Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• 9. Substituted alkyne derivatives 10a and 10b were synthesized according to the literature. The Sonogashira coupling reaction [25] of aryl iodides with terminal acetylene is an effective approach towards the synthesis of substituted arylalkynes. The reaction of 1-iodo-4-methoxybenzene and 1-iodo-4

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

• 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

• formation of a copper(I) complex from the 1,2-ketone and the hydroxy group, which further coupled with aryl iodides through oxidative addition to generate a copper(III) complex. Phenols were liberated by the following reductive elimination [29]. You and co-workers used the same copper catalyst and reported

• that a N,N-bidentate ligand, 2,2’-bipyridine (L5) could prompt the conversion of aryl halides to phenols in the presence of KOH as coupling partner (Scheme 8) [30]. Aryl iodides and electron-deficient aryl bromides were easily converted to the corresponding phenols in good to excellent yields. A broad

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• bile acids. High yields of arylaminocholanes were achieved in copper-catalyzed reactions of aryl iodides with 24-aminocholanes, while only a classical Pd-catalyzed protocol was suitable for the cross-coupling of aminocholanes and dichloroanthraquinones. The presence of hydroxy groups in the substrates

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• development of a new design of organocatalysts based on aryl iodides as halogen bond donors [73][82][83][84][85][86][87][88]. These catalysts were found to act as organic Ag+ surrogates and activate an ionizable substrate by halide anion scavenging. Thus, in 2011, Stefan M. Huber and his colleagues

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

• arylation to the C5-position (Scheme 1, middle) [35]. Mori et al. also reported two examples of C5-arylation of 2-bromo-3-methylthiophene with aryl iodides as aryl sources with 5 mol % PdCl2(PPh3)2 catalyst and AgNO3–KF as the base in DMSO (Scheme 1, bottom) [36]. Herein, we wish to report on green

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

• reactions reported using aryl iodides can be linked to the use of DMF as a solvent [5]. In this context, the sustainability movement within pharmaceutical research and development strives to substitute solvents that have regulatory and environmental issues for those with a lower perceived risk. Indeed

• reaction time, this was a substrate-specific problem for the use of 2a with these ortho-substituted aryl iodides that was not apparent for other alkyne/ortho-substituted iodoarene combinations (Scheme 2c). Judicious selection of reacting components also enabled the development of a useful Cacchi-type

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

• , phosphine additives and strong heating or microwave conditions in order to effect coupling with most acetylenes. Accordingly, it was anticipated that the aryl iodides would be more versatile due to their greater propensity to undergo oxidative additions. Therefore, in this paper we report herein the

Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

• William A. Nack,
• Xinmou Wang,
• Bo Wang,
• Gang He and
• Gong Chen

Beilstein J. Org. Chem. 2016, 12, 1243–1249, doi:10.3762/bjoc.12.119

• −H functionalization reactions starting from readily accessible aryl iodide and alkylamine precursors (Scheme 1) [8]. Alkylpicolinamides were first subjected to Pd-catalyzed γ-C(sp3)−H arylation with aryl iodides to form γ-arylpropylpicolinamides [9][10][11][12][13][14][15][16][17][18][19][20]. These

• examined the substrate scope of this Pd-catalyzed iodination of γ-arylpropylpicolinamides (Table 2). The γ-arylpropylpicolinamides were prepared from the corresponding N-alkylpicolinamides and aryl iodides under our (BnO)2PO2H-promoted Pd-catalyzed γ-C(sp3)−H arylation conditions (see Supporting

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. Keywords: 1,2-addition; aryl iodides; ketones; nucleophilic addition; palladium catalysis; Introduction For our systematic studies on samarium diiodide promoted cyclizations

• leading to benzannulated medium-sized rings [1][2][3][4] we required starting materials such as alkenyl-substituted compounds B (Scheme 1). Obvious precursors for B are aryl iodides A that smoothly undergo palladium-catalyzed coupling reactions to provide the desired products. However, in one case [A: R1

• this study [30]. Possible mechanisms for this process leading to the formation of an iminium intermediate or a dehydrogenation of the amine are depicted in Scheme 10. Conclusion We have found new examples of intramolecular palladium-catalyzed nucleophilic additions of aryl iodides to alkyl ketones

Synthesis of β-arylated alkylamides via Pd-catalyzed one-pot installation of a directing group and C(sp³)–H arylation

• Yunyun Liu,
• Yi Zhang,
• Xiaoji Cao and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2016, 12, 1122–1126, doi:10.3762/bjoc.12.108

• .12.108 Abstract The synthesis of β-arylated alkylamides via alkyl C–H bond arylation has been realized by means of direct one-pot reactions of acyl chlorides, aryl iodides and 8-aminoquinoline. Depending on the structure of the starting materials, both single and double β-arylated alkylamides could be

