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

• complex catalyzes the atropselective intramolecular hydroarylation of alkynes leading to enantioenriched axially chiral 4-aryl-2-quinolinones and 4-arylcoumarins with up to 61% ee. Keywords: asymmetric catalysis; axial chirality; gold; heterobiaryls; hydroarylation; Introduction Atropselective biaryl

• 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

• from N-alkenyl-arylethynylamides was thus investigated. Although cationic gold(I)/axially chiral biaryl bisphosphine complexes [19][20][21][22][23][24][25][26][27][28][29][30][31] have been frequently employed in asymmetric variants of cationic gold(I) catalyses [32][33][34][35][36][37][38], including

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

Synthesis of chiral mono(N-heterocyclic carbene) palladium and gold complexes with a 1,1'-biphenyl scaffold and their applications in catalysis

• Lian-jun Liu,
• Feijun Wang,
• Wenfeng Wang,
• Mei-xin Zhao and
• Min Shi

Beilstein J. Org. Chem. 2011, 7, 555–564, doi:10.3762/bjoc.7.64

• catalysts in chiral induction reactions [19][20][21][22][23][24][25]. The axially chiral biaryl framework, widely used in the design of chiral ligands such as BINAP [26][27], BINOL [28][29], and boxax [30], has proved to be very rigid, and was introduced in the development of NHC ligands by the Hoveyda

• complex 2 with a biaryl framework, in which one of biaryl groups bearing a substituent might provide steric hindrance to limit the rotation of the N–Ar bond. Herein we wish to report the synthesis of novel chiral [(NHC)Pd(allyl)I] and mono(NHC)–Au complexes bearing an axially chiral biphenyl framework

• with sterically hindered N-substituents. NHCs with axially chiral biaryl frameworks. ORTEP drawing of NHC–Pd(II) complex (S)-7a with thermal ellipsoids at the 30% probability level. Selected bond distances (Å) and angles (deg): Pd–C1 = 2.050(5), Pd–C25 = 2.154(7), Pd–C26 = 2.128(9), Pd–C27 = 2.168(8

Air-stable, recyclable, and time-efficient diphenylphosphinite cellulose-supported palladium nanoparticles as a catalyst for Suzuki–Miyaura reactions

• Qingwei Du and
• Yiqun Li

Beilstein J. Org. Chem. 2011, 7, 378–385, doi:10.3762/bjoc.7.48

• the most powerful tools for the preparation of unsymmetrical biaryl compounds [4] and has been applied to many areas, including pharmaceuticals, herbicides, and natural products, as well as in the fields of engineering materials, such as conducting polymers, molecular wires, liquid crystals and

• stirred and heated under reflux. After the reaction was judged to be complete by TLC analysis, the catalyst was removed by filtration, washed with ethanol (3 × 4 cm3) and dried under vacuum for the next run. The organic fractions were then concentrated on a rotary evaporator to obtain the desired biaryl

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

• short reaction times. Bromobenzene and electron rich aryl bromides required a higher loading of palladium (1.0 mol %) to give comparable results. Both electron rich and electron deficient arylboronic acids gave biaryl products in good to excellent yields. Heterocyclic boronic acids required longer

• reaction mixture was analyzed by GC, the amount of 4-iodotoluene was set to 100% and the reaction was performed under the identical reaction conditions. It was observed that 54% of 4-iodotoluene was converted to the corresponding biaryl after 60 min and the Pd content detected in the filtrate was 2.3 ppm

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• -aryl bond formation, and many examples illustrate their wide application in organic synthesis. The chelating phosphines BINAP, DPPF [17] and DtBPF [18], commonly used for the Buchwald–Hartwig amination, were recently displaced by the biaryl-(dialkyl)phosphine or arylphosphinepyrrole ligands [18][19][20

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

• absence of catalyst 1 (Table 2, entry 1). The yield of the corresponding biaryl product increased with the catalyst loading (Table 2, entries 2, 3, 4). A high yield of 92% was obtained when 2.0 mol % Pd was employed (Table 2, entry 5) whilst Pd loadings of greater than 2.0 mol % Pd did not lead to

• improved yields (Table 2, entry 6). Table 3 shows the effect of the molar ratio of phenylboronic acid to 1-(3-nitrophenyl)-2-(pyrrolidin-1-yl)diazene on the reaction yield. A yield of 77% was obtained when the molar ratio was 1.25 (Table 3, entry 1). The yield of the corresponding biaryl product increased

• biaryl products in good to excellent yields. The electronic nature of substituents and steric factors of both substrates affected the yields of the cross-coupling products. Electron-withdrawing substituents on the 1-aryltriazenes and electron-donating groups on the arylboronic acids gave better yields of

Efficient and improved synthesis of Telmisartan

• A. Sanjeev Kumar,
• Samir Ghosh and
• G. N. Mehta

Beilstein J. Org. Chem. 2010, 6, No. 25, doi:10.3762/bjoc.6.25

• , all of which contain a characteristic ortho functionalized biaryl moiety. Telmisartan (1, Boehringer Ingelheim, Micardis®) (Figure 1) is an important member of this class of top-selling drugs because it has the strongest binding affinity to the AT1 receptor, an excellent bioavailability, and a once

