a]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor. Keywords: α

• -phosphonoacrylates; α-phosphonopropionates; imidazo[1,2-a]pyridine; microwave-assisted reaction; Mizoroki–Heck reaction; Introduction In the last few decades, the Mizoroki–Heck reaction has become one of the main tools in organic synthesis. Its use for the functionalization of a wide range of compounds cannot be

• confirmed by the presence in a number of pharmaceuticals [2][3]. The imidazo[1,2-a]pyridine-ring modification via Pd-catalyzed reactions is broadly reported in the literature [3], however, such functionalizations for more complex molecules are not very common. On the other hand, the Mizoroki–Heck reaction

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

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

• and 2e were obtained in moderate yield using 3a as the aryl halide in the Heck reaction. The use of 3b in the Heck reaction resulted in a substantial improvement of yield in the synthesis of 2g but not for 2c. Interchanging the roles by using 5-vinylnicotinamide (5a) or methyl 5-vinylnicotinate (5b

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

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• . The reduction of OX7 followed by elimination to OX21 proceeded smoothly and as subsequent transformation a Heck reaction with alkenyl nonaflate 10 was performed delivering OX22. The conversion of OX7 to alkyne OX23 applied the protocol of Lyapkalo et al. [59] using Schwesinger’s base [60] as crucial

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

• 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

Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones

• Xiaochen Du,
• Jianjun Huang,
• Anton A. Nechaev,
• Ruwei Yao,
• Jing Gong,
• Erik V. Van der Eycken,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2018, 14, 2572–2579, doi:10.3762/bjoc.14.234

• synthesis of 2-quinolones using either intramolecular Heck reaction [60] or Knoevenagel condensation [61][62]. Results and Discussion We began our study with the preparation of the model substrate 7a through the Ugi reaction of tetrolic acid (3a), benzaldehyde (4a), tert-butyl isocyanide (5a) and 3,5

Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• involving catalytic C–C bond construction with the double bond of terminal alkenes (e.g., Heck reaction, hydrometalation followed by functionalization, carbometalation, and olefin metathesis) [10][11][12][13]. However, direct C–C bond formation of the allylic C(sp3)–H bond adjacent to double bonds has

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

• catalytic domino reactions. The group of Hayashi has reported in 2004 the first example of the transformation of a cyclic diaryl-λ3-iodane, for which both Ar–I bonds are used in a palladium cross-coupling reaction [56]. It relies on a double Heck reaction performed with methyl vinyl ketone in the presence

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

• values (66% for 33b) are obtained. In another tandem procedure, a metal-free C(sp3)–H olefination of amidines 34 with DMSO and PIDA derivatives 20b was developed by Namitharan and co-workers [49]. A Pd(II)-catalysed Heck reaction of the formed exocyclic double bond with the emerging iodoarene yields

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

• highly efficient route for the synthesis of axitinib. Keywords: axitinib; ball-milling; dehalogenation; Heck reaction; indazoles; Introduction The palladium-catalyzed vinylation of alkenes in the presence of a base, known as the Heck reaction (Mizoroki–Heck reaction), is one of the most important

• . Currently, the Heck reaction is usually carried out by adding an excess of phase-transfer catalyst such as tetrabutylammonium bromide (TBAB) or tetrabutylammonium iodide (TBAI) to increase the reaction yield under both solvent-heating [19][20][21][22][23] and solvent-free conditions [24][25][26][27

• reaction pathway for this Heck reaction under mechanical ball milling conditions was proposed. As shown in path a, (Scheme 4). The reaction proceeded through Heck cross coupling, where a catalytic amount of TBAB was enough to stabilize the Pd(0). However, the oxidative addition intermediate I was unstable

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• of alkynes has also been explored as an alternative approach for C–H alkenylation [10]. Despite the significant progress made, each of these C–H alkenylation manifolds has some critical limitations. For example, the dehydrogenative Heck reaction is often limited to activated monosubstituted alkenes

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• (CF3SO2)2Zn, which demonstrated great efficiency in introducing the CF3 moiety on (hetero)aromatic rings [34]. Trifluoromethylation of olefins: In 2005, Vogel and co-workers showed that terminal alkenes could be trifluoromethylated by means of CF3SO2Cl via a palladium-catalysed desulfitative Mizoroki–Heck

