Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• desired DVCPR in almost quantitative yield at elevated temperature, followed by removal of the silyl-protecting group under acidic conditions to furnish cycloheptenone 70. Standard functional group interconversion furnished diolefin 71. Subjection of this compound to Heck coupling conditions resulted in

• in the formation of a bridged tetracycle after initial Heck coupling followed by carbo-palladation and subsequent β-hydride elimination [69][70][71]. Double bond regioisomers (between C7 & C8 or C13 & C14) were obtained. Oxidation with DDQ yielded the 1,6-unsaturated ketone 72. Selective epoxidation

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

• ; flow chemistry; Heck; palladium; supercritical carbon dioxide; Introduction The use of cross-coupling reactions between organometallic reagents and organic halides as a straightforward method of carbon–carbon bond formation has gained much popularity over the past three decades. The development of

Copper-catalyzed trifluoromethylation of alkenes with an electrophilic trifluoromethylating reagent

• Xiao-Ping Wang,
• Jin-Hong Lin,
• Cheng-Pan Zhang,
• Ji-Chang Xiao and
• Xing Zheng

Beilstein J. Org. Chem. 2013, 9, 2635–2640, doi:10.3762/bjoc.9.299

• reagents, it was proposed that the transformation might proceed via a radical, electrophilic or Heck-type process (Scheme 2) [47][48][49][50]. We reasoned that even if the reaction involved the radical process (path A, Scheme 2), the radical intermediate could still be oxidized to a cation because

• electrophilic trifluoromethylation reagents can be considered as an oxidant. In the presence of base, both of the cation and Heck-type intermediates should be able to undergo hydrogen elimination to form a Cvinyl–CF3 bond. On the basis of these reports and our hypothesis, we commenced to examine the reaction of

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• , and this simple procedure allowed for the functionalization of various N–H as well as variously N-protected indoles with almost complete selectivity for the 2-position, even in the case of “naked” indoles (Table 16). The same group also reported on two examples of Heck-type copper-catalyzed

Oxidative 3,3,3-trifluoropropylation of arylaldehydes

• Akari Ikeda,
• Masaaki Omote,
• Shiho Nomura,
• Miyuu Tanaka,
• Atsushi Tarui,
• Kazuyuki Sato and
• Akira Ando

Beilstein J. Org. Chem. 2013, 9, 2417–2421, doi:10.3762/bjoc.9.279

• aldehydes in the presence of fluoride anion [29]. Recently, Prakash et al. [30] reported the synthesis of β-trifluoromethylstyrenes through a Heck coupling reaction of aryl iodides with 1-iodo-3,3,3-trifluoropropane, allowing a direct introduction of 3,3,3-trifluoropropenyl groups to aromatic rings

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• -catalyzed oxidative lactonization or an intramolecular cyclization reaction of δ-ketoaldehydes [12], a ruthenium-catalyzed aerobic oxidative cyclization of aromatic acids with alkynes [13], an FeCl3-promoted regioselective annulation of o-(1-alkynyl)benzoates with disulfides [14], a Heck–Matsuda cyclization

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• delivered the best results with yields of up to 89%. For the reaction mechanism we assume that the palladium(0) inserts into the C(sp2)–Br bond to form a Pd(II) species. A sequence of two carbopalladation reactions form a triene system which is able to cyclize by a Heck-type reaction, a 6π

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

• step [84]. In 1996, Kurihara (Scheme 13) reported a [1,2]-Meisenheimer rearrangement followed by an intramolecular Heck cyclization to elaborate the isoindolobenzazocine moiety [85]. The synthesis commenced with the preparation of ester 106 from piperonal according to a known procedure [86]. A four

• 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

Synthesis of enones, pyrazolines and pyrrolines with gem-difluoroalkyl side chains

• Assaad Nasr El Dine,
• Ali Khalaf,
• Danielle Grée,
• Olivier Tasseau,
• Fares Fares,
• Nada Jaber,
• Philippe Lesot,
• Ali Hachem and
• René Grée

Beilstein J. Org. Chem. 2013, 9, 1943–1948, doi:10.3762/bjoc.9.230

• –Miyaura coupling [35] gave biphenyl derivative 7e in 82% yield, while the Heck [36] and Sonogashira [37] reactions afforded also the desired targets 8e and 9e in 72% and 77% yield respectively. Similar results were obtained in Pd-mediated reactions starting from pyrroline 6e, as indicated in Scheme 8. 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

• Tanveer Mahamadali Shaikh Fung-E Hong Department of Chemistry, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung, Taiwan (R.O.C.) 10.3762/bjoc.9.180 Abstract A series of general and selective Pd(II)-catalyzed Heck reactions were investigated under mild reaction conditions. The first

• -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

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

• hydride-AIBN initiated radical cyclization [33][34]. In 2005, Player and co-workers reported a tandem Heck/Suzuki–Miyaura coupling process for the synthesis of (E)-3,3-(diaryl)oxindoles [35][36][37]. Recently, alkenylation of indolin-2-ones has been developed by palladium-catalyzed aromatic C–H activation

• /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

• skeleton was achieved by using NiBr2bipy catalysis. Keywords: alkenes; carbometallation; carbonickelation; cyclization; Heck-type reaction; nickel catalysis; Introduction Carbometalation is a reaction involving the addition of an organometallic species to a nonactivated alkene or alkyne to form a new

