Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• ]. In this work, biaryl isocyanates 45 could be converted into phenanthridines 46, and aryl isocyanates 47 could be transformed into benzoxazoles 48 directly in refluxing toluene together with the simultaneous release of carbon dioxide. Presumably these reactions proceeded via iminophosphorane

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• synthesis of 9-methoxycarbonylindolo[3,2-a]carbazole derivatives. The key steps in this approach involved an aromatic amination and an oxidative biaryl coupling. Via the present route, indolo[3,2-a]carbazole derivatives are available in 3–4 steps based on commercially available starting materials. Keywords

• : cyclization; indolo[3,2-a]carbazole; N-arylation; oxidative biaryl coupling; palladium catalysis; Introduction Many biologically active carbazole derivatives are of interest as drug-like templates. The indolo[3,2-a]carbazole skeleton, one of the isomeric indolocarbazoles, was firstly identified from nature

• twofold oxidative cyclization. Findings The oxidative biaryl coupling reaction was originally described over 30 years ago using stoichiometric palladium(II) [9][10]. Quite recently, the reaction has been developed to proceed catalytically and widely applied as an atom economic approach to carbazoles [11

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• low-energy conformers above 2% Boltzmann population, while the number of low-energy conformers was 14 at the applied B97D level (Figure 3). The conformers differed in the orientation of the methoxy groups and the value of the ωC12−C13−C3’−C9’ biaryl torsional angle resulting in different orientations

• of the C-13 indol and dihydro-5aH-[1]benzofuro [2,3-b]indole moieties. The different biaryl torsional angles produced markedly different computed ECD spectra for the conformers having M and P helicity such as the two lowest-energy computed B3LYP/6-31G(d) conformers (Figure 4). The two high-wavelength

• Cotton effects (CEs) had the same sign for conformer A and B, while the lower-wavelength (<250 nm) CEs were significantly different. The hindered rotation along the biaryl linkage may have implied an additional stereogenic element, which would have enabled atropodiastereomers with axial chirality. In

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

• 26. This highlights the greater propensity for 21 to undergo oxidative addition, due to the more reactive iodo-substituent. Further analysis indicated that biaryl 28 strongly absorbs light at 360 nm, and when excited at this wavelength exhibited a red-shifted, intense, emission peaking at 450 nm

• selectivity for the DHQ over the corresponding THQ. Comparison of the reactivity of 6-iodo-THQ 21 and 6-bromo-THQ 26 in a typical Suzuki coupling reaction showed significantly improved conversion in the case of the iodide. The resulting biaryl 28 was found to be highly fluorescent, highlighting the

• addition of DIBAL to 20a.a DIBAL reductions of quinolin-2-ones 23a–e using the optimised method to synthesise 22.a Comparing the reactivity of 6-iodo-THQ 21 and 6-bromo-THQ 26 in a typical Suzuki reaction with boronic ester 27 to give biaryl 28. Supporting Information Supporting information features full

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

• method is based on biaryl cross-coupling between the sodium salt of the terephthalonitrile dianion and a neutral aromatic nitrile in liquid ammonia, and successive alkylation of the long-lived anionic intermediate with alkyl bromides. The reaction is compatible with benzonitriles that contain methyl

• acylation–reduction–halogenation–cyanodehalogenation (Scheme 1) [15], are currently being replaced with methods based on transition-metal-catalyzed biaryl cross-coupling [16][17][18][19][20][21]. This methodology is well developed, compatible with different substituents in the substrate and opens up a new

• propose a one-pot method of the transition-metal-free biaryl cross-coupling for the preparation of 4'-alkyl-4-cyanobiaryls as potentially valuable building blocks [3][4][5][6][7][8][9][20][44] with a variable structure of aromatic moieties (biphenylic, m-terphenylic or phenylnaphthylic), as well as an

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

• Axially chiral biaryl compounds such as BINAP (2,2’-bis(diphenylphosphino)-1,1’-binaphthyl) represent widely used and highly efficient ligands that can be applied in a variety of enantioselective catalytic transformations. Unlike BINAP, the related stereodynamic BIPHEP (2,2’-bis(diphenylphosphino)-1,1

• ) barriers. Functionalization of stereodynamic BIPHEP ligands at the biaryl core offers multiple possibilities. The introduction of achiral, non-covalent interaction sites allows for ee determination of chiral analytes via NMR spectroscopy [21] as well as deracemization of the BIPHEPs with HPLC stationary

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• phosphines, biaryl sulfoxides, or monoaryl monoalkyl sulfoxides. After 1.5 hours, (S)-methyl p-tolyl sulfoxide also showed no conversion (Table 4, entry 5). Since subtle changes in the structure of the enyne substrate could have a significant impact on enantioselectivity, variations of the substituent on

