Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• [37], reactions were performed in EtOH/H2O 7:3 (v/v) at 75 °C using K2CO3 as inorganic base. Phenylboronic acid as well as K2CO3 were added in 50% molar excess relative to the corresponding aryl bromide, whereas a catalyst amount corresponding to 0.05 mol % of Pd was used. The reaction progress was

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

• %), imidazolium salts L1–L3 (1% aqueous solution, 0.05–0.1 mol %), NaOEt (2.0 mmol) and 1.5 mL water were successively added, followed by preheating at 60 °C for 30 min. Then, aryl bromide (1.0 mmol) and styrene (1.2 mmol) were added, purged with N2, sealed and heated at 100 °C. After 12 h, the solution was

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

• interested in investigating the synthetic applicability of this catalyst in a natural product synthesis. For this purpose, the reaction between aryl bromide 1d and 4-acetoxystyrene (2d) was studied to obtain (E)-pterostilbene (19, Scheme 1). Several derivatives of polyphenolic stilbenes as (E)-pterostilbene

• are natural products, which present an interesting biological activity [59]. Under the above mentioned reaction conditions (E)-pterostilbene (19) was obtained in moderate yield, but with a high TOF value considering the use of deactivated aryl bromide 1d. Additionally, cleavage of the acetyl group in

• -diphenylvinyl)phenyl)ethanone (15) [56], and (E)-4-(3,5-dimethoxystyryl)phenol or pterostilbene (19) [60]. Representative procedure for the MW-assisted Stille–Heck coupling reactions Analogously to the procedure described in [47], into a 10 mL MW tube equipped with a magnetic stirring bar, aryl bromide 1a, 1d

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

• substrates are well tolerated to give the corresponding coupling products smoothly with yields of 60–80%. Finally, the coupling reactions of aryl bromide 1i and styrene (2a) as well as heterocyclic bromide 1m and styrene (2a) were chosen as the model reactions under the optimized conditions to investigate

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• Scheme 2. A Weinreb amide (1 equiv) and PhMgBr (2 equiv, Grignard’s reagent) are reacted in a 10 mL PFA coil at 60 °C for 5 min residence time. The reaction is quenched using aq HCl and the ketone is isolated with 97% yield. The aryl lithium compound is produced simultaneously by reacting aryl bromide (1

• the conversion can be monitored online to check the variation around the set-point value. This process stream containing the ketone intermediate can be precooled to −50 °C. Aryl bromide and n-BuLi are precooled at −50 °C and reacted to obtain the lithiated product. The control strategy for lithiation

• the multistep synthesis of rufinamide, an antiepileptic agent [14] (Scheme 3). The process involves three steps namely azide synthesis, amide synthesis and click reaction or azide–alkyne cycloaddition. For the azide synthesis, the aryl bromide (1 equiv) and sodium azide (1.3 equiv) are reacted in a

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• /PANI catalyzed a Suzuki coupling reaction and hydroxylation of aryl halides [25]. The hydroxylation of aryl halides occurred at 100 °C in aqueous 1,4-dioxane in the presence of 1 mol % of Pd/PANI and 4 equiv of KOH (Scheme 5). Aryl bromide and iodides were converted to the corresponding phenols in good

• –80 °C, affording the phenols from aryl iodides and bromides in good to excellent yields (Scheme 23). In the case of aryl bromide, long reaction time (48 h) was required. 110 mol % of CuI-nanoparticles was needed for the complete conversion of aryl bromides bearing electron-donating groups. It's worth

• with TBAF. In 2011, the Fu and Guo group reported that Pd(OAc)2/X-Phos (L16) and Pd2(dba)3/X-Phos-catalyzed thiolation of aryl bromide and chloride using sodium thiosulfate as thiol source [101]. The coupling reaction proceeded in water in the presence of Cs2CO3, and first gave aryl thiosulfate, which

Chromium(II)-catalyzed enantioselective arylation of ketones

• Gang Wang,
• Shutao Sun,
• Ying Mao,
• Zhiyu Xie and
• Lei Liu

Beilstein J. Org. Chem. 2016, 12, 2771–2775, doi:10.3762/bjoc.12.275

• -dimethoxyethane (DME) was identified to be the best choice (Table 1, entries 8–10). Lowering the reaction temperature was found to be beneficial for improving the enantioselectivity, and when the reaction was performed at −20 °C, expected 2a was isolated in 81% yield with 97% ee (Table 1, entries 10–13). Aryl

• bromide proved to be an inferior coupling component, providing 2a in 35% yield and 70% ee (Table 1, entry 14). With the optimized conditions in hand, the scope of the ketone component was first explored (Scheme 1). Aliphatic ketones with (longer) alkyl chain such as ethyl (1b) and n-hexyl ketones (1c

Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

• Mariem Brahim,
• Hamed Ben Ammar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2016, 12, 2197–2203, doi:10.3762/bjoc.12.210

• expected coupling products 2–4 were obtained in moderate yields. On the other hand, with 4-bromoanisole as an electron-rich aryl bromide, the desired C5-arylated 2-bromothiophene could not be detected by GC–MS analysis of the crude mixture, and a large amount of unreacted 4-bromoanisole was recovered

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• known facile coupling nature of aryl bromide [42] and its presence as part of the substrate, we obtained high regio-selective couplings with polyhalogenated benzofurans. The corresponding coupling products 2.22–2.27 were obtained in high yields (Table 2, entries 22–27). It is to be mentioned at this

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• optimal, providing the product with excellent enantioselectivity (Scheme 18c). Notably, the authors did not observe any side reaction between the palladium and aryl bromide or aryl iodide groups. Using NMR analysis and ESIMS Sodeoka and co-workers probed the mechanism of the reaction, observing a complex

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

• [46][59][60] and C3-arylation of furans [61][62] (i.e., 2 mol % PdCl(C3H5)(dppb) as catalyst associated to KOAc as base in DMA). We were pleased to find that 2-butyl-5-(2,3,4-trifluorophenyl)furan (1) was preferentially arylated on the electron-deficient ring whichever the aryl bromide was. For

• , compound 13, was isolated in 35% yield. This lower yield might be explained by a slower oxidative addition rate to the palladium with this electron-rich aryl bromide. Next, we investigated the reactivity of 1-methyl-2-(2,3,4-trifluorophenyl)pyrrole (4) in a second direct arylation (Scheme 3). Using of PdCl

• -(difluorophenyl)heteroarenes 19–24 in hands, we studied their reactivity in Pd-catalyzed direct arylations using PdCl(C3H5)(dppb) as catalyst in the presence of KOAc as the base and aryl bromide as coupling partners (Scheme 6). On 2-(3,4-difluorophenyl)menthofuran (23), the two C–H bonds at ortho-position to a

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• literature describes the synthesis of 3- or 4-(pentafluorosulfanyl)phenylboronates or boronic acids from SF5-bromobenzenes via lithiation or magnesiation. These approaches suffer from low yields and other drawbacks [70][71]. For lithiation of the aryl bromide, t-BuLi had to be used and the formation of

• Grignard reagents is inefficient. On the other hand, Shibata and co-workers have recently reported the synthesis of 3,5-bis(pentafluorosulfanyl)phenylboronic acid from the corresponding aryl bromide, trimethyl borate and iPrMgBr [32]. Finally, Joliton and Carreira have recently shown efficient Ir-catalyzed

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• substrates 7 we started from commercially available (+)-pulegone (4) in technical grade (92%) (see Scheme 5). First, the desired aryl moiety was installed by cuprate addition generated from aryl bromide 5, yielding the corresponding menthones 6a–c in good yields. In all cases, simple distillation is

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

• + Na]+. General procedure for palladium-catalysed Heck cross-coupling reactions: In an oven-dried Schlenk tube, a solution of [Pd(OAc)2] in DMF, a solution of HUGPHOS-1/2 or WIDEPHOS ligands in DMF, aryl bromide (1 equiv), styrene (2 equiv), Cs2CO3 (2 equiv), decane (internal reference) and additional

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• use of the congested aryl bromide 2-bromo-1,3-dichlorobenzene as coupling partner allows to modify the regioselectivity of the arylation of 3-substituted thiophene derivatives in favour of carbon C5. The coupling of this aryl bromide with a variety of 3-substituted thiophenes gave in all cases the

• )2 as the catalyst. However, under these conditions, a poor regioselectivity was observed as the desired C5-arylation product 1b was only obtained in 34% selectivity together with 66% of C2-arylation product 1a. Moreover, a moderate conversion of this aryl bromide was observed and purification by

• GC–MS analysis of the crude mixture. Moreover a high conversion of 86% of this aryl bromide was observed using only 0.5 mol % Pd(OAc)2 as the catalyst. Then, we studied the scope of the coupling of 2-bromo-1,3-dichlorobenzene, using other 3-substituted thiophene derivatives (Scheme 3, Table 1). Both

Palladium-catalysed cross-coupling reaction of ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds with aryl bromides: A direct protocol for the preparation of unsymmetrical biaryls

