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

• , and 1,4-dioxane/H2O as solvent (Scheme 1). Under these conditions, a wide range of aryl bromides and chlorides could be readily converted to the corresponding phenols in high yields at 100 °C within 1–18 h. Moreover, sterically hindered ortho-functionalized aryl halides and heteroaryl halides were

• poorer efficiency of copper catalysts than that of palladium catalysts often limits the substrate scope to aryl iodides and aryl bromides. In 2009, two independent works by Taillerfer and You opened the prelude to the copper-catalyzed hydroxylation of aryl halides. The Taillefer group found that a

• -3-oxobutanamide (yield 65%), tetramethylethylenediamine (TMEDA, yield 84%), phenanthroline (yield 75%), 2,2,6,6-tetramethyl-3,5-heptanedione (TMHD, yield 95%) and dibenzoylmethane (L4, yield 97%) [27][28]. The reaction system afforded phenols from aryl halides and aryl bromides bearing electron

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides

• Yi Lai,
• Zhijian Zong,
• Yujie Tang,
• Weimin Mo,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen,
• Liqun Jin,
• Wen-hua Sun and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 213–221, doi:10.3762/bjoc.13.24

• showed a good catalytic efficiency for both Suzuki and Heck cross-coupling reactions. The favorable effect originated from the ring-fused framework being able to establish a strained environment for better stability. Efficient couplings were achieved with aryl bromides or iodides as substrates, however

• without any change except at the higher reaction temperature. As shown in Table 1, using complex Pd1, which has exhibited an impressive efficiency in Pd-catalyzed Suzuki coupling of aryl bromides, only delivered 18% conversion of chlorobenzene. The modification of the Cb position by importing two methyl

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

• introduction of aryl substituents at C5-position via Pd-catalysed direct arylation. With 1 mol % of a phosphine-free Pd catalyst, KOAc as the base and DMA as the solvent and various electron-deficient aryl bromides as aryl sources, C5-(hetero)arylated thiophenes were synthesized in moderate to high yields

• “green” access to arylated thiophene derivatives as it reduces the number of steps to prepare these compounds and also the formation of wastes. Keywords: aryl bromides; C–H bond activation; catalysis; direct arylation; palladium; thiophenes; Introduction Thiophene derivatives bearing aryl substituents

• regiospecific access to C5-arylated 2-bromothiophenes without cleavage of the thienyl C–Br bond, ii) on the reaction scope using a set of aryl bromides and 2-bromo-3-substituted thiophenes, iii) conditions allowing either the sequential C5-arylation followed by C2-arylation or C2-heteroarylation followed by C5

Scope and limitations of a DMF bio-alternative within Sonogashira cross-coupling and Cacchi-type annulation

• Kirsty L. Wilson,
• Alan R. Kennedy,
• Jane Murray,
• Ben Greatrex,
• Craig Jamieson and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2016, 12, 2005–2011, doi:10.3762/bjoc.12.187

• functionalised aryl and heteroaryl iodides were tolerated (Scheme 2a). In addition, electron-deficient aryl bromides were accommodated, although with some variation in yield (3c, 3l, 3o, 3n). Functionality on the alkyne component was also typically well tolerated (Scheme 2b). While 3i and 3j required an extended

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• elimination pathway, with the expelled DIBAL-derived aluminate likely functioning as the base. With optimised syntheses of 21 and 22 in hand, the reactivity of their iodo substituents towards cross-coupling reactions was compared to that of the corresponding aryl bromides. Table 3 shows an example where 21

• was to synthesise THQs and DHQs of the general scaffold 1 for the use in a variety of cross-coupling reactions, thus necessitating the presence of a halogen or pseudohalogen in the para-position relative to nitrogen. Most of the relevant literature focuses on the synthesis of the corresponding aryl

• bromides or aryl chlorides, but initial investigation with 6-bromo-THQs indicated that these were remarkably unreactive in cross-coupling reactions [14], and a reliable and scalable synthesis of the likely more reactive iodides was, therefore, sought. We first considered the retrosynthetic analysis shown