• in the final step [6]. However, the main shortcomings of the synthesis remained, namely, the unsatisfactory regioselectivity in the alkylation of 8 with 4 and the intricate synthesis of the biaryl intermediate 7. In the original protocol, the latter was synthesized via an Ullmann coupling of the aryl

• major bond disconnections. We realized biaryl synthesis and reductive amination are the key steps, and have the potential to overcome both of these weaknesses. Results and Discussion We identified 4-formylphenylboronic acid (10) and 2-(2-bromophenyl)-4,4-dimethyl-2-oxazoline (11) [12] as the ideal

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• . Furthermore, an efficient intramolecular variant of this procedure starting from biaryl benzyl alcohol 23 led to substituted fluorenes 24 which have shown to be valuable scaffolds for blue light emitting polymers (Scheme 11A) [46]. A similar route to fluorenes and other annulated cycloalkanes 26 was

Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

• Andreas Speicher,
• Timo Backes,
• Kerstin Hesidens and
• Jürgen Kolz

Beilstein J. Org. Chem. 2009, 5, No. 71, doi:10.3762/bjoc.5.71

• molecular framework of the subtype “isoplagiochin” is of substantial structural interest because of the chirality of the entire molecule, which arises from two biaryl axes in combination with two helical two-carbon units in a cyclic arrangement. From a structural as well as a synthetic point of view we

• report on the total synthesis of compounds which possess more rigid two-carbon biaryl bridges like stilbene (E or Z) or even tolane moieties which were introduced starting with a Sonogashira protocol. The McMurry method proved to be a powerful tool for the cyclization to these considerably ring-strained

• macrocycles. Keywords: axially chiral biaryl; isoplagiochin; macrocycle; ring strain; total synthesis; Introduction The cyclic bisbibenzyls isoplagiochin C (1) and D (2) were isolated from the liverworts Plagiochila fruticosa [1], Plagiochila deflexa [2], Herbertus sakuraii [3] and Lepidozia fauriana [4

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

• relationship between molecular structure, intermolecular interactions, and mesoscale organization. It is known that axially chiral or helical-shaped molecules with reduced conformational disorder are good candidates for high helical twisting power derivatives. In particular, biaryl derivatives are known to be

• efficient chiral inducers in biaryl nematic mesophases. In this paper, we focus on a new series of helicene-like molecules of known absolute configuration. We have integrated cholesteric pitch measurements with geometry optimization by DFT calculations and analysis of the twisting ability by the Surface

• standard Quantum Mechanical (QM) tools. It is known that axially chiral or helical-shaped molecules with reduced conformational disorder are good candidates for high HTP derivatives [2][4][6]. In particular, biaryl derivatives have been described as efficient chiral inducers in biaryl nematic mesophases

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

• summarized in Table 4, the sequential introductions of two electrophiles were achieved successfully with various combinations of electrophiles without isolation of monobromo biaryl compound. It is interesting to note that the use of an aldehyde (E1) and methyl chlorocarbonate (E2) as electrophiles led to

• microtube reactors shown in Figure 3. As summarized in Table 7, the sequential introductions of two electrophiles were achieved successfully without isolation of a monobromo biaryl compound. Br-Li Exchange Reaction of Other Dibromobiaryls and 2,2′-Dibromobibenzyl (43) We next examined the reactions of other

Asymmetric synthesis of biaryl atropisomers by dynamic resolution on condensation of biaryl aldehydes with (−)-ephedrine or a proline- derived diamine

• Ann Bracegirdle,
• Jonathan Clayden and
• Lai Wah Lai

Beilstein J. Org. Chem. 2008, 4, No. 47, doi:10.3762/bjoc.4.47

• Ann Bracegirdle Jonathan Clayden Lai Wah Lai School of Chemistry, University of Manchester, Oxford Rd., Manchester M13 9PL, UK 10.3762/bjoc.4.47 Abstract Atropisomeric biaryl aldehydes undergo diastereoselective condensation with (−)-ephedrine and with a proline-derived diamine, with selectivity

• % yield. Hydrolysis and reduction of the major diastereoisomeric product of the reaction yields atropisomeric biaryls in >99:1 enantiomeric ratios. Keywords: atropisomer; biaryl; dynamic resolution; ephedrine; imdazolidine; oxazolidine; Introduction Atropisomeric biaryl compounds have proved to be among

• the most successful of all chiral ligands for metal-catalysed asymmetric transformations [1][2]. Many biaryl ligands have been obtained in enantiomerically pure form by means of resolution [3], but there are also a number of important enantioselective methods for the synthesis of biaryls [4][5][6][7

Synthesis of deep- cavity fluorous calix[4]arenes as molecular recognition scaffolds

• Maksim Osipov,
• Qianli Chu,
• Steven J. Geib,
• Dennis P. Curran and
• Stephen G. Weber

