The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• Suzuki–Miyaura reaction and then subjected the adduct 52 to a GBB reaction with various aldehydes and isocyanides (Scheme 20) [53]. Focusing on the GBB part, the authors tested both Lewis acids (Sc(OTf)3 or Yb(OTf)3) and Brønsted acids (NH4Cl or AcOH) and found that the best results could be obtained

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• obtain the pure compound that met the requirements (>99.5%) [41]. Another very recent report which couples a Suzuki–Miyaura reaction with inline purification, uses capture-SMB technology as its purification approach [42] (Table 2, entry 2). The crude material is directed into two twin C-18 columns that

• reported by Pitts and collaborators. This study achieves full removal of metal species after common homogenous catalytic reactions such as a Suzuki–Miyaura reaction, Sonogashira reaction or hydrogenation mediated by Wilkinson’s catalyst [84]. Other interesting examples to remove transition metals in

• successfully coupled to a Suzuki–Miyaura reaction [119]. Crystallization was identified as a suitable purification technique to separate products from unreacted starting materials while avoiding metal contamination. Water was used as antisolvent and two mixing units were needed in the crystallization process

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• Suzuki–Miyaura reaction [35]. It should be noted that the inverse coupling, i.e., of 2-bromonorbornadiene with arylboronic acid derivatives is also a reasonable and already tested alternative route, that gives very good yields in the case of higher substituted norbornadiene products [28][29]. However

Synthesis of novel multifunctional carbazole-based molecules and their thermal, electrochemical and optical properties

• Nuray Altinolcek,
• Ahmet Battal,
• Mustafa Tavasli,
• William J. Peveler,
• Holly A. Yu and
• Peter J. Skabara

Beilstein J. Org. Chem. 2020, 16, 1066–1074, doi:10.3762/bjoc.16.93

• potassium acetate (KOAc) and dichlorobis(triphenylphosphine)palladium(II) in 1,4-dioxane [36][37]. Upon chromatography (9-hexylcarbazole-3-yl)boronic acid pinacol ester (5) was obtained as a liquid in good yield. (9-Hexylcarbazole-3-yl)boronic acid pinacol ester (5) was subjected to Suzuki–Miyaura reaction

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

• conventional solvents. In this work, the suitability of the Suzuki–Miyaura reaction to demonstrate the usefulness of new solvents was evaluated, including Cyrene™, dimethyl isosorbide, ethyl lactate, 2-methyltetrahydrofuran (2-MeTHF), propylene carbonate, and γ-valerolactone (GVL). It was found that the cross

• coupling is often unaffected by the choice of solvent, and therefore the Suzuki–Miyaura reaction provides limited information regarding the usefulness of any particular solvent for organic synthesis. Keywords: cross coupling; green solvents; palladium; solvent selection; Suzuki reaction; Findings The

• from a green chemistry perspective if the water can be reused. To this end, micellar chemistry is appropriate for cross couplings [19]. Residual water also assists ‘solvent-free’ methods [20]. In summary, the Suzuki–Miyaura reaction is a fantastically versatile and industrially important reaction [21

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

• results were rationalized based on docking studies. Keywords: Buchwald–Hartwig reaction; cyclization; N-heterocycles; palladium; Suzuki–Miyaura reaction; Introduction Furoindoles and their derivatives have received a lot of attention based on their versatile pharmaceutical activities. Furoindols were

• ten benzo[4,5]furo[3,2-b]indole derivatives based on regioselective Suzuki–Miyaura reaction of 2,3-dibromobenzofuran with 2-bromophenylboronic acid and subsequent cyclization. The difference between the work of Truong and our approach mainly lies in the synthesis of the cyclization precursor. The

• literature procedure, 2,3-dibromobenzofuran (1) was synthesized by bromination of benzofuran [33]. The Suzuki–Miyaura reaction of 1 with 2-bromophenylboronic acid (2), carried out under standard conditions using Pd(PPh3)4, afforded the desired product 3 in 84% yield and with very good regioselectivity. The

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• palladium-catalysed reactions (Scheme 38). The first one is a Sonogashira coupling reaction between the terminal alkyne of propiolamide 128 and aryl iodide 129, which is preferred to the Suzuki–Miyaura reaction between aryl iodide 129 and boronic acid 130 present in the reaction mixture. Then, an internal

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• . With the linear peptidyl resin 4 in hand, we investigated its cyclization by means of an intramolecular Suzuki–Miyaura reaction. Thus, based on our previous results on the synthesis of biaryl cyclic peptides [22], 4 was treated with Pd2(dba)3 (0.2 equiv), P(o-tolyl)3 (0.4 equiv) and KF (4 equiv) in

• spectrometry analysis showed that the pNB group was removed under the Suzuki–Miyaura reaction conditions. To obtain the biaryl bicyclic peptide 1, the Boc group of cyclic peptidyl resin 5 was then removed under mild conditions using trimethylsilyl triflate (TMSOTf) in presence of 2,6-lutidine in CH2Cl2 (Scheme

• )-βAla-Glu(Rink-MBHA)-OpNB (7), followed by microwave-assisted intramolecular Suzuki–Miyaura reaction, Boc group removal, and final macrolactamization. Boc-Tyr(3-B(OH)2,Me)-OH was prepared in solution through Miyaura borylation of Boc-Tyr(3-I,Me)-OMe [31], followed by hydrolysis of the pinacolate and