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• of the C2F5Cu reagent was investigated as well [45]. Pentafluoropropionate was reacted with CuCl salt in the presence of KOt-Bu to afford C2F5Cu. A variety of aryl bromides were reacted with C2F5Cu under the optimized conditions, providing pentafluoroethylated aryl products in moderate to high yield

• trifluoroacetate and copper iodide. Preparation of trifluoromethylcopper from trifluoromethyl ketone. Trifluoromethylation of aryl iodides. aIsolated yield. b1 equivalent each of CF3Cu reagent and 1,10-phenanthroline were used. cReaction temperature was 50 °C. Pentafluoroethylation of aryl bromides. aYield was

Half-sandwich nickel(II) complexes bearing 1,3-di(cycloalkyl)imidazol-2-ylidene ligands

• Johnathon Yau,
• Kaarel E. Hunt,
• Laura McDougall,
• Alan R. Kennedy and
• David J. Nelson

Beilstein J. Org. Chem. 2015, 11, 2171–2178, doi:10.3762/bjoc.11.235

• . The new species were fully characterised using methods including NMR spectroscopy and X-ray crystallography. When tested in model Suzuki–Miyaura cross-coupling reactions, these complexes were found to be active for the cross-coupling of aryl bromides and aryl chlorides. Keywords: catalysis; cross

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

• . Palladium-catalyzed desulfitative arylation of heteroarenes allowed in a first step the synthesis of fluoroaryl-heteroarene units in high yields. Then, the next steps involve direct arylation with aryl bromides catalyzed by PdCl(C3H5)(dppb) to afford triad or tetrad heteroaromatic compounds via

• involved in palladium-catalyzed direct arylations with a set of heteroarenes (e.g., thiophenes, thiazoles, furans). Then, the resulting heteroarylated polyfluorobenzenes were arylated using PdCl(C3H5)(dppb) catalyst in the presence of KOAc as the base in DMA at 150 °C using a wide range of aryl bromides as

• arylated in β-position instead of α-position with the classical procedure employing aryl halides as coupling partners [53][55] and benzofuran regioselectively led to C2 arylated compounds instead of the mixtures of C2 and C3 arylated products obtained with aryl bromides [56]. Moreover, these processes are

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

• C–H borylation of several 1-substituted-3-(pentafluorosulfanyl)benzenes and applied the products of borylation to the Pd-catalyzed Suzuki–Miyaura reaction with aryl bromides or iodides. However, the reaction is limited to borylations in position five of 1-substituted-3-(pentafluorosulfanyl)benzenes

• potassium SF5-phenyltrifluoroborates were found to be highly reactive with a variety of aryl bromides and iodides in the presence of catalytic amounts of PdCl2(dppf)·CH2Cl2 or Pd(OAc)2 [72]. The recently published synthesis of arylboronic acids from anilines or aryldiazonium tetrafluoroborates using B2(OH)4

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• carbonate as the base, in acetonitrile at reflux [44] (Table 1, Figure 2, Supporting Information File 2). Varying yields were obtained, with aryl iodides substituted by electron-withdrawing groups in general favouring the reaction. In contrast, much lower yields were noted when using aryl bromides. For the

• the synthesis of the N-arylated pyrroles and indoles 1a,b,d,e and 2a–e [44]. To azole (6.0 mmol) and aryl halide (4.0 mmol) in acetonitrile (20 mL) were successively added Cu (50 mg, 0.80 mmol), Cs2CO3 (2.6 g, 8.0 mmol) and, in the case of aryl bromides, KI (99 mg, 6.0 mmol). The mixture was stirred

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• 4m–w. Acceptable yields can be obtained with both aryl bromides and aryl iodides, suggesting that the choice of halogen is not critical. N-Arylation of dimethylated MPTTF 4g’ gave the lowest yield amongst the reactions performed under sealed tube conditions, which may be attributable to its more

Weakly nucleophilic potassium aryltrifluoroborates in palladium-catalyzed Suzuki–Miyaura reactions: relative reactivity of K[4-RC₆F₄BF₃] and the role of silver-assistance in acceleration of transmetallation

