Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• Heck coupling: In 2003, Snieckus and co-workers [97] have synthesized the seco-C/D ring analogues of ergot alkaloids through the intramolecular Heck reaction as a key step. The coupling precursors 63 and 68 were prepared from 4-bromoindoles by a sequential Vilsmeier–Haack, Henry nitroaldol condensation

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• Chemistry of New Materials NAS Belarus, 220141, Minsk, Belarus Department of General and Inorganic Chemistry, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia 10.3762/bjoc.11.41 Abstract An environmentally friendly Matsuda–Heck reaction with arenediazonium tosylates has been developed

• ; diazonium salts; Matsuda–Heck reaction; microwave-assisted synthesis; stilbenes; Introduction Diazonium salts are known as one of the most valuable building blocks in organic synthesis [1]. Today, their most common use is the construction of carbon–carbon bonds in palladium-catalyzed reactions. Starting

• with the work of Matsuda’s group [2], who used a diazonium salt as a high-reactive electrophile for a Heck reaction, the Matsuda–Heck reaction does require the addition of neither bases nor ligands and is carried out under very mild conditions [3]. Furthermore, diazonium salts are more often prepared

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

• Matthieu Jouffroy,
• Rafael Gramage-Doria,
• David Sémeril,
• Dominique Armspach,
• Dominique Matt,
• Werner Oberhauser and
• Loïc Toupet

Beilstein J. Org. Chem. 2014, 10, 2388–2405, doi:10.3762/bjoc.10.249

• study dealing with the Mizoroki–Heck reactions, comparative tests were carried out with WIDEPHOS, a diphosphine analogue of HUGPHOS-2. Keywords: asymmetric hydroformylation; cyclodextrin; Heck reaction; homogeneous catalysis; palladium; phosphine; rhodium; Introduction Since the studies of Fu

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• derivative under palladium-catalyzed conditions. The benzoyl ester of BtOH has been evaluated in a decarboxylative Pd-mediated Heck reaction, leading to a modest product yield [36]. However, this appears to be the only example of a BtOH derivative in Pd-mediated reactions. In principle, formation of π–allyl

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• -dimethylaminopyridine, pyridine, 25 °C; then KOAc, MeOH, 64 °C, 85% yield for the two steps) to give 8. Generation of an enol triflate from the carbonyl group in 8 (potassium hexamethyldisilazide, phenyl bis-triflimide, THF, −20 → −10 °C, 85% yield) set stage for a Heck-reaction with methyl acrylate (cat. Pd(OAc)2, cat

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• Abstract A novel class of chiral phosphanyl-oxazoline (PHOX) ligands with a conformationally rigid cyclopropyl backbone was synthesized and tested in the intermolecular asymmetric Heck reaction. Mechanistic modelling and crystallographic studies were used to predict the optimal ligand structure and helped

• the isomerization were identified. It was shown that the nature of this isomerization is different from that demonstrated previously using chiral diphosphine ligands. Keywords: asymmetric catalysis; chiral phosphine ligands; cyclopropane; Heck reaction; organophosphorus; transition metal catalysis

• ; Introduction The asymmetric Heck reaction is one of the most powerful and versatile processes for the enantioselective construction of new carbon–carbon bonds. Intramolecular versions of this reaction catalysed by palladium complexes with BINAP and related diphosphine ligands [1][2] allow for efficient

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• 21 in 52% yield. The fused indoline motif was formed via an intramolecular Heck reaction under Fu’s conditions [41] to provide a mixture of two olefinic regioisomers 22, which were converted to saturated fused indoline 23 under standard catalytic hydrogenation conditions in a combined yield of 40

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• , 43500 Semenyih, Selangor Darul Shsan, Malaysia 10.3762/bjoc.9.325 Abstract The palladium metal catalysed Heck reaction of 4-iodoanisole with styrene or methyl acrylate has been studied in a continuous plug flow reactor (PFR) using supercritical carbon dioxide (scCO2) as the solvent, with THF and

• the reaction with methyl acrylate the reactor was scaled from a 1.0 mm to 3.9 mm internal diameter and the conversion and turnover frequency determined. The results show that the Heck reaction can be effectively performed in scCO2 under continuous flow conditions with a palladium metal, phosphine-free

• Suzuki, Kumada, and Heck reactions. Among these, the palladium-catalysed Heck reaction [2] is one of the most explored families of such reactions. In the Heck reactions, a vinylic hydrogen is replaced by a vinyl, aryl or benzyl group through reaction with a halide compound. This reaction has been

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• chloride 110 gave 111, which upon sequential oxidation yielded enaminone 112. Finally, the isoindolinone moiety was generated via an intramolecular Heck reaction using tetrakis(triphenylphosphine)palladium(0) and thallium acetate, to give magallanesine (97) in excellent yield [85]. Aporphine alkaloids: The

Palladium(II)-catalyzed Heck reaction of aryl halides and arylboronic acids with olefins under mild conditions

