Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• site-selective intramolecular iodoarylation by the appropriate cationic iodine species. Iodoarylation of 2-(2-aryl-3,3-difluoroallyl)biaryls proceeded via regioselective carbon–carbon bond formation at the carbon atoms in β-position to the fluorine substituents, thereby constructing dibenzo-fused six

• -membered carbocycles bearing a difluoroiodomethyl group. In contrast, 2-(3,3-difluoroallyl)biaryls underwent a similar cyclization at the α-carbon atoms to afford ring-difluorinated seven-membered carbocycles. Keywords: alkenes; carbocycles; cyclization; electrophilic activation; fluorine; iodine

• . Among the 1,1-difluoro-1-alkenes examined, 2-(2-aryl-3,3-difluoroallyl)biaryls underwent cyclization at the carbon atoms in β-position to the fluorine substituents to construct six-membered carbocycles bearing a difluoroiodomethyl group (Scheme 1a). On the other hand the cyclization of 2-(3,3

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• of their low reactivity. Recently, Li and Su with co-workers have developed a liquid-assisted grinding (LAG) method for the Suzuki–Miyaura coupling between aryl chlorides and boronic acids to synthesize the biaryls in nearly quantitative yield. Under optimized conditions 2 mol % Pd(OAc)2 and 4 mol

• % of PCy3·HBF4 along with an excess K2CO3–MeOH led to biaryls within 99 min and with a yield up to 97% (Scheme 8) [57]. Heck reaction Frejd and co-workers reported the first mechanochemical Heck reaction [58]. Su and co-workers demonstrated that (E)-stilbene derivatives were synthesized by the coupling

• palladium-catalyzed site selective mechanochemical dehydrogenative C–H/C–H arylation between oxime and arene moiety for the construction of Csp2–Csp2 bond with high para-selectivity of arene component via LAG. Using 10 mol % of Pd(OAc)2, 2.0 equiv of Na2S2O8 and 1.0 equiv TfOH the biaryls were synthesized

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• have recently demonstrated that bifunctional organocatalysts can also be applied to the asymmetric synthesis of axially chiral compounds (biaryls bearing isoquinoline N-oxides or quinolines and phenolic moieties) by translating a specific conformation, recognized by bifunctional organocatalysts, into

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• polyfunctionalized biaryls, using a flow microreactor, has been recently reported by Yoshida [54]. Using the integrated microflow system reported in Scheme 8, arylboronic esters were prepared by a lithiation/borylation sequence, and used in a Suzuki–Miyaura coupling in a monolithic reactor. A remarkable aspect of

• . Trifluoromethylation by continuous-flow photoredox catalysis. Flow photochemical synthesis of 6(5H)-phenanthridiones from 2-chlorobenzamides. Synthesis of biaryls 14a–g under photochemical flow conditions. Flow oxidation of hydrazones to diazo compounds. Synthetic use of flow-generated diazo compounds. Ley’s flow

One-pot synthesis of 4′-alkyl-4-cyanobiaryls on the basis of the terephthalonitrile dianion and neutral aromatic nitrile cross-coupling

• Roman Yu. Peshkov,
• Elena V. Panteleeva,
• Wang Chunyan,
• Evgeny V. Tretyakov and
• Vitalij D. Shteingarts

Beilstein J. Org. Chem. 2016, 12, 1577–1584, doi:10.3762/bjoc.12.153

• approach to a large number of functionalized biaryls with good or excellent yields. Nevertheless, the methodology has some disadvantages: the catalytic systems are quite expensive, the ligands are often hardly accessible and require special synthetic efforts, and preactivation of the substrates via

Stereodynamic tetrahydrobiisoindole “NU-BIPHEP(O)”s: functionalization, rotational barriers and non-covalent interactions

• Golo Storch,
• Sebastian Pallmann,
• Frank Rominger and
• Oliver Trapp

Beilstein J. Org. Chem. 2016, 12, 1453–1458, doi:10.3762/bjoc.12.141

• preparation of “NU-BIPHEPs” [23] and related biaryls [24]. Doherty et al. reported the use of various diynes yielding for instance tetrahydrobiindene 1a and N-tosyl-protected tetrahydrobiisoindole 1b as the only N-heterocyclic compound (Figure 1A). Aiming at facile deprotection and enabling subsequent

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

• 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

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• antihistamines for allergy treatment [10][11][12][13]. Other examples of pharmaceuticals containing a simple pyridine ring are rabeprazole [14][15], pentoprazole [16][17] and lansoprazole [18], which represent the well-known class of proton pump inhibitors. Furthermore, atropisomeric biaryls with a pyridine ring

• with increased reaction time to complete the diarylation. The attachment of small substituents at ortho positions in arylboronic acids did not retard the reaction (products 5, 8, 10, 18, 22, 24, 25, 29). However, the GC–MS analysis revealed an increased formation of the corresponding biaryls, monoaryl

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• coupling The biaryl motif is a key subunit in many natural products and axially chiral ligands. The classical Ullmann coupling is one of the most important methods for the practical synthesis of biaryls [14]. However, only few reports of an asymmetric version of the Ullmann coupling have been documented