• reaction, in classical solvents or in an ionic liquid media, to yield the corresponding CF3 alkenes (Scheme 28) [35][36]. As for Yu, Zhang and co-workers, they described the trifluoromethylation of two enamides under photocatalytic conditions, using similar conditions as those they proposed for the

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• % of PCy3·HBF4 along with an excess K2CO3–MeOH led to biaryls within 99 min and with a yield up to 97% (Scheme 8) [57]. Heck reaction Frejd and co-workers reported the first mechanochemical Heck reaction [58]. Su and co-workers demonstrated that (E)-stilbene derivatives were synthesized by the coupling

• . Easy purification procedures, towards quantitative conversion and minimum byproducts are additionally considered to be major significance to this method. Tullberg et al. investigated the Mizoroki–Heck reaction between iodobenzene and the methyl ester of N-Boc-protected aminoacylate under different

• ]. Mechanochemical Suzuki reaction [56]. Mechanochemical Suzuki–Miyaura coupling by LAG [57]. Mechanochemical Heck reaction [59]. a) Sonogashira coupling under milling conditions. b) The representative example of a double Sonogashira reaction of p-iodoacetophenone with 1,4-bis-ethynyl benzene. Copper-catalyzed CDC

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

• 10,000. Keywords: aqueous homogeneous catalysis; Mizoroki–Heck reaction; Na2PdCl4; PEG-functionalized imidazolium salts; Introduction Nowadays, both increasing environmental concerns and drastic commercial competition are the driving forces to develop more sustainable and economic processes for

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

• make this protocol a great option for stilbene syntheses by Mizoroki–Heck reaction. Keywords: aqueous reaction medium; MAOS; Mizoroki–Heck reaction; Pd nanoparticle; sustainable organic synthesis; Introduction Palladium-catalyzed reactions have emerged as an important tool for organic synthesis

• both coupling partners. The Mizoroki–Heck reaction and related chemistry occupy a special place among the basic types of Pd-catalyzed reactions, particularly the vinylation of aryl/vinyl halides or triflates [7][8][9][10], explored not only in the inter- and intramolecular version [2][11][12][13], but

• also in domino [14] and asymmetric catalytic processes [15]. Due to its versatility, the Mizoroki–Heck reaction is extensively employed in the synthesis of pharmaceutical, agrochemical and natural products, and continues to attract attention within the synthetic chemists’ community [16][17][18]. From

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

• easily recovered and reused for at least five times without significant loss of catalytic activity. Keywords: ball milling; Heck reaction; layer double hydroxides; solvent-free; supported Pd catalyst; Introduction High-speed ball milling (HSBM)-assisted transition metal-catalyzed cross-coupling reactions

• of the coupled products with unacceptable Pd species led to a hard separation and recycling of homogeneous catalyst systems. In our previous study [4] we reported a ball-milling Heck reaction catalyzed by Pd(OAc)2. Although the catalyst showed the satisfactory reactivity, it was difficult to recover

• at 800 rpm. Optimization of Heck reaction conditions.a Examination of grinding auxiliaries on yield of 3aa.a Supporting Information Supporting Information File 242: Details of experimental procedures and characterization data of prepared compounds, 1H, 13C NMR, and MS spectra of all coupling

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

• suitable olefination strategy. Subsequently, for connecting the resulting fragment to the thiazole subunit 6 a Heck reaction was envisioned as part of studies advancing this type of Palladium-catalyzed coupling strategies in complex target synthesis [61][62][63][64][65][66]. Finally, a HWE-macrocyclization

• unambiguously confirming the stereochemistry of this macrolide [59]. Menche’s total synthesis of archazolid B One the methodological incentives of the synthetic campaign of the Menche group directed towards the archazolids were the further development and application of the Heck reaction in complex target

• archazolid A. Synthesis of archazolid B (2) by a ring closing Heck reaction of 38. Retrosynthetic analysis of archazolid B by the Trauner group. Synthesis of acid 40 from Roche ester 41 involving a highly efficient Trost–Alder ene reaction. Synthesis of precursor 39 for the projected relay RCM reaction