Beilstein J. Org. Chem. 2008, 4, No. 36, doi:10.3762/bjoc.4.36

• showed diminished yields due to product occlusion with the precipitation of silver iodide. The reactivity of 5 in the Kumada cross-coupling reaction was next investigated. Treatment of 5 with PdCl2(dppf) followed by phenylmagnesium bromide provided the biaryl 6 as the only observed product in 75% yield

• (Scheme 3). With simple cross coupling accomplished, coupling with a functionalized phenyl ring was investigated. Therefore, 5 was treated with an excess of Grignard 7 in the presence of PdCl2(dppf) to provide a mixture of two inseparable compounds, the target biaryl 8, and the dimer of 7, as observed by

Control of asymmetric biaryl conformations with terpenol moieties: Syntheses, structures and energetics of new enantiopure C₂-symmetric diols

• Y. Alpagut,
• B. Goldfuss and
• J.-M. Neudörfl

Beilstein J. Org. Chem. 2008, 4, No. 25, doi:10.3762/bjoc.4.25

• : chiral diols; hydrogen bonds; axial chirality; terpenes; Introduction Enantiopure biaryl systems with flexible chiral axes are widespread, e.g. in pharmacological natural products or as ligands in enantioselective catalyses [1]. Chelating C2-symmetric diols such as BINOLs [2][3][4] and TADDOLs [5][6

• ] are often employed as chiral ligands in enantioselective synthesis. We recently reported the synthesis and the X-ray crystal structure of (M)-BIFOL [7] (biphenyl-2,2′-bisfenchol, Scheme 1) and its derivatives [8][9][10][11]. (M)-BIFOL exhibits, in a similar way as BINOLs, a flexible biaryl axis with M

• ) calculations of the chelating diols prove that the experimentally observed biaryl conformations are indeed intrinsically favored, their alternative diastereomeric biphenyl conformers are all energetically disfavored. (M)-BIMOL is computed to be 1.3 kcal/mol, (P)-BIVOL is 5.1 kcal/mol, (P)-BICOL is 5.8 kcal/mol

A convenient catalyst system for microwave accelerated cross- coupling of a range of aryl boronic acids with aryl chlorides

• Matthew L. Clarke,
• Marcia B. France,
• Jose A. Fuentes,
• Edward J. Milton and
• Geoffrey J. Roff

Beilstein J. Org. Chem. 2007, 3, No. 18, doi:10.1186/1860-5397-3-18

• biaryl synthesis and is widely applied in organic chemistry. [1][2][3][4][5][6] In the last 10 years, there has been intense research interest in Suzuki reactions of aryl chloride substrates since these substrates are cheaper and more widely available than aryl bromides. A range of catalysts now exist

• biaryl products (see Supporting Information File 1 for experimental data). There has been some interest in the cross-coupling of fluorinated nucleophiles due to the application of fluoroaryl substituents in medicinal chemistry and in liquid crystals. [30][31][32][33][34] The Buchwald group recently

• understanding, stoichiometric experiments between [Pd(dppf)Cl2] and boronic acids were carried out (Scheme 4). Given that [Pd(dppf)(Ar)2] species rapidly reductively eliminate,[41] successful transmetalation should result in significant amounts of the symmetrical biaryl (alongside a number of other species such

A superior P-H phosphonite: Asymmetric allylic substitutions with fenchol- based palladium catalysts

• Bernd Goldfuss,
• Thomas Löschmann,
• Tina Kop-Weiershausen,
• Jörg Neudörfl and
• Frank Rominger

Beilstein J. Org. Chem. 2006, 2, No. 7, doi:10.1186/1860-5397-2-7

• computational transition structure analyses, these phenyl and anisyl phosphinites are not "monodentate" but form chelate complexes via π-coordination. Biphenyl-2,2'-bisfenchol (BIFOL)[13] was developed as combination of a flexible biaryl axis (as in BINOL) and sterically crowded hydroxy groups (as in TADDOLs

An exceptional P-H phosphonite: Biphenyl- 2,2'-bisfenchylchlorophosphite and derived ligands (BIFOPs) in enantioselective copper- catalyzed 1,4-additions

• T. Kop-Weiershausen,
• J. Lex,
• J.-M. Neudörfl and
• B. Goldfuss

Beilstein J. Org. Chem. 2005, 1, No. 6, doi:10.1186/1860-5397-1-6

• , Scheme 3), which are air stable (no hydrolysis or oxidation) over weeks, crystalline and analyzable via X-ray diffraction. [73][74][75][76] In close analogy to the hydrogen bonded M-BIFOL, [68][69][70][71][72] only minus-(M)-conformations of biaryl axes are found in these BIFOP

• moiety in BIFOP-Cl (1). The geometries of all BIFOP-derivatives are remarkable with respect to their biaryl-angles, the fenchyl-aryl-angles, the pyramidality at the phosphorus atoms as well as the positions of the phosphorus atom in the hydrophobic fenchane cavities (Scheme 4, Table 2). A strong

• preference for the minus (M)-biaryl conformation was found in BIFOL (Scheme 3) and was attributed to hydrogen bond linked chiral fenchole units, in the solide state and in solution. [68][69][70][71][72] Similarly, all phosphorus linked BIFOPs exhibit M-biarly axes with dihedral angles varying from -91° to