• . The first attempt of an intermolecular asymmetric Ullmann coupling for the formation of biaryls was reported by Miyano and co-workers in 1980. The authors used a chiral ester group as auxiliary but only poor diastereoselectivity (13% de) was obtained [15]. A few years later, the same group took

• ] developed an efficient method for the synthesis of Isokotanin A (Scheme 9) and Tanaka et al. [29] also used this method for the synthesis of dimethylthiaheterohelicenes, which are highly hindered C2-symmetrical biaryls (Scheme 10). In 1994, an impressive progress was made by Lipshutz [30] in the

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• biaryls (products 1 and 7), whereas in another case Cp gives only slightly better activity (product 3). However, in general, the relative catalytic performance of the different precatalysts does not vary when the base is changed. Understanding the relative activity of (η5-Cp)Pd(IPr)Cl (Cp) In order to

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

• are tolerated. Keywords: 4-aminoantipyrine; arylboronic acids; biaryls; cross-coupling; palladium(II) complex; Introduction The sp2–sp2 carbon–carbon bond formation through cross-coupling reactions catalyzed by metal complexes has emerged as a powerful tool in organic synthesis [1][2][3][4][5][6

• ]. The palladium-catalyzed cross-coupling of arylboronic acid and aryl halides in the Suzuki–Miyaura (SM) reaction is one of the most popular and important methods to obtain biaryls, which are essential structures of many important compounds such as natural products [7], agrochemicals [8

• . The biaryls are obtained in moderate to high yield. Results and Discussion The synthesis of the 4-APP–Pd(II) complex was carried out using a convenient one-pot procedure, as reported in the literature for other ligands [22], by combining Li2PdCl4, 4-AAP and NaOAc in methanol at room temperature

P(O)R₂-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

• Rong-Bin Hu,
• Hong-Li Wang,
• Hong-Yu Zhang,
• Heng Zhang,
• Yan-Na Ma and
• Shang-dong Yang

Beilstein J. Org. Chem. 2014, 10, 2071–2076, doi:10.3762/bjoc.10.215

• . China 10.3762/bjoc.10.215 Abstract Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C–H activation; the functionalized

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

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

• various applications of eosin Y to visible light-driven syntheses of biaryls [15], stilbenes [16], benzothiophenes [17], α-phenylketones [18], phenanthrenes [19], arylsulfides [20] and arylboron pinacolates [21] (Scheme 1). Numerous mechanistic studies have been performed at reactions with organometallic

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

• Affording valued biaryls and heterobiaryls, namely ubiquitous chemical moieties in pharmaceuticals, natural products, photoactive species and many other functional molecules, the Suzuki–Miyaura cross-coupling reaction is widely employed by the fine chemicals and pharmaceutical industries [1]. The reaction

• 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

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

• 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

Photoinduced synthesis of unsymmetrical diaryl selenides from triarylbismuthines and diaryl diselenides

• Yohsuke Kobiki,
• Shin-ichi Kawaguchi,
• Takashi Ohe and
• Akiya Ogawa

Beilstein J. Org. Chem. 2013, 9, 1141–1147, doi:10.3762/bjoc.9.127

• this solid is a bismuth residue, which can consist of bismuth oxides and/or bismuth selenides. Moreover, it may form biaryls (Ar–Ar) as byproducts, but no biaryl was observed after the reaction. Conclusion We have found that the photoinduced reaction of diaryl diselenides with triarylbismuthines

Bromine–lithium exchange: An efficient tool in the modular construction of biaryl ligands

• Laurence Bonnafoux,
• Frédéric R. Leroux and
• Françoise Colobert

Beilstein J. Org. Chem. 2011, 7, 1278–1287, doi:10.3762/bjoc.7.148

• Laurence Bonnafoux Frederic R. Leroux Francoise Colobert Laboratoire de stéréochimie, UMR 7509, CNRS-Université de Strasbourg, ECPM, 25 rue Becquerel, F-67087 Strasbourg Cedex 02, France 10.3762/bjoc.7.148 Abstract Regioselective bromine–lithium exchange reactions on polybrominated biaryls enable

• analogues. So far, such a process, based on the effective discrimination between bromine atoms as a function of their chemical environment, has been observed only sporadically. Keywords: biaryl; bromine–lithium exchange; ligand; lithiation; phosphine; Introduction Atropisomeric biaryls are important

• stereoelectronic profile of a ligand. Most frequently, biaryls are prepared through transition metal-catalyzed reactions of suitable functionalized starting materials [17][18][19][20][21][22]. Although these methods are well established, alternatives are investigated in order to avoid expensive transition metals

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• sp, sp2, and sp3, and –O, –N, and –S bonds are made to the aromatic ring carbon [25]. These strategies rapidly furnish biaryls/heterobiaryls, and condensed complex aromatics/heteroaromatics whose construction by previous generation methods (e.g., diazonium and radical coupling) has been clearly

Cationic gold(I) axially chiral biaryl bisphosphine complex-catalyzed atropselective synthesis of heterobiaryls