• Tanveer Mahamadali Shaikh and
• Fung-E Hong

Beilstein J. Org. Chem. 2013, 9, 1578–1588, doi:10.3762/bjoc.9.180

• -rich and electron-poor olefins, were converted smoothly to the targeted products in high yields. Compared with the existing approaches employing SPO–Pd complexes in a Heck reaction, the current strategy features mild reaction conditions and broad substrate scope. Furthermore, we described the coupling

• of arylboronic acids with olefins, which were catalyzed by Pd(OAc)2 and employed N-bromosuccinimide as an additive under ambient conditions. The resulted biaryls have been obtained in moderate to good yields. Keywords: aryl halides; Heck reaction; olefins; palladium-complex; phosphine; Introduction

• the synthesis of leading molecules, a variety of preparative methodologies have been developed. Particularly, the Heck reaction is one of the most chosen methods in the synthesis of aryl-substituted olefins [7][8][9]. Aryl halides or arylboronic acids are among the most commonly employed arylpalladium

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• directly in another synthetic step. For example, in a recent multistep flow synthesis of branched aldehydes from aryl iodides [98], an in-line aqueous extraction step following an ethylene-Heck reaction allowed the intermediate styrene products to be carried directly into a subsequent downstream

• hydroformylation reaction. Without the extraction step the hydroformylation step was unsuccessful; experiments suggested that this was due to the amine base or its salts. In the reactor configuration used in this work (Figure 32), the output from the ethylene-Heck reaction is combined with an aqueous stream to

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• efforts on method development toward the efficient construction of velbanamine-type indole alkaloids. As shown in Scheme 2, an intramolecular Heck reaction (via 9-exo manner) would finalize the 9-membered ring, which was biogenetically derived from a retro-Mannich reaction from catharanthine (Scheme 1

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• /Heck reaction starting from N-acryloylanilides [38]. The use of metal catalysis, especially of palladium, has played a major role in the construction of 3-alkenylindolin-2-ones [38]. Despite significant progress in approaches for the construction of 3-alkenylindolin-2-ones, use of complicated

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• development of palladium chemistry [4]. The catalytic cycle starts with the oxidative addition of Pd(0) to generate a σ-arylpalladium(II), then a rapid insertion of a double or triple bond takes place [5]. This method was particularly applied in the “Mizoroki–Heck reaction” [6] for the synthesis of

• competitive protonation of the fragile intermediate alkylnickel 2-Ni. While the Pd-catalyzed reductive Heck reaction promoted by a hydride generated in situ is well known [23][24], the nickel-catalyzed process is likely to occur through a radical hydrogen transfer from the DMF [20][25]. The N-allylaniline 1c

N-Heterocyclic carbene–palladium(II)-1-methylimidazole complex catalyzed Mizoroki–Heck reaction of aryl chlorides with styrenes

• Ting-Ting Gao,
• Ai-Ping Jin and
• Li-Xiong Shao

Beilstein J. Org. Chem. 2012, 8, 1916–1919, doi:10.3762/bjoc.8.222

• )-Im] complex 1 was found to be an effective catalyst for the Mizoroki–Heck reaction of a variety of aryl chlorides with styrenes. Both activated and deactivated aryl chlorides work well to give the corresponding coupling products in good to excellent yields by using tetrabutylammonium bromide (TBAB

• ) as the ionic liquid. Keywords: aryl chloride; Mizoroki–Heck reaction; N-heterocyclic carbene; palladium complex; synthetic method; Introduction The palladium-catalyzed reaction between organic halides and alkenes, the Mizoroki–Heck reaction, is one of the most versatile methods for the formation of

• carbon–carbon bonds [1][2][3][4][5][6][7]. Usually, in order to achieve the highest efficiency of the palladium-catalyzed Mizoroki–Heck reaction, toxic, air-sensitive and expensive phosphine ligands are introduced to facilitate the corresponding transformations [8][9]. In order to overcome the drawbacks

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• spiro-products 17 and 18 (Scheme 13). The sole formation of the annulated indole 18 as a single diastereoisomer suggests a mechanism that is strictly closer to the classical oxidative Heck reaction (pathway B) rather than to a Wacker-type reaction (pathway A). In fact, the formation of the product 18 is

Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide

• Suri Babu Madasu,
• Nagaji Ambabhai Vekariya,
• M. N. V. D. Hari Kiran,
• Badarinadh Gupta,
• Aminul Islam,
• Paul S. Douglas and
• Korupolu Raghu Babu

Beilstein J. Org. Chem. 2012, 8, 1400–1405, doi:10.3762/bjoc.8.162

• acetate [9] this affords (R)-1-acetyl-5-[2(phenylsulfonyl)ethyenyl]-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole (12), under Heck reaction conditions. Deacetylation of (12) by using potassium carbonate affords (R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole (13). Reduction of