• Vadim V. Bardin,
• Anton Yu. Shabalin and
• Nicolay Yu. Adonin

Beilstein J. Org. Chem. 2015, 11, 608–616, doi:10.3762/bjoc.11.68

• continuation of systematic research of the Suzuki–Miyaura cross-coupling reaction of weakly nucleophilic organotrifluoroborates we report here the study of the relative reactivity of K[4-RC6F4BF3] in the Pd-catalyzed reactions with some aryl bromides and iodides in the presence of Ag2O. The borates were chosen

• , entries 2–14) while 4-CH3C6H4C6F5 (10a) was isolated in 93% yield (see Table 2, entry 1) [19]. Although aryl bromides are less reactive than iodides, the substitution of 4-IC6H4CH3 (9) for 4-BrC6H4CH3 (11) does not affect the yields of the corresponding biphenyls (Scheme 4). The obtained results show a

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• –lactonization cascade reaction using diethylzinc as a reductant [9]. Floch et al. have reported a catalytic synthesis of the γ-lactones from aryl bromides, zinc, dimethyl itaconate and aldehydes/ketones [10][11], which is characteristic in its simplicity, conciseness and high yielding, however with low

A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki–Miyaura cross-coupling reactions of aryl halides

• Claudia A. Contreras-Celedón,
• Darío Mendoza-Rayo,
• José A. Rincón-Medina and
• Luis Chacón-García

Beilstein J. Org. Chem. 2014, 10, 2821–2826, doi:10.3762/bjoc.10.299

• produce the desired biphenyl compounds in high to excellent yields (91–99%) (Scheme 2, compounds 3a–3h). The 16 reactions with aryl bromides 2c–2f also proceeded well and afforded the corresponding biphenyl products (Scheme 2 compounds 3i–3x) in moderate to high yields (61–98%). The catalytic system was

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

• -catalysed Mizoroki–Heck coupling reactions between aryl bromides and styrene on one hand, and the rhodium-catalysed asymmetric hydroformylation of styrene on the other hand. The inability of both chiral ligands to form standard bis(phosphine) complexes under catalytic conditions was established by high

• styrene and aryl bromides using [Pd(OAc)2] (OAc = acetate) as a palladium source [65]. In a preliminary study, 4-bromoanisole was reacted for 1 h with styrene in N,N-dimethylformamide (DMF) in the presence of Cs2CO3 (Table 3). The runs were carried out at different temperatures and L:M ratios. The highest

• results suggest that in the presence of an excess palladium, WIDEPHOS operates as a ligand with two independent monophosphine arms, each of them binding a palladium atom. We then applied the aforementioned optimal conditions in the coupling of styrene with different aryl bromides (Table 4), using either

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

• different aryl units. Keywords: aryl bromides; atom economy; C–H bond activation; palladium; regioselectivity; thiophenes; Introduction As thiophenes bearing aryl substituents are known to be present in several bioactive molecules and are used as precursors of materials, the regioselective introduction of

• thiophenes without the use of a blocking group at carbon C2. To our knowledge, ortho-substituents on aryl bromides have not been employed as directing groups for palladium-catalysed direct arylation of 3-substituted thiophenes. The use of congested aryl bromides for such couplings would certainly modify the

• regioselectivity in favour of arylation at the less hindered thiophene position. Herein, we wish to report on the influence of such ortho-substituents on aryl bromides on the regioselectivity of the palladium-catalysed direct arylations of 3-substituted thiophenes. Results and Discussion We first studied the

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• derived from diethyl 2-fluoromalonate ester as the first stage in the synthesis of fluoroacetic acid and fluoroxindole systems. While related palladium catalysed coupling processes between aryl bromides and diethyl 2-fluoromalonate have been described [51], reactions involving nucleophilic aromatic

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

• absorption and fluorescence characteristics. Here we describe the first palladium-catalysed Suzuki–Miyaura cross-coupling reaction of easily accessible and ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole derivatives with various aryl bromides. Aryl bromides bearing electron-withdrawing

• palladium-catalyzed cross-coupling reaction of 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds with aryl bromides in only 10 minutes. Results and Discussion As shown in Scheme 1, 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds were easily prepared from aryl halides 7 via the reaction of

• compounds that can participate effectively as coupling partners in the cross-coupling reaction is still necessary. We have synthesised a range of 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds and developed their first Pd-catalysed Suzuki–Miyaura cross-coupling reaction with a range of aryl