• reaction temperature indicated that 120 °C was the favorable temperature (entries 16 and 17, Table 1). Following the above optimization experiments, the scope of this one-pot approach in the synthesis of arylated amides was then examined by subjecting different aryl iodides and acyl chlorides. According to

• reactions with AQ and aryl iodides, the in situ generated propionamide intermedidates underwent selectively double β-C–H arylation to provide the corresponding 3,3-diarylamides 5 (Scheme 1). What’s more, when cyclohexylformic acid (2f) was subjected with AQ and aryl iodides, the C–H bonds at the two

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• arylureas at room temperature. A commercially available catalyst [Pd(MeCN)4](BF4)2 or a nitrile-free cationic palladium(II) complex generated in situ from the reaction of Pd(OAc)2 and HBF4, effectively catalyzes C–H activation/cross-coupling reactions between aryl iodides, arylboronic acids and acrylates

• C–H arylations of arylureas with aryl iodides and arylboronic acids Among the most conceptually attractive approaches to aromatic C–H activation is the efficient synthesis of biaryls through direct arylation reactions. The widespread availability of aryl iodides and arylboronic acids make them

• ](BF4)2 [184], was found to efficiently catalyze the reaction between arylureas and arylboronic acids. On the other hand, C–H arylations with aryl iodides catalyzed by [Pd(MeCN)4](BF4)2 did not give any of the desired products (see mechanistic discussion; vide infra). Various neutral palladium catalysts

Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates

• Michael Edmunds,
• Mohammed Abdul Raheem,
• Rebecca Boutin,
• Katrina Tait and
• William Tam

Beilstein J. Org. Chem. 2016, 12, 239–244, doi:10.3762/bjoc.12.25

• ring-opening reactions of C1 substituted 7-oxanorbornadiene derivatives with aryl iodides were investigated. The optimal conditions for this reaction were found to be PdCl2(PPh3)2, ZnCl2, Et3N and Zn in THF. Both steric and electronic factors played a role in the outcome of the reaction as increasing

• the steric bulk on the bridgehead carbon decreased the yield. These reactions were found to be highly regioselective, giving only one of the two possible regioisomers in all cases. A diverse collection of novel, highly substituted biphenyl derivatives were obtained. Keywords: aryl iodides

• ; oxabenzonorbornadiene; palladium catalysis; regioselectivity; ring-opening reactions; Introduction Palladium-catalyzed ring-opening reactions of 7-oxanorbornadiene with aryl iodides produce unsymmetrical, highly-substituted biphenyl derivatives making this reaction a very useful tool in organic synthesis [1][2][3][4

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• reaction for this programme involved the carbonylation of aryl iodides 5, 6 and 7 which are derived by HIO4 treatment of all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane (4). The ortho isomer 5 was separated from the meta and para isomers 6 and 7, the latter of which were recovered as a mixture as

• previously reported [8]. Palladium catalysed carboxylation [9] was explored with aryl iodides 5 or 6/7 as a mixture, and these gave the corresponding ethyl esters 8 and 9/10, respectively. The meta and para esters 9 and 10 were easily separated by chromatography. Hydrolysis of esters 8–10 using

• trifluoroacetic acid (TFA) or 6 M HCl in dioxane [10] gave the corresponding benzoic acids 11, 12, and 13 as illustrated in Scheme 1. Direct palladium catalysed formylation of aryl iodides 6/7 as a mixture was explored using Pd(PPh3)4, Bu4SnH and CO [11]. This generated benzaldehyde derivatives 14 and 15 in a 1:3

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

• the addition of silver salts is effective for the copper-mediated trifluoromethylation of aryl iodides [38] (Scheme 5). The amount of copper used in the reaction was reduced to 30 or 40 mol % by adding a small amount of Ag2O. As a related decarboxylative transformation, silver-mediated aromatic

• trifluoromethylation of aryl iodides with ClCF2CO2Me and fluoride can be utilized for clinical studies. Herein, we introduce one example of decarboxylative [18F]trifluoromethylation for positron emission tomography (PET) studies. A synthetic methodology for [18F]labelled-CF3 arenes is desired for the application of

• indicated that the CF3Cu reagent is directly formed from tetrahedral intermediate A [44] (Scheme 10). The CF3Cu reagent was applied to aromatic trifluoromethylation with aryl iodides, which have electron-withdrawing or electron-donating functional groups, in good to high yields (Scheme 11). The preparation

Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

• Bijay Shrestha and
• Ramesh Giri

Beilstein J. Org. Chem. 2015, 11, 2400–2407, doi:10.3762/bjoc.11.261

• added dropwise a solution of aryllithium (3.0 mmol, generated from the lithiation of aryl iodides with 1 equiv of n-BuLi in THF) at room temperature. After 45 minutes, the solvent was removed to obtain a triarylaluminum reagent containing 3 equivalents of LiCl, which was then dissolved in NMP (5 mL

Cu(I)-catalyzed N,N’-diarylation of natural diamines and polyamines with aryl iodides

