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

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• prepared p-bromophenyl-substituted bicyclic 1,2-oxazine derivatives 12, 13, 15 and 16 provide options to perform cross-coupling reactions such as Buchwald/Hartwig, Heck, Hiyama, Kumada, Sonogashira or Stille couplings. In order to examine the conditions for Suzuki cross-couplings we subjected bicyclic

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

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• mechanistic pathways. Our experiments (Scheme 6) afforded quantum yields of Φ > 1 for the heterobiaryl coupling [15] and the Heck-type olefination with styrene [16], respectively. This indicates that in addition to a photocatalytic path (Scheme 2, A) radical-chain propagation is operating under the reaction

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

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• (Heck-type cyclization), unfortunately, were unsuccessful. Heck-type cyclizations work nicely with planar PAHs and even on moderately curved PAHs, such as corannulene [15][23][24]. Nonetheless, when applied to the indenocircumtrindene synthesis, the reaction did not give any ring-closed products

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