Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• %). This cascade involves an initial Suzuki–Miyaura cross-coupling reaction between 1,8-dihalonaphthalenes and heteroarylboronic acids or esters, followed by an intramolecular C–H arylation under the same conditions to yield the final heterocyclic fluoranthene analogues. The method was further employed to

• )-catalyzed [2 + 2 + 2] cycloaddition reactions with 1,8-dialkynylnaphthalenes to access azafluoranthenes and 2-pyridone-fused naphthalenes [27]. In 2017, we reported a Pd-catalyzed cascade reaction that involves a sequential Suzuki–Miyaura cross-coupling and a subsequent intramolecular C–H arylation between

• analogues via a Pd-catalyzed reaction cascade that consists of a Suzuki–Miyaura cross-coupling reaction followed by an intramolecular C–H arylation. These heterocyclic fluoranthene analogues include a variety of acenaphthylene-fused heteroarenes such as thiophene, furan, benzofuran, pyrazole, pyridine and

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• to chemical biology (Scheme 3a). The utility of the germanyl triazole products was then assessed by subsequent derivatisation of exemplar compounds 15 and 21 (Scheme 3b). Chemoselective Suzuki–Miyaura cross-coupling of the BPin moiety in 21 was straightforward, giving 28 in excellent yield [73

• ]. Similarly, cross-coupling of the GeEt3 moiety in 15 under conditions developed by Schoenebeck and co-workers gave 29 [57]. Bromodegermanylation using NBS employing conditions from Schoenebeck gave bromotriazoles 30 and 31 in moderate to excellent yield [62]. These could then undergo Suzuki–Miyaura cross

• -coupling to give 32 or chemoselective Negishi coupling to give 33 [74]. Finally, BPin 21 could be oxidised to the phenol derivative 34 or cross-coupled with piperidine under Chan–Lam conditions to give the aniline derivative 35 in good yield [75]. Conclusion In summary, we have developed a general method

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• and Suzuki–Miyaura cross-coupling reactions followed by Brønsted acid-mediated cycloisomerisation. The developed methodology tolerates various functional groups and leads to moderate up to quantitative yields of the final products. The impact of different functional groups on the optical properties

• known which allow for an individual introduction of substituents at both positions [37][38][51][52][53][54][55][56][57][58][59][60][61]. In our previous work, we developed a new method which enables both positions to be independently functionalised by Sonogashira- and Suzuki–Miyaura cross-coupling

• of palladium-catalysed Sonogashira–Hagihara and Suzuki–Miyaura cross-coupling reactions (Scheme 1). The final cyclisation step is accomplished by an acid-mediated cycloisomerisation. The synthesis of starting materials 4 was carried out by our previously reported protocol [65]. While compounds 4a–f

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorovinyl ethers, which contains a reactive bromine atom, to afford a series of fluoroalkenes and fluoroenynes in moderate to high yields. Keywords: fluoroalkenes; fluoroenynes; multihalogenated vinyl ethers; Suzuki–Miyaura cross-coupling reactions; Sonogashira cross-coupling reactions; Introduction

• First, we optimized the conditions of the Suzuki–Miyaura cross-coupling in reference to the report by Yang et al. (Table 1) [43]. Upon the treatment of multihalogenated vinyl ether 1a with phenylboronic acid 4a (1.3 equiv) and palladium diacetate (10 mol %) as a catalyst at 40 °C, Suzuki–Miyaura cross

• % yield (Table 1, entry 13). Thus, it was concluded that triphenylphosphine is necessary for Suzuki–Miyaura cross-coupling of 1 with 4 and that it is involved in the production of palladium(0). Next, the reaction conditions for the Sonogashira cross-coupling were optimized (Table 2). On the basis of a

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• ML and automated robotic experimentation to accelerate the exploration of general reaction conditions for heteroaryl Suzuki–Miyaura cross-coupling. They achieved an average yield that was twice as high as that of previous human-guided experiments. Recently, Wang et al. [65] formulated the

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• Suzuki coupling of β,β-dibromenones 100, boronic acids, and 1,1-dimethylhydrazine in a three-component reaction (Scheme 36) [119]. The intermediary 5-bromopyrazoles formed by condensation/N-demethylation/cyclization sequence subsequently react by Suzuki–Miyaura cross-coupling in a one-pot fashion. The

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• synthetic strategy leading to pyridones bearing different aryl substituents is described in Scheme 2. During the Suzuki–Miyaura cross-coupling reaction, which introduced the substituents in the C-5 position, the methyl ester protection of the amino acid moiety was also cleaved, leading directly to the final

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• obtained. Compounds 3a–j were subsequently transformed to 5a–t by Suzuki–Miyaura cross-coupling. The bromination of 1 was performed by using Br2 (1 equiv), Ac2O (1.5 equiv), AcOH (25 °C, 1 h) and yielded the desired product in 52% [62]. With the starting material in hand, initial Sonogashira–Hagihara cross

