Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• contrast, only very few reports deal with the oxidative cyclization of nitrogen-containing biaryl intermediates. Ravi Kumar and Satyanarayana mentioned two successful control reactions using 2-phenylbenzylamine and 2-iminomethylbiphenyl with 5 mol % Pd(OAc)2 and 2 equivalents Ag2O in acetic acid at 140 °C

• of biaryl aldehyde intermediates 8, reduction [60] in the case of nitriles 14, or Boc deprotection [61] for 14k, m, o according to standard protocols (Schemes 4–7; for details, see Supporting Information File 1). Although it may seem counterintuitive to first convert aldehydes 8 and nitriles 14 into

• aryllithium intermediate. For the synthesis of the benzylamine unit, commercially available nitrile 19 was reacted with NBS to regioselectively introduce a bromo substituent to give bromobenzonitrile 20 in a yield of 51% [65]. Biaryl 21 was constructed via a Suzuki coupling [57] of 18 and 20 in 41% yield. As

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• uncommon biaryl axis with a pyrrole ring as one of the components, the pyrrole ring itself is created in an unusual manner, and further functionalization of the pyrrole ring is possible. Since both classes of azabicyclic product are well represented in compounds of pharmaceutical interest as well as in

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• ], rhodium-mediated alkyne [2 + 2 + 2] cycloaddition reactions [3], and the palladium-catalysed aerobic domino Suzuki coupling/Michael addition reaction [4]. The most attractive and common strategies to phenanthridines rely on intramolecular cyclizations of various ortho-functionalized biaryl precursors

• , such as ionic liquid- and transition metal-catalyzed and other metal-free transformations [1]. A strategically diverse route to phenanthridines involves intramolecular cyclization of biaryl oximes, allowing for the formation of a new C–N bond. Such a strategy was explored by Deb and Yoshikai in the Fe

• the synthesis of the simple phenanthridine natural product trisphaeridine (3). Results and Discussion To investigate the scope and limitations of the reaction we initially opted to prepare a number of biaryl substrates possessing one aromatic electron accepting ring possessing a variety of methoxy

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• compounds and biaryl chiral auxiliaries. Also, the oxidative coupling of phenolic substrates has been reported to be mediated by vanadium complexes such as VCl4, VOCl3, and VOF3, among others. For instance, an intramolecular coupling of phenolic moieties using VOF3 has been reported as a final step in the

• compounds to produce the corresponding biaryl products with high enantiopurity using vanadium chelated with chiral ligands, such as tridentate asymmetric imine ligands, have been reported. For instance, (S)-binol derivatives could be successfully prepared from 2-naphthols using a dimeric vanadium complex

• -containing substrates, and its high efficiency makes it an excellent methodology for late-stage modifications (Scheme 20D). Biaryl structures are present in several important drugs currently commercially available (57, 58, and 59, Scheme 21A) [141] and synthetic methods to achieve the aryl–aryl connection

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• -aryl substituent to the berberine chromophore. The latter has been shown to operate also in resembling cationic, biaryl-type dyes [42][43]. Along the same lines, the low intrinsic emission quantum yield of the parent berberine (1a) has been suggested to result from an internal charge transfer (ICT

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• azepinone 22 and exemplified a modified Ugi reaction (four-component reaction). The aldehyde and acid component of the Ugi reaction was functionalized on the same biaryl ring employing a Suzuki–Miyaura coupling. The authors advocated the use of microwave as it consistently increased the yield from 49% to 82

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• fluorine, which helps to generate cations but does not affect cationic reactions [23][24][25][26][27]. Thus, HFIP greatly facilitates reactions via cationic intermediates [28]. In the presence of a catalytic amount of trifluoromethanesulfonic acid in HFIP, (biaryl-2-yl)acetoaldehydes or their acetal

• derivatives readily underwent intramolecular Friedel–Crafts-type C–C bond formation followed by dehydration or alcohol elimination, leading to the construction of benzene rings in the biaryl systems (Scheme 2) [20][21]. The reaction proceeded via oxocarbenium ion intermediates stabilized by HFIP. This method

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• , affording biaryl species 161. Using this strategy, several trifluoromethyl ketones 162 and alcohols 163 bearing heteroaryl substituents (i.e., benzothiazole, quinoline, isoquinoline, benzimidazole, or imidazole) prone to be protonated were elegantly converted into the corresponding alcohols 163 and biphenyl

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• a 73% yield. The Suzuki coupling of boronate 6a and aryl bromide 9a using palladium acetate and cesium carbonate in the presence of the ligand SPhos [25] yielded biaryl 10a with virtually quantitative yield (98%, Scheme 4). Unfortunately, the removal of non-identified byproducts and of 9a (which had