• 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

• the most promising metallic substitutes [11]. However, the tedious preparation of Ni(0) complexes such as Ni(cod)2 explains that nickel chemistry is hardly perceived as a realistic alternative to palladium, except in electrochemical processes [12][13]. Nevertheless, some nickel-catalyzed Heck

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• synthesis. Thus, the development of simple methods concerning such vinylation reactions of phenols always remains an important process. Mizoroki–Heck-type reaction could be considered as an efficient procedure for the synthesis of such vinylated phenols [18][19]. There are a number of reports available in

• the literature that involve Pd-catalyzed cross coupling reactions of various aryl halides with different olefins. However, the major drawback of the Mizoroki–Heck-type reaction in the synthesis of 1,1-disubstituted olefins rests on its poor selectivity toward the formation of α-products [20][21][22

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

Iridium-catalyzed intramolecular [4 + 2] cycloadditions of alkynyl halides

• Andrew Tigchelaar and
• William Tam

Beilstein J. Org. Chem. 2012, 8, 1765–1770, doi:10.3762/bjoc.8.201

• reactions to gain access to complex bicyclic molecules that would not be accessible directly by cycloaddition. Previous work has demonstrated this synthetic utility by the further functionalization of 2a by Pd-catalyzed Suzuki and Heck coupling reactions [33]. In theory any of the cycloadducts 2 could

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• aziridination. A range of ortho-, meta- and para-substituted cinnamates were synthesised via Wittig, Heck or esterification routes (for details, see Supporting Information File 1). Each substrate was subjected to two sets of aziridination conditions, with the optimum yields reported. Electron-rich substrates

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

• easily removed from IV by the anion formed from the initial palladium salt with generation of the 3-indolyl-palladium complex V, which evolves a Heck-type reaction to give the 3-alkenylindoles 1. Conversely, the deprotonation of the C-3 position is difficult in acidic medium, favoring the transfer of

• 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

• -alkenylated indoles 27. The pyrimido[3,4-a]indole skeleton 29 was proven to be accessible by intramolecular 6-exo-trig cyclization of the N-alkenylindole 28 with PdCl2(MeCN)2 as catalyst and 1,4-benzoquinone as oxidant in THF/DMF at 80 °C (Scheme 16) [51]. Catalytic oxidative Heck reactions allowed also the

Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

• Esteban P. Urriolabeitia,
• Eduardo Laga and
• Carlos Cativiela

Beilstein J. Org. Chem. 2012, 8, 1569–1575, doi:10.3762/bjoc.8.179

• further elimination of a methyl group by 1,2-shift of the Me unit from the N atom to the Pd centre, as previously reported by Heck et al. [20]. As we have shown previously in Scheme 3, in the presence of nucleophiles the process results in the formation of conformationally restricted glutamate derivatives

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

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• results in the liquid phase, ortho,ortho-unsubstituted nitroarenes also delivered indole moieties in good yields. Subsequent palladium-catalyzed reactions (Suzuki, Heck, Sonogashira, Stille) delivered, after cleavage, the desired molecules in moderate to good yields over four steps. The scope and

• contrast to their liquid-phase counterparts. However, they gave a mixture of products (Supporting Information File 1). The next stage is the functionalization by cross-coupling reactions. In our first communication, we employed Suzuki and Heck reactions [24]. In addition to these reactions, Stille

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• and Heck reactions, respectively [21]. The dienes obtained during these transformations were successfully converted in Diels–Alder reactions to afford carbocyclic chiral compounds with a sugar backbone. In 2008, Gagné introduced a Ni-mediated Negishi coupling to synthesize alkyl- and aryl-C-glycosides

Branching out at C-2 of septanosides. Synthesis of 2-deoxy-2-C-alkyl/aryl septanosides from a bromo-oxepine

• Supriya Dey and
• Narayanaswamy Jayaraman

Beilstein J. Org. Chem. 2012, 8, 522–527, doi:10.3762/bjoc.8.59

• acceptor moieties in C–C bond forming Heck, Suzuki and Sonogashira coupling reactions, thus affording 2-deoxy-2-C-alkyl/aryl septanosides. Whereas Heck and Sonogashira coupling reactions afforded 2-deoxy-2-C-alkenyl and -alkynyl derivatives, respectively, the Suzuki reaction afforded 2-deoxy-2-C-aryl

• , Heck, Suzuki and Sonogashira coupling reactions. Heck coupling reactions [24][25] were undertaken first. Thus, the reaction of bromo-oxepine 2 with methyl acrylate was performed, in the presence of Pd(OAc)2 (10 mol %) and Cs2CO3 in 1,4-dioxane, at 98 °C (Scheme 1), to afford diene 3, in 70% yield. The

• substrate presenting two acrylates within the molecule, styrene, and α-methyl styrene (Scheme 1). Reactions with these substrates also afforded the diene products 4–7, in good yields. The anticipated two Heck coupling reactions with the substrate that presents two acrylates, could not be achieved, rather

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• the 2010 Nobel Prize in Chemistry to Heck, Negishi and Suzuki for their contributions to the development of these reactions. Despite their widespread utilization in organic chemistry, cross-coupling reactions have been used rarely for the preparation of furanyl-substituted tpy. The only known