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• the examples shown in Scheme 14 [33]. Nonaflate PM54 underwent a Suzuki–Miyaura reaction to PM55 or a Sonogashira coupling to PM56 under standard conditions. The ethynyl-substituted pyrimidine derivative PM12 could also be employed in C–C coupling reactions as shown by its connection to pyridyl

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• and 5e furnishes piperazin-1-ylchromene 12 in 64% yield. Furthermore, as highly methylated flavonoid derivatives [47] and 6-(3,5-dimethoxyphenyl)chromenes [48][49] have been demonstrated to be potent anti-seizure drugs and anticancer agents, respectively, a Suzuki–Miyaura reaction was performed

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• selectivity using a differently ortho-substituted phenylbornic acid was observed. Keywords: arylpyridines; atropisomerism; cross-coupling; palladium; Suzuki–Miyaura reaction; Introduction Axially chiral biaryls not only subsist in many classes of natural and bioactive compounds [1][2] but also are an

• of 3,4,5-tribromo-2,6-dimethylpyridine with 2-methoxyphenylboronic acid under Suzuki–Miyaura reaction conditions gave the mixture of three atropisomeric stereoisomers of 3,4,5-tri-(2-methoxyphenyl)-2,6-dimethylpyridines which were separated by column chromatography and characterized by NMR

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• ] between the benzo[b]quinolizinium-9-trifluoroborate (3b) and aryldiazonium salts. We focused our attention on derivatives 1a–d because in these cases a direct comparison with the already reported synthesis with a Suzuki–Miyaura reaction is possible. As we are particularly interested in benzo[b

• conditions by the Pd-catalyzed Suzuki–Miyaura reaction of the aryldiazonium salts 4a–d with benzo[b]quinolizinium-9-trifluoroborate (3b). The latter substrate was obtained as analytically pure product in moderate yield by the reaction of benzo[b]quinolizinium-9-boronic acid (3a) [34] with NaBF4 (Scheme 1

• -arylbenzo[b]quinolizinium derivatives 1a–d were available in yields that are comparable, or even slightly higher, than the ones obtained with the Suzuki–Miyaura reaction of benzo[b]quinolizinium-9-boronic acid (3a) with bromoarenes [34]. In our previous attempts to synthesize the corresponding benzo[b

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• solvents in the presence of an excess of base [1][2][3]. With the drive for the development of environmentally friendly and low cost protocols, a number of methodologies for the Suzuki–Miyaura reaction under aqueous conditions or in neat water have been reported [4][5][6]. This has been achieved via

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• , Pd-catalysed C–C cross-coupling reactions have become indispensable in many modern synthetic protocols both in the laboratory and on an industrial scale. A highly important representative of this class of transformation is the Suzuki–Miyaura reaction [5][6], involving the coupling of aryl halides

• for catalysts rich in tin. Suzuki–Miyaura coupling reactions Batch reactions The catalytic activity of the synthesised catalysts in the Suzuki–Miyaura reaction was investigated using phenylboronic acid 3 in combination with various bromoarenes 4a–e, featuring ortho- and para-substitution of electron

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• , reversed-phase chromatography was chosen to simplify the purifications. The N-triflylbenzamide group also proved stable to cross-coupling reaction conditions, as exemplified by a palladium-catalyzed Suzuki–Miyaura reaction of the 4-bromo-substituted derivative 9d (Scheme 3). The corresponding N,N’-bis

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• , respectively. Commercially available 4-(N,N-dimethylamino)phenylboronic, 4-methoxyphenylboronic, and 2-thienylboronic acids completed with tributyl(5-methoxythiophen-2-yl)stannane, prepared from 2-methoxythiophene [33], were used. Chromophore 4a was also attempted by Suzuki–Miyaura reaction using the

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• ambipolar materials (CZBDF, Figure 1c) [16]. To note, synthetic functionalization under transition-metal-catalyzed conditions allows the preparation of multi-substituted benzofurans in a facile manner [23][24][25][26][27][28]. Langer et al. reported the site-selective Suzuki–Miyaura reaction of 2,3

Scope and limitations of a DMF bio-alternative within Sonogashira cross-coupling and Cacchi-type annulation

• Kirsty L. Wilson,
• Alan R. Kennedy,
• Jane Murray,
• Ben Greatrex,
• Craig Jamieson and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2016, 12, 2005–2011, doi:10.3762/bjoc.12.187

• . Keywords: Cacchi annulation; cross-coupling; heterocycles; Sonogashira; sustainable solvent; Introduction The Sonogashira reaction [1][2] (Scheme 1) is a robust and broadly applicable Pd-catalysed bond-forming process that, alongside the Suzuki–Miyaura reaction [3], has steadily become an indispensible

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• . achieved a total yield of 70% [11], however, their procedure relies on a Wolff–Kishner reduction of the corresponding acylpyrrole with hydrazine hydrate, making it impractical in countries where the use of hydrazine has been restricted by law [12]. As an alternative, the Suzuki–Miyaura reaction can be

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

• proportions in this work. We preferred to use a 1:1 ratio in the Suzuki–Miyaura reaction as there was not much difference between the obtained results when the ratios used were 3:1 or 1:1. To optimize the reaction conditions, a series of experiments with different bases such as KOH, NaOH and K2CO3 were

• manner. The Suzuki–Miyaura reaction was carried out using electron-rich (4-chloroanisole, 4-chlorotoluene), electron-poor (4-chloroacetophenone, 4-chloronitrobenzene) and electron-