• Svetlana P. Panchenko,
• Alexei D. Averin,
• Maksim V. Anokhin,
• Olga A. Maloshitskaya and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2015, 11, 2297–2305, doi:10.3762/bjoc.11.250

• polyamines such as putrescine, cadaverine, spermine, spermidine and their homologues is described. Aryl iodides bearing electron-donating and electron-withdrawing groups have been employed in the study. The CuI/2-(isobutyryl)cyclohexanone/DMF catalytic system has found to be more efficient in the diarylation

• of diamines and spermine while the CuI/L-proline/EtCN system proved to be preferable for the diarylation of other tri- and tetraamines like spermidine, norspermidine and norspermine. Keywords: amination; aryl amines; aryl iodides; copper catalysis; polyamines; Introduction Natural diamines and

• -aryldiamines using aryl iodides in the presence of CuCl under neat conditions [28], N,N’-diarylation of the simplest propane-1,3-diamine and butane-1,4-diamine was carried out using a CuI-metformin catalyst [29], monoarylation of mono- and diamines was studied using Cu2O and CuO nanoparticles and CuO

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• hydrodehalogenations of both electron-rich and electron-poor aryl iodides 51 took place in good yields (Scheme 12). Furthermore, unactivated aryl 53 and alkyl iodides 55 and 57 bearing unsaturated side chains underwent reductive 5- and 6-exo-cyclization reactions enabling several types of heterocycles (54, 56, and 58

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

• . Starting from aniline derivative 1b, a one pot diazotization–borylation sequence using different acids afforded the corresponding borylated product 2b in good yields (Table 3). Suzuki–Miyaura cross-coupling reactions of boronates 2a and 2b with aryl iodides using a simple system without any optimization

• electron-donor or acceptor groups while ortho-substituted substrates are less reactive. A mechanism involving aryl radicals is suggested. The Suzuki–Miyaura reaction of SF5-phenylboronates with aryl iodides provided the cross-coupling biaryl products. In analogy to the borylation reaction, iodination of

• aryldiazonium tetrafluoroborates with pyridine and iodine resulted in aryl iodides. An efficient reaction was observed with electron-acceptor substituted aromatic compounds even with ortho-substituted derivatives. In the case of SF5-substituted iodobenzenes, the method is much more efficient than the classical

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 formed aryl iodides by recourse to transition metal-catalyzed coupling reactions [37]. When bis-heterocyclic compound 1a was reacted in THF for 2 h at room temperature with the lithium–zinc base, in situ prepared from ZnCl2·TMEDA (0.5 equiv) and LiTMP (1.5 equiv), a selective deprotonation at the

• obtained together with recovered starting material. In order to test the functionalization of the above synthesized aryl iodides through a subsequent transition-metal-catalyzed coupling reaction we subjected three of them to a copper-catalyzed N-arylation reaction. Thus, the iodides 3b, 3d and 4d were

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• recognized (e.g., reductions, acidic medium, carbene addition, etc.). Because we would like to check the possibility of performing the Mizoroki–Heck cross-coupling reaction with nitroxides, herein the synthesis of cinnamates bearing a nitroxyl moiety is presented using aryl iodides as exemplary test

• may cause hindered interaction with substrates. Some of the catalytic sites may be buried within the polymer matrix and cannot participate in the reactions [46]. This disadvantage may cause various unwanted effects. As examples, no clear relationship between the structures of the aryl iodides and the

• yields were observed, as described in [47], or a catalyst that accepts only electron-rich aryl iodides [48]. The structure of the synthesized cinnamates bearing a nitroxyl moiety were confirmed using EIMS, ESIMS, HREIMS, HRESIMS, 1H NMR, 13C NMR, and IR spectra (Experimental part and Supporting

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

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• , such as copper and manganese salts, were less often employed for this purpose. 3.1 Oxidative systems based on iodine compounds Iodine(III) organic compounds, including those generated in situ from aryl iodides and peracids (for example, m-chloroperbenzoic acid (MCPBA) and peracetic acid) are most

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• reaction, we turned our attention towards the use of more reactive aryl iodides. A screen of solvents commonly used in Pd-catalyzed cross-coupling reactions revealed that DMF provided the highest yields (Table 1, entries 3–5). We next examined the effect of varying equivalents of the terminal reductant

• bipyridyl ligands that have been used to prepare strongly photooxidizing metal–polypyridyl complexes [32][33][34][35][36]. In each case, the requisite aryl iodides are either commercially available or can be easily synthesized by Finkelstein displacement of the aryl chloride with NaI [37]. Finally, we

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• aryl iodides as starting material and also requires a convenient imine derivative allowing the cleavage of the nitrogen-attached group (R5) at some point in the catalytic cycle (Scheme 13). It is noteworthy that polar solvents (DMF, N-methylpyrrolidone, and acetonitrile) had favourable impact on the