• the product with 55% yield. The O-benzylation of phenol 8 furnishing the bromide 9b was accomplished with virtually quantitative yield. Suzuki coupling of the benzyl-protected compounds 6b and 9b led to biaryl 10b with 89% yield; it was deprotected with palladium on charcoal under eight bar hydrogen

• , K2CO3, DMF/acetone 1:2, 80 °C, 43 h (98%). Final steps in the synthesis of biaryl 1. Conditions: h) Pd(OAc)2, SPhos, Cs2CO3, dioxane/H2O 7:1, 70 °C, 18 h, (R = TBS: 98%, containing non-separable impurities; R = Bn: 89%) ; i) R = Bn: Pd/C (10%), H2, THF, 8 bar, 24 h, 40 °C (88%). NMR data of natural and

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• synthesis of biarenes has been developed. The approach is based on the photoextrusion of a phosphate moiety occurring upon irradiation of biaryl- and triaryl phosphates. The reaction involves an exciplex as the intermediate and it is especially suitable for the preparation of electron-rich biarenes

• active compound is a common practice in medicinal chemistry [1][2][3]. In particular, the biaryl moiety is a privileged scaffold largely present in the skeleton of natural substances [4][5][6][7] and in useful chiral ligands [8][9][10]. The synthesis of biaryl derivatives remains, however, a considerable

• intermediates (triplet aryl cations [28][29] or aryl radicals [30][31]). As for the former case, the intermolecular formation of a biaryl arose from the photoheterolysis of an Ar–N bond (in arene diazonium salts or their derivatives [32][33]), of an Ar–Cl bond [34][35], of an Ar–O bond (in aryl phosphates [36

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• challenges since the solubility of CAN in organic solvents determines the likelihood of nitration or oxidative dimerization [1]. It was found that dry acetonitrile was more conducive to nitration, whereas methanol afforded the desired biaryl in 55% yield. In contrast to CAN, both V2O5 and CrO3 required

• % and 59% yields, respectively (Table 1). Following the successful oxidative dimerization of 1,2,4-trimethoxynaphthalene 17 to biaryl 18, the biaryl was converted quantitatively to binaphthyl 16 in the presence of an aqueous solution of CAN at 0 °C. Alternatively, the binaphthylquinone 16 was

• FeCl3·SiO2. Treatment of the polyphenol with PIDA (1.5 equiv) in boron trifluoride etherate (1.5 mL) at room temperature proved to be the most successful dimerization protocol, as the dimeric precursor 19 was formed in 80% yield after 16 hours. The biaryl 19 was converted quantitatively to the natural

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• expected biaryl product. In parallel, the photocatalytic cycle warrants the mild generation of the Ar• radical as well as the key Au(II)/Au(III) oxidation. More recently, an alternative strategy for the straight, non-directed arylation of (hetero)arenes was reported by Ackermann (Figure 44) [105

• transfer generate the aryl radical together with a cationic Mn species. The addition of the aryl radical to the (hetero)aromatic substrate affords a radical biaryl intermediate that provides the expected coupling product after oxidation and deprotonation. C–H activation of heterocyclic substrates The panel

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• occurring on a stilbene diazonium salt (e.g., 1.1+) with the intermediacy of an aryl radical [40]. Alternative strategies for the synthesis of phenanthrenes have been later reported, including the adoption of [4 + 2] benzannulations between biaryl derivatives and alkynes [41][42]. Scheme 2 illustrates one

• cyclized to form the desired phenanthridine 11.4 in excellent yield. Notably, the reaction could be readily applied to benzoimines having different substituents on the aromatic ring bearing the amino group [73]. Glycine derivatives having a biaryl group attached to the N-terminus were successfully

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• and subjected to metabolite analysis, which resulted in the discovery of a novel cyclopeptide, pseudosporamide (1), along with three new oligomycin-class polyketides, pseudosporamicins A–C (2–4). The unusual structure of compound 1, featured by a biaryl-bond bridging across a tripeptide scaffold, N

• -acetyl-ʟ-Tyr-ʟ-Pro-ʟ-Trp, was determined by a combination of spectroscopic analyses, chemical derivatization, ECD calculation, and DFT-based theoretical chemical shift calculation, revealing the presence of an (Sa)-axial chirality around the biaryl bond. Compounds 2–4 lacked hydroxylation on the side

• comparison of experimental and simulated ECD spectra [26][27]. Quite interestingly, the DFT calculation suggested that 1a and 1b would possess the opposite axial chirality around the biaryl bond between C-6 and C-7'': Ra for 1a and Sa for 1b as dominant atropisomers (Figure 4). This conformational difference

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• Abstract Pd-catalyzed asymmetric Suzuki–Miyaura couplings of 3-methyl-2-bromophenylamides, 3-methyl-2-bromo-1-nitrobenzene and 1-naphthaleneboronic acids have been successfully developed and the corresponding axially chiral biaryl compounds were obtained in very high yields (up to 99%) with good