• Siphamandla Sithebe and
• Ross S. Robinson

Beilstein J. Org. Chem. 2014, 10, 1107–1113, doi:10.3762/bjoc.10.109

• , electron-neutral and electron-donating substituents are reacted under the catalytic system furnishing unsymmetrical biaryl products in isolated yields of up to 96% in only 10 minutes. Keywords: aryl bromide; 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole; asymmetrical biaryls; microwave; Suzuki–Miyaura

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• , the phosphines were protected as the corresponding borane adducts 65. The methodology is also applicable for aryl bromide 66 (Scheme 17) [23][24]. Alkenylphosphines were also synthesized by reacting alkenylzirconocenes 69 with a chlorophosphine 22b. Alkenylzirconocene compounds 69 displaying different

Clean and fast cross-coupling of aryl halides in one-pot

• Valerica Pandarus,
• Geneviève Gingras,
• François Béland,
• Rosaria Ciriminna and
• Mario Pagliaro

Beilstein J. Org. Chem. 2014, 10, 897–901, doi:10.3762/bjoc.10.87

• intermediate boronic acid pinacol ester. The overall process is described by Scheme 2. The SiliaCat DPP-Pd catalyst mediates the borylation and the subsequent Suzuki–Miyaura reaction in an elegant one-pot sequential synthesis. Hence, an aryl bromide is first converted into the boronic acid pinacol ester (step

• 1 in Scheme 2). A different aryl bromide is then added along with aqueous base (step 2). The reaction is carried out in iPrOH or in 2-BuOH. No work-up is performed after the borylation in the first step, nor is any catalyst added prior to conducting the second step of the sequence, the Suzuki

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• , sterically crowded and heterocyclic derivatives. Moreover, the coupling reaction seems to be very efficient and selective with regard to different functional groups placed on the aryl bromide, including acetamido, dimethylamino, methoxy, chloro, fluoro, trifluoromethyl, nitro, methoxycarbonyl and cyano

• derived from the starting aryl bromides in a 2–5% yield range. Likely, the acetone protecting group is cleaved from protected terminal alkyne even under such mild conditions and therefore, the terminal alkyne generated in situ couples with another molecule of the starting aryl bromide to provide the

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• equivalents of both aryl bromide and n-BuLi. The preformed sodium carboxylate of 10 in place of 36 was apparently too insoluble in Et2O to react with 34. The primary products 35 tend to eliminate Li2O slowly with formation of ketones 38 in the presence of aryllithium reagents 34 which will rapidly add to 38

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• the reaction of commercially available 2-methyl-1-propenylmagnesium bromide with 2-bromobenzyl bromide in the presence of CuI and 2,2’-bipyridyl [32]. This aryl bromide could be coupled with selected terminal alkynes by using cesium carbonate as a base and PdCl2(MeCN)2/XPhos as a catalytic system [33

An easy direct arylation of 5-pyrazolones

• Hao Gong,
• Yiwen Yang,
• Zechao Wang and
• Chunxiang Kuang

Beilstein J. Org. Chem. 2013, 9, 2033–2039, doi:10.3762/bjoc.9.240

• relatively low yields (Table 2, entries 3, 6–8). Entries 1 and 2 show that the yield of products was lower when using aryl bromide than when using aryl iodide, and 2-bromopyridine also provided 3i in moderate yield (Table 2, entry 10). Next, we investigated the scope of 5-pyrazolone 1 substrates. Table 3

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

• subjected to cross-coupling to produce the corresponding 1,2-disubstituted olefins. The results are summarized in Table 2. Both aryl bromide and aryl iodide performed well (Table 2, entries 1 and 2) under these conditions. However, the aryl chloride was found to be less reactive giving the corresponding

Controlled synthesis of poly(3-hexylthiophene) in continuous flow

• Helga Seyler,
• Jegadesan Subbiah,
• David J. Jones,
• Andrew B. Holmes and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2013, 9, 1492–1500, doi:10.3762/bjoc.9.170

• affect the polymerization in batch reactions despite the possibility that the aryl chloride solvent might participate in the Kumada reaction. Apparently, the reactivity of aryl chloride is significantly lower than that of aryl bromide under these reaction conditions. With the catalytic activity of Ni

Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

• Torsten Dittrich,
• Nils Hanekop,
• Nacera Infed,
• Lutz Schmitt and
• Manfred Braun

Beilstein J. Org. Chem. 2012, 8, 1700–1704, doi:10.3762/bjoc.8.193

• -4-arylaminopiperidines 17 and 18 A 25 mL two-necked flask, equipped with a magnetic stirrer and a connection to a combined argon/vacuum line was charged with piperidine 19 or 20 (3.6 mmol), the corresponding aryl bromide (3.6 mmol), sodium tert-butoxide (0.43 g, 4.5 mmol) and palladium acetate (10.1