• Tetsuro Shibuya,
• Kyosuke Nakamura and
• Ken Tanaka

Beilstein J. Org. Chem. 2011, 7, 944–950, doi:10.3762/bjoc.7.105

• biaryls [5][6][7]. These reports clearly demonstrated the utility of the asymmetric annulation strategy for the atropselective biaryl synthesis [8]. As an alternative asymmetric annulation method for the atropselective biaryl synthesis, we turned our attention to transition-metal catalyzed

Studies on Pd/NiFe₂O₄ catalyzed ligand-free Suzuki reaction in aqueous phase: synthesis of biaryls, terphenyls and polyaryls

• Sanjay R. Borhade and
• Suresh B. Waghmode

Beilstein J. Org. Chem. 2011, 7, 310–319, doi:10.3762/bjoc.7.41

• arylboronic acids is one of the most important and powerful methods for the construction of biaryls and polyaryls due to its compatibility towards a wide range of functional groups on both partners [5][6][7][8][9][10]. The resulting Suzuki products have found numerous applications in the synthesis of natural

• products, pharmaceutical intermediates, pesticides, advanced materials and liquid crystals [8][9][10]. These applications, in turn, have led to the production of biaryls and polyaryls on the industrial scale [11]. The Suzuki reaction is usually performed with homogeneous palladium catalysts in the presence

• reaction times compared to arylboronic acids, probably as a result of strong coordination of the heterocyclic nitrogen with Pd metal. Ortho substituted aryl iodides required slightly longer reaction times to give the corresponding biaryls. The coupling of 4-chloroiodobenzene with phenylboronic acid gave

Suzuki–Miyaura cross-coupling reaction of 1-aryltriazenes with arylboronic acids catalyzed by a recyclable polymer-supported N-heterocyclic carbene–palladium complex catalyst

• Guangming Nan,
• Fang Ren and
• Meiming Luo

Beilstein J. Org. Chem. 2010, 6, No. 70, doi:10.3762/bjoc.6.70

• . Various aryltriazenes were investigated as electrophilic substrates at room temperature to give biaryls in good to excellent yields and showed good chemoselectivity over aryl halides in the reactions. Keywords: 1-aryltriazenes; N-heterocyclic carbene–palladium complex; polymer-supported catalyst

• ; recyclable catalyst; Suzuki–Miyaura reaction; Introduction The unsymmetrical biaryls feature in a diverse range of organic compounds, such as natural products, advanced materials, liquid crystals, ligands and molecules of medicinal interest [1][2][3][4]. The palladium-catalyzed Suzuki–Miyaura cross-coupling

• reaction has evolved as a powerful synthetic tool for the synthesis of unsymmetrical biaryls in both academic laboratories and industry [5][6][7][8]. Most of the reported Suzuki–Miyaura reactions are based on the use of aryl halides and triflates, and recently sulfonates and carboxylates, as the

Solvent-free and time-efficient Suzuki–Miyaura reaction in a ball mill: the solid reagent system KF–Al₂O₃ under inspection

• Franziska Bernhardt,
• Ronald Trotzki,
• Tony Szuppa,
• Achim Stolle and
• Bernd Ondruschka

Beilstein J. Org. Chem. 2010, 6, No. 7, doi:10.3762/bjoc.6.7

• 2 yielding substituted biaryls 3 under ball milling conditions (palladium-catalyzed and SRS-assisted). Representative experimental procedures for the preparation of KF–Al2O3. Characteristics of the base components applied in Suzuki–Miyaura reactions as SRS. Influence of preparation and storage

Chiral amplification in a cyanobiphenyl nematic liquid crystal doped with helicene-like derivatives

• Alberta Ferrarini,
• Silvia Pieraccini,
• Stefano Masiero and
• Gian Piero Spada

Beilstein J. Org. Chem. 2009, 5, No. 50, doi:10.3762/bjoc.5.50

• designed as pseudo-P when the two phenyl rings are arranged in such a way that a clockwise rotation (<90°) of the ring closer to the observer is required to obtain the coplanarity of the two aromatic planes). In most cases, (pseudo-P)-biaryls induce (P)-cholesterics; however, the relationship between

Synthesis of unsymmetrically substituted biaryls via sequential lithiation of dibromobiaryls using integrated microflow systems

• Aiichiro Nagaki,
• Naofumi Takabayashi,
• Yutaka Tomida and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2009, 5, No. 16, doi:10.3762/bjoc.5.16

• micromixers and four microtube reactors to obtain unsymmetrically substituted biaryl compounds. Keywords: dibromobiaryls; fast mixing; integrated microflow system; selective lithiation; unsymmetrically substituted biaryls; Introduction Unsymmetrical biaryls have received significant research interest

• biaryls [2][3][4][5][6][7][8][9]. Selective monolithiation of dihalobiaryls also seems to be useful for synthesis of unsymmetrically substituted biaryls because the remaining halogen atom can be utilized for further transformations [10][11][12]. However, halogen-lithium exchange reactions of dihalobiaryls

• ][53]. Recently, we reported that selective monolithiation can be achieved by extremely fast 1:1 micromixing of dibromobiaryls and n-butyllithium using microflow systems [54]. The successful results prompted us to perform a study on the synthesis of unsymmetrically substituted biaryls via sequential