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

• several authors for the phosphination of a large variety of compounds [180][181][182][183][184][185][186][187][188]. Microwave-assisted procedures have also been developed [189][190][191]. Kwong et al. implemented a palladium-catalyzed phosphination of aryl bromides and triflates 104 with

• substrates compared to aryl triflates. Zhao and co-workers disclosed a method for the cross coupling of various aryl bromides 119 with diphenylphosphine (25d) in the absence of external reductants and supporting ligands [219]. The reaction gave mixtures of phosphines 120 and phosphine oxides 121 (Scheme 34

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

• Unsymmetrically coupled biaryls are synthesized in high yield starting from different aryl bromides and bis(pinacolato)diboron by carrying out the Miyaura borylation reaction followed by the Suzuki–Miyaura reaction in the same reaction pot over 1–2 mol % SiliaCat DPP-Pd. The SiliaCat DPP-Pd catalyst is air-stable

• shown elsewhere [10], wherein the issue of catalyst recycling is also addressed in detail. Now we report a new method that establishes a direct route, in one-pot, to unsymmetrically coupled biaryls starting from two different aryl bromides and bis(pinacolato)diboron without the need to isolate the

• –Miyaura reaction. Results in Table 1 show that, following aqueous work-up, different unsymmetrically coupled compounds are obtained in good to excellent yields by coupling numerous different aryl bromides with different aryl halides, including heteroatom-containing aryls. In detail, entries 1 and 2 in

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• [23][36]. This versatile intermediate 59 was reacted with aldehydes, imines, olefins and aryl bromides or aryl iodides to generate a wide range of phosphinates. The same authors have also prepared another H-phosphinate intermediate 61 in 71% yield (Scheme 25) [37]. This oxazaphosphinane 61 was

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• be achieved by benzylic positioning as well as by choosing aryl bromides A (Scheme 3) that can be modified to the corresponding aryl alkynes C by cross coupling chemistry. Previously, we successfully utilized this combination of mutasynthesis and semisynthesis for 19-brominated ansamitocin

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

• -36075 Vicenza, Italy 10.3762/bjoc.10.36 Abstract Two efficient protocols for the palladium-catalyzed synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides in the absence of copper were developed. A simple catalytic system consisting of Pd(OAc)2 and P(p-tol)3 using DBU as the base and THF as the

• solvent was found to be highly effective for the coupling reaction of 2-methyl-3-butyn-2-ol (4) with a wide range of aryl bromides in good to excellent yields. Analogously, the synthesis of aryl-2-methyl-3-butyn-2-ols was performed also through the decarboxylative coupling reaction of 4-hydroxy-4-methyl-2

• -pentynoic acid with aryl bromides, using a catalyst containing Pd(OAc)2 in combination with SPhos or XPhos in the presence of tetra-n-butylammonium fluoride (TBAF) as the base and THF as the solvent. Therefore, new efficient approaches to the synthesis of terminal acetylenes from widely available aryl

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

• -reducing side-reactions to consume the aryllithium reagents 34a,b to some extent, as delineated below. Therefore, acid 10 was treated with an excess of 34a,b which were generated from aryl bromides, using either 2.5 equivalents thereof together with tert-butyllithium (t-BuLi, five equiv) or four

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

• trifluoromethylated arenes in good yields, and a variety of functional groups is tolerated under the mild conditions of the process. The reaction with aryl bromides or triflates is less efficient. The success of this Pd-catalyzed trifluoromethylation is due to highly hindered phosphorus ligands like BrettPhos, which

• effective reaction site for oxidative addition of Ar–X and the Pd(0) catalyst, increasing the yields and allowing the use of aryl bromides as starting materials (Table 3). Free alcohols and amines are compatible with the reaction conditions, which was not the case with S. L. Buchwald’s methodology. For the

• trifluoroacetate (MTFA) and cesium fluoride to generate the trifluoroacetate anion which decarboxylated under the reaction conditions (Figure 5). In most cases, the system does not necessitate the use of amine ligands excepted when aryl bromides are used instead of aryl iodides [81]. Aryl and heteroaryl products