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

• did substrate 1a react with iodide 2a. The corresponding pivaloylanilide is also known to serve as an effective directing group at 130 °C, but at room temperature a poor yield was obtained. Only the dimethylurea analog gave satisfactory conversion to the desired biaryl, thus arriving at optimized

• ][18][19][20][21][22], e.g., HBF4 was found to be critical for generation of biaryl 3h in good yield. The structure of the ortho-arylated product was confirmed by X-ray analysis. While similar reactions, in addition to requiring high temperatures, have typically employed strong acids such as TFA as the

• and arylboronic acid to afford the biaryl in high yield (Scheme 4). Representative results for the reactions between aryl iodides and arylboronic acids are summarized in Figure 2. These arylations tolerate various combinations of substrates and reagents having electron-withdrawing or electron-donating

Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

• Phil M. Pithan,
• David Decker,
• Manlio Sutero Sardo,
• Giampietro Viola and
• Heiko Ihmels

Beilstein J. Org. Chem. 2016, 12, 854–862, doi:10.3762/bjoc.12.84

• Pharmacological Sciences, via Marzolo 5, 35131 Padova, Italy University of Padova, Department of Woman’s and Child’s health, 35128 Padova, Italy 10.3762/bjoc.12.84 Abstract Cationic biaryl derivatives were synthesized by Suzuki–Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids

• . The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained

• ][12]. Along these lines, we established the annelated quinolizinium ion as a versatile platform for the investigation of cationic chemosensors, especially when the chromophore is incorporated within a donor–acceptor system [13]. In particular, we observed that biaryl-type quinolizinium derivatives

N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd–NHC complexes: synthesis, characterization and catalytic activity in carbon–carbon bond-forming reactions

• Senem Akkoç,
• Yetkin Gök,
• İlhan Özer İlhan and
• Veysel Kayser

Beilstein J. Org. Chem. 2016, 12, 81–88, doi:10.3762/bjoc.12.9

• arylation (for 5–8) reactions. As catalysts, they demonstrated a highly efficient route for the formation of asymmetric biaryl compounds even though they were used in very low loading. For example, all compounds displayed good catalytic activity for the C–C bond formation of 4-tert-butylphenylboronic acid

• catalyst for the synthesis of biaryl systems in comparison to the other complexes. We observed that compounds 4 and 7 were more effective than the other compounds as catalyst (Table 3, entry 12; Table 4 entry 11). Conclusion In the present study, a series of benzimidazolium salts (1–4) and PEPPSI Pd–NHC

• -coupling (for 1–8) reactions. Pd-catalyzed direct intermolecular arylation was investigated using electron-poor, electron-rich or electron-neutral substrates. In general, an electron-neutral group was found to be more effective in the formation of biaryl product. Both in situ generated Pd–NHC and PEPPSI Pd

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

• advantage of a chiral (R)-BINOL-bridge to link the two aromatic acids and obtained the coupling product with excellent stereocontrol (up to 100% de) (Scheme 1) [16][17][18][19]. In 1998, Martin et al. [20] applied this strategy to the asymmetric intramolecular biaryl coupling of sugar derivatives carrying 2

• of trans-4,5,9,10-tetrahydroxy-9,10-dihydrophenanthrene at room temperature (Scheme 4). In 1994, Meyers and Nelson [23][24] developed a copper-mediated asymmetric biaryl coupling with oxazoline as the chiral auxiliary to afford the biaryl-coupling products in high diastereomeric purity (dr = 93:7

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

• determined by comparison of the GC responses of product and the internal naphthalene standard. Biaryl products were initially synthesized using literature procedures [15], identified using NMR spectroscopy by comparison to the literature chemical shifts [11] and then these pure samples used to generate

• determined by comparison of the GC responses of product and the internal naphthalene standard. Biaryl products were initially synthesized using literature procedures [15], identified using NMR spectroscopy by comparison to the literature chemical shifts [11] and then these pure samples used to generate

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• related C–H transformation by providing key haloarene intermediates. For examples, in the CuI-catalyzed cross arene dimerization reactions reported by Daugulis et al., the in situ formation of iodoarene intermediate was discovered as the indispensable step during the generation of the biaryl products [65

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• of Grignard reagents to carbonitriles followed by protonation as one of the methods for in situ generation of N–H ketimines, which were directly subjected to Cu-catalyzed aerobic reactions without further purification [54]. In this way, biaryl N–H ketimines generated from biaryl-2-carbonitriles were