• palladium on carbon (Scheme 5). The contamination of this impurity in eletriptan hydrobromide (1) was 0.10–0.20%. This impurity can be controlled by tightening up the in-process control of the N-acetyl bromoindole pyrrolidine during the Heck reaction. During the initial process development of eletriptan

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• used. A proper choice of catalyst and reaction conditions is also needed to improve the efficiency of each reaction (Scheme 18) [18]. Consecutive one-pot transformations initiated by Heck reaction and terminated by intramolecular aza–Michael addition were developed by Hanson and coworkers to access a

Evaluation of a commercial packed bed flow hydrogenator for reaction screening, optimization, and synthesis

• Marian C. Bryan,
• David Wernick,
• Christopher D. Hein,
• James V. Petersen,
• John W. Eschelbach and
• Elizabeth M. Doherty

Beilstein J. Org. Chem. 2011, 7, 1141–1149, doi:10.3762/bjoc.7.132

• (Figure 7). It should be noted that Kappe observed a “Pd mirror” due to soluble Pd leaching from a CatCart® during a continuous flow Mizorki–Heck reaction [24]. In comparison, the fine black precipitate seen in our wash experiment is more consistent with solid Pd/C catalyst. The experiment was repeated

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• of 1.0 mm i.d. coil) was “loaded” with Pd by processing ≈2 mL of the Mizoroki–Heck reaction mixture through the coil under reaction conditions (180 °C, 1.6 mL/min flow rate) with 1 mol % of the Pd(OAc)2 as pre-catalyst. As expected, the desired product 14 was obtained in 94% isolated yield after

• relatively low (Table 2, entries 1 and 2), significantly higher levels of Pd were found in samples derived from the Mizoroki–Heck reaction mixture (Table 2, entry 3). These results, both in terms of decreasing conversion and Pd leaching are therefore analogous to the experiments using Pd/C as a heterogeneous

• . Only renewed loading of the coil by running a Mizoroki–Heck reaction with Pd(OAc)2 or by simply processing a Pd(OAc)2 solution through the coil at elevated temperature regenerated the “palladated” stainless steel coils. Influence of pressure on reaction rate in flow reactors In the resistively heated

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• sulfonamides, all prepared in high yields. As this route employs sulfonamide-stabilised anions the preparation and handling of unstable sulfonyl chloride intermediates is therefore circumvented (Scheme 14) [17]. An analogous Heck reaction approach has also been employed to introduce a homologous side chain as

• eletriptan (Scheme 20). A rather ingenious Mitsunobu coupling reaction has been used to create a highly functionalised substrate 96 for an intramolecular Heck reaction resulting in a very short and succinct synthesis of eletriptan and related analogues 97 [29] (Scheme 21). Interestingly, it was found that

• serotonin 5-HT3 receptor antagonist ondansetron (119, Zofran). In this synthesis a palladium-catalysed intramolecular Heck-reaction was used to build the tricyclic indole core in a short and concise sequence (Scheme 26) [35][36]. Alternatively, a direct Fischer indole synthesis between phenylmethyl

Studies on Pd/NiFe₂O₄ catalyzed ligand-free Suzuki reaction in aqueous phase: synthesis of biaryls, terphenyls and polyaryls

• Sanjay R. Borhade and
• Suresh B. Waghmode

Beilstein J. Org. Chem. 2011, 7, 310–319, doi:10.3762/bjoc.7.41

• reactions was demonstrated [40]. The most important paradigm of this reaction is the easy removal of catalyst from the reaction mixture by employing an external magnetic field. We recently reported the filtration-free magnetically separable Pd/NiFe2O4 catalyst for the Heck reaction [41]. Herein, we report

Pd-catalyzed decarboxylative Heck vinylation of 2-nitrobenzoates in the presence of CuF₂

• Lukas J. Gooßen,
• Bettina Zimmermann and
• Thomas Knauber

Beilstein J. Org. Chem. 2010, 6, No. 43, doi:10.3762/bjoc.6.43

• ][18]. We developed a process in which benzoic acids are activated by esterification with electron-poor phenols with the loss of water [19]. The esters are then subjected to a decarbonylative Heck reaction to yield vinyl arenes, CO and the phenols, which can be used in further reaction cycles. In a

• related approach, the benzoic acids activated as isopropenyl esters undergo a decarbonylative Heck reaction that yields the vinyl arenes along with CO and acetone [20]. Since no base is added, only volatile by-products are generated instead of waste salts, and the amount of solvent can be minimized. Myers

• and co-workers introduced another version of the Heck reaction in 2002, in which they converted mostly electron-rich aromatic carboxylic acids and alkenes to vinyl arenes with the release of CO2 [21][22][23]. This decarboxylative Heck reaction allows the direct conversion of benzoic acids without

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• oxidation and an intramolecular Heck reaction [149]. Exposure of the quinone 207 to sunlight triggered the formation of benzoxazole 208, which cleaved to form an intermediate iminium salt. Subsequent proton transfer gave the vinylogous carbamate 209 (Scheme 57). After oxidation of the hydroquinone to the