• carried out by application of the Suzuki–Miyaura cross-coupling. The optimization was carried out with 3a as the model compound (Table 1). The starting material 3a is a sterically hindered system in which the bromine is only partially accessible, due to the large residue. This could be the reason for the

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• corresponding boronic acid 9 and a Suzuki–Miyaura cross-coupling between 8 and 9 gave rise to dimer 10, followed by the oxidation of both acenaphthene units into 1,8-naphthalic anhydrides. Installation of the thiepine ring was achieved by a double nucleophilic aromatic substitution induced by sodium sulfide

• corresponding bis(thiophenyl) thioether, which then underwent successive bromination and iodination to give intermediate 18. Next, a two-fold Suzuki–Miyaura cross-coupling occurring chemoselectively on the iodinated positions allowed the symmetric extension of the hydrocarbon scaffold, with the insertion of two

• thiepine via a two-fold Suzuki–Miyaura cross-coupling with 1,2-phenylenediboronic pinacol ester. The resulting S-doped extended tribenzothiepine 21 proved stable under ambient conditions for several months and exhibited good solubility in common organic solvents, which is ascribed to the boat-shape

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• ]azepine and tetrabromothiophene-S,S-dioxide, followed by oxidative aromatization in the presence DDQ to afford compound 25 in an overall 75% yield. Suzuki−Miyaura cross-coupling reaction of compound 25 with (4-ethylphenyl)boronic acid in the presence of Pd(CH3CN)2Cl2, SPhos, and K3PO4 then furnished the

• benzo[b]naphtho[2,3-f]oxepine 66 with tetrabromothiophene-S,S-dioxide in toluene followed by oxidative aromatization in the presence of DDQ afforded tetrabrominated aromatics 67 in an 81% yield. Subsequently, fourfold Suzuki–Miyaura cross-coupling of polybrominated compound 67 was performed, affording

• nanographenes 96 and 100 using helicene or oxa-helicene as the linkers, respectively [56]. The first π-extension started from the borylated penta-tert-butyl HBC 92. The chemical selective Suzuki−Miyaura cross-coupling reaction between 92 and 93 followed by Scholl oxidation produced compound 94 in an overall 50

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• [34], dibromodithienothiophene 24 is lithiated with n-butyllithium at −90 °C, and the resulting species is reacted in situ with triisopropyl borate. After aqueous workup, dithieno[3,2-b:2’,3’-d]thiophene-2,6-diylboronic acid (25) is obtained, enabling subsequent Suzuki–Miyaura cross-coupling [36

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• ]. Additionally, halotryptophans were incorporated in pentapeptides as building blocks for macrocyclisation by Suzuki–Miyaura cross-coupling (SMC) aiming at the preparation of bicyclic peptides [71]. Recently, intramolecular SMC has been successfully applied to side chain-to-tail cyclisation between

• –Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to

• –Miyaura cross-coupling; Introduction Peptide cyclisation emerged as a popular approach to limit conformational mobility in order to enhance the binding affinity towards a biological target. Moreover, cyclic peptides are more stable against proteolytic digestion and can provide an improved membrane

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• 43 Prague 2, Czech Republic 10.3762/bjoc.17.179 Abstract The stereoselective Suzuki–Miyaura cross-coupling of (Z)-β-enamido triflates is demonstrated. Depending on the nature of the ligand in the palladium catalyst, either retention or inversion of the configuration during the synthesis of β,β

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• /bjoc.17.162 Abstract A facile synthesis of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridine derivatives is reported which is based on POCl3-mediated cyclodehydration followed by double Suzuki–Miyaura cross-coupling. The absorption and fluorescence properties of the obtained products were investigated and

• 3,5-dibromoanthranilic acid (1) [61] with cyclohexanone in POCl3 through an adapted reported procedure [62] (Scheme 1). With precursor 2 in hand, we intended to expand the π-conjugation of the tetrahydroacridine core by adding diversely substituted aryl groups using the Suzuki–Miyaura cross-coupling

• transmetalation. The use of dioxane instead of toluene (Table 1, entry 11) gave again a very good yield (89%). However, the employment of THF resulted in a decreased yield (Table 1, entry 10). The best result for the Suzuki–Miyaura cross-coupling between 2 and 3a was obtained using 1 mol % of Pd(PPh3)4 and 4

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

• –Miyaura cross-coupling reaction of a variety of halogenated methoxybenzene-containing compounds with 2-(formylphenyl)boronic acids in generally good yields [15]. As a next step, the biaryl aldehydes 13a–f were converted into their corresponding oximes 14a–f in good yields as a mixture of (E) and (Z

• substituents in a range of positions. In all cases at least one methoxy substituent was positioned ortho- to the biaryl axis. The other aromatic ring had to contain an oxime ester, which would form an iminyl electron donor, as shown in Scheme 2. As illustrated substrates 13a–f were accessed using the Suzuki

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• −Miyaura cross-coupling produced a series of 5-aryl-4-ethynyl triazoles 136 in the presence of Pd(PPh3)4 as catalyst and K3PO4 as base in 1,4-dioxane as solvent at 100 °C (Scheme 39) [62]. A paper by Sekar et al. described the synthesis of polycyclic triazoles 142 through a domino alkyne insertion and C–H