• found to undergo copper-catalyzed aerobic aromatic C–H amination (Scheme 3a) [52] or 1,4-aminooxygenation (spirocyclization) (Scheme 3b) [51], affording phenanthridine derivatives and azaspirocyclohexadienones, respectively, depending on the helical sense of the biaryl axis. Herein we report

• of biaryl N–H ketimines under copper-catalyzed aerobic reaction conditions, aiming at the synthesis of 6-membered azaspirocycles such as 3a’ from carbonitrile 1a having a quaternary sp3-hybridized carbon center at its α-position. The reaction of p-tolylmagnesium bromide (2a) to carbonitrile 1a

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

• -coupling reactions with varied degree of success. The most efficient cross-coupling reactions were the Heck reactions with alkenes, a biaryl homocoupling reaction, an azo coupling to electron-rich arenes, and a dediazoniation with TMSN3 in an ionic liquid medium [74][75]. An efficient borylation of

• 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

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• -Diels–Alder reaction involving alkynes, ethyl glyoxalate and ethyl vinyl ether was described for the preparation of 2,3-dihydropyrans [24][25]. Additionally, a tandem CEYM–IMDAR reaction in combination with a final aromatization step was employed for the synthesis of biaryl derivatives [26]. Herein, a

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• carried out at room temperature to generate dioxa[7]paracyclophane 276 with a moderate ee value. The effect of biaryl bis(phosphine) ligands was examined, and it revealed the use of (S)-H8-BINAP afforded the cyclophane 276 with a good yield and optimum ee value. Similarly, they also reported the synthesis

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• has been applied in the synthesis of polycyclic frameworks as well as in the preparation of biologically important compounds [19][20][21][22][23]. Further development of this reaction has led to double C–H activation which has been used for the construction of biaryl compounds [24][25][26][27][28][29

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

• ] (Scheme 11). This synthesis published by Pearson et al. was based on palladium-catalysed picolinamide-directed sequential C–H functionalization reactions, while readily available benzylamine and aryl iodide were used as precursors. In the first step the Pd-catalyzed reaction yielded a biaryl compound. The

• -arylation. The following conventional cross-coupling or directed C–H arylation resulted in substituted phenanthridines. Homolytic aromatic substitution (HAS) by an aryl radical was used for the construction of biaryl motifs as alternative to transition metal-catalysed C–H bond arylation. That approach was

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• demonstrated that this in situ generated reagent works more efficiently in such cyclizations than the more frequently used PIFA reagent. For instance, cyclization of biaryl 35 to carbazole 36 was achieved using this indirect electrochemical approach (Scheme 14) [59][60]. The transformation represents the key

• . Anodic cyclization of dipeptide 25. Anodic cyclization of a dipeptide using an electroauxiliary. Anodic cyclization of hydroxyamino compound 29. Cyclization of unsaturated thioacetals using the ArS(ArSSAr)+ mediator. Cyclization of biaryl 35 to carbazol 36 as key-step of the synthesis of glycozoline (37

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

• efficient. Conclusion In summary, we have developed a mild, efficient and comparatively inexpensive methodology for the synthesis of biaryl compounds. This methodology uses our newly developed 4-AAP–Pd(II) complex as a highly efficient precatalyst and general catalyst for the SM cross-coupling, works

• conditions for relatively short reaction times to afford biaryl compounds in good to excellent yields. The synthetic accessibility and stability under cross-coupling reaction conditions of 4-AAP–Pd(II) make this complex a very promising precatalyst, and we will continue studying its applicability in various

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

• group not only achieved the directing role but also acts as an important component unit of the C–H functionalized products. In this paper, we use the axially chiral biaryl phosphine oxides as substrates and report the synthesis of various chiral phosphorus ligands with high enantiomeric selectivity

• reported operation, the substrates of biaryl derivatives that contained phosphate with axial chirality were obtained in high yields using the Suzuki–Miyaura coupling reaction with the assistance of this versatile chiral ligand [31][32][33][34]. We used substituted naphthylboronic acid or ortho-substituted

• system of P(O)R2-directed Pd-catalyzed C–H activation. These compounds could be transformed to trivalent phosphorus compounds by silane to obtain the corresponding phosphorous ligands. Conclusion In summary, a series of substrates with axially chiral biaryl compounds containing a P(O)Ar2 directing group

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

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

• triarylphosphines 105a as phosphinating agents. This aryl–aryl exchange reaction was compatible with several functional groups such as ketones, aldehydes, esters, nitriles, ethers (Table 11) [192][193][194][195]. Products 106a were isolated in only moderate yields. Several P,N-biaryl ligands were prepared from the