• ], especially on how to obtain the large steric axially chiral biaryl with a high yield and good enantioselectivity through those coupling strategies [13]. Therefore, based on our previous research [60][61][62][63][64][65], we herein present a new method through which those large steric axially chiral biaryl

• structure (Scheme 4). Conclusion In summary, a Pd-catalyzed asymmetric Suzuki–Miyaura coupling of 3-methyl-2-bromophenylamides or 3-methyl-2-bromo-1-nitrobenzene and 1-naphthaleneboronic acids has been successfully developed and the corresponding axially chiral biaryl compounds were obtained in very high

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• of biaryl products with triazole. For this, 4-bromoaryl derivatives were initially treated with phenylboronic acid. The biaryl derivatives were then reacted with phenylacetylene to give triazole-containing biaryl compounds in high yields. Stilbenes were also applied in the reaction under similar

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• groups to form biaryl frameworks. Traditionally, transition-metal-catalyzed cross-coupling reactions of aryl halides or pseudohalides with arylmetal reagents have been employed for the connection of two aryl units [5][6][7][8][9]. However, in search of more efficient synthetic routes, C–H arylation

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• a challenging task due to the inaccessibility of the corresponding 7-halonaphthalene substrates [12]. Recently, transition metal-catalyzed C–H bond functionalization has emerged as a powerful tool to construct various biaryl skeletons [13][14][15][16][17]. The direct C7−H arylation of 1-naphthoic

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• 9,9-dihydro-5-silafluorene (2f), which gave the spiro-type phenoxasilin 3f in 96% yield. We then investigated the scope of the starting biaryl ethers used in the reaction as well as related derivatives thereof using dihydrodiphenylsilane (2a, Scheme 3). Pyrrolidine-substituted diaryl ether 1b was

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• (NHCs) have proved to be versatile ligands in organometallic chemistry [82]. The synthesis of sterically crowded biaryl ligands is still a challenging task, especially under mild reaction conditions. The diphosphine complexes of imidazolylphosphines proved to be an alternative towards the coupling of

• sterically crowded biaryl ligands as they showed outstanding performances [8]. Phosphines with imidazole and imidazoline functional groups present some interesting features. The imidazolium functionality mimics active sites in biological molecules [83][84]. The ionic nature adds another dimension to the

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• . The crystal of 4b is classified into a space group P4322 (tetragonal) with a biaryl torsion angle of 74.4° (Figure 4b). A considerable intermolecular π–π stacking interaction was observed in between its polyaromatic fragments whose distance is approximately 3.44 Å. The polycyclic subunits overlap each

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• formation of carbazoles from biaryl derivatives. Mechanism for the synthesis of phenol derivatives with photoredox catalyst 8. Possible mechanism for the generation of phenols with the aid of photoredox catalyst 5. Proposed mechanism for the synthesis of monobrominated compounds. Mechanism for the synthesis

• olefination. C–H olefination of phenolic ethers. Decarboxylative acylation of acetanilides. Synthesis of fluorenone derivatives by intramolecular deoxygenative acylation of biaryl carboxylic acids. Synthesis of benzothiazoles via aerobic C–H thiolation. Synthesis of benzothiazoles via oxidant-free C–H

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• colchicine per se, aiming at compounds where one isomer would be almost biologically inactive such that light can be used to effect a photoisomerisation-based switch-on/switch-off of bioactivity. The end-to-end distance of the HTI scaffold is significantly longer than that in either the biaryl colchicine or

• different substituent patterns to those of colchicine, and attempted to rationally determine these. Firstly, since the HTI scaffold is longer than a biaryl motif but should occupy a similar volume in the pocket, we assumed that we would have to reduce the substituent bulk present on colchicine

• scaffold could best be reduced in volume by "shortening" this substituent, maintaining the abovementioned non-polar interaction. Secondly, since the torsion angle of the HTI is far lower than that of (Z)-stilbenes or biaryl compounds, we considered that even with shortening, their SARs might not directly

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• . The addition of 1-bromo-4-methoxynaphthalene (1, 0.9 equiv) and K3PO4, and stirring overnight at 110 ºC, afforded the biaryl methyl ether 5 in an 82% yield (Scheme 1). Similarly, Buchwald´s methodology [41] was applied in the synthesis of 7, which was obtained in 70% yield after tetrahydropyran (THP

• ) group deprotection in MeOH/CH2Cl2 using TsOH·H2O as the catalyst (Scheme 2). In a conventional triflation (Tf2O, DMAP cat.), 7 was converted into 8 with a yield of 86%. For the synthesis the triflates 9–11 a one-pot demethylation–triflation sequence was followed (Scheme 2). The treatment of biaryl