• 134 were used as starting material in the Sonogashira and Suzuki reactions. The Sonogashira−Hagihara cross-coupling led to alkynylation at position 5 of the triazole ring in the presence of CuI and Pd(PPh3)4 as catalytic system as well as K3PO4 as base in THF as solvent at 65 °C. However, the Suzuki

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• be inspected from Scheme 7, our journey in this regard stem from the iodination of 2 using H5IO6/I2/H2SO4 in acetic acid–water solvent system to afford the desired triiodotruxene derivative 22 in 50% yield. Furthermore, Suzuki–Miyaura cross-coupling reaction of 22 with 4-formylphenylboronic acid (23

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• Suzuki–Miyaura cross-coupling reaction of bromosumanene 82 under microwave reaction conditions. Whereas another route involves the Ni-catalyzed aryl–aryl homo-coupling between the two molecules of iodosumanene 79 [51][52]. Moreover, the bissumanenyl 92, which is thought to be chiral because of the two

• , very few reports could be found for selective functionalization at the peripheral carbons because of difficulties arose during their synthesis. In this regard, Toda et al. in 2017 have successfully synthesized 2,3,5,6,8,9-hexaarylsumanene derivatives 95a–h utilizing a Suzuki–Miyaura cross-coupling

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• group hinder the electrophilic modification at the 3-position. Generally, the aryl group is introduced by a Suzuki–Miyaura cross-coupling reaction [4][5], for which 3-bromo-4-nitrophenol must be prepared by the nitration of 3-bromophenol [6][7]. An alternative approach is the nitration of 3-arylphenol

Suzuki–Miyaura cross coupling is not an informative reaction to demonstrate the performance of new solvents

• James Sherwood

Beilstein J. Org. Chem. 2020, 16, 1001–1005, doi:10.3762/bjoc.16.89

• , equilibria, solubility, and ultimately product yield. If there is an observable change in reaction performance correlating to one or more solvent properties (often polarity), then it is possible to identify and implement an optimum solvent. Suzuki–Miyaura cross coupling is the premier method of palladium

• applicable) of Suzuki–Miyaura cross couplings [8]. Despite this, the reaction is generally tolerant of a wide range of solvents (often an ether or amide solvent is used, and water is a common co-solvent). This calls into question the benefits of using Suzuki–Miyaura cross coupling as a test of new solvents

• , regardless of how vital the reaction is. Three variations of the Suzuki–Miyaura cross-coupling protocol were performed. Each case study is a transformation of phenylboronic acid (1.2 molar equivalents) under different conditions (see Scheme 1), but all using 1 part water to 3 parts organic solvent (by volume

Direct borylation of terrylene and quaterrylene

• Haruka Kano,
• Keiji Uehara,
• Kyohei Matsuo,
• Hironobu Hayashi,
• Hiroko Yamada and
• Naoki Aratani

Beilstein J. Org. Chem. 2020, 16, 621–627, doi:10.3762/bjoc.16.58

• hinderance of Bpin moieties. Finally, to demonstrate the utility of the borylated oligorylenes, the Suzuki–Miyaura cross-coupling reaction of TB4 under the standard conditions was performed (Scheme 3). Coupling of TB4 and 2-bromomesitylene with Pd(PPh3)4, Cs2CO3 and CsF in a mixture of toluene/DMF furnished

• -dioxaborolan-2-yl. Synthesis of 2,5,12,15-tetrakis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quaterrylene (QB4): (a) (Bpin)2 (12 equiv), [Ir(OMe)cod]2 (20 mol %), di-tert-butylbipyridyl (40 mol %), 1,4-dioxane, at 105 °C, 38 h, yield 0.4%. Suzuki–Miyaura cross-coupling reaction of TB4 with 2-bromomesitylene

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

• reaction, followed by dehydrogenative photocyclization, and FeCl3-mediated oxidative cyclization (Scheme 2a) [43]. Tao, Chao, and co-workers succeeded in the preparation of similar tetrasubstituted tetrabenzocoronenes by a Corey–Fuchs reaction, followed by a Suzuki–Miyaura cross-coupling, and a two-step

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• , numerous methods for the synthesis of these compounds have been developed, examples are the Pechmann condensation [10][11], Stille coupling reaction [12], Knoevenagel condensation [13], Heck coupling reaction [14], Kostanecki reaction, Baylis–Hillman reaction [15], Michael reaction [16], Suzuki–Miyaura

• cross-coupling reaction [17], Negishi cross-coupling reaction [18] and Wittig reaction [17]. The concept of the incorporation of fluorine into organic molecules has gained much interest since Fried and Sabo reported the improvement of the therapeutic index of cortisol by the incorporation of a fluorine

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• , Québec, QC, G1V 4G2, Canada Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany 10.3762/bjoc.15.276 Abstract A two-step palladium-catalyzed procedure based on Suzuki–Miyaura cross coupling, followed by a double Buchwald–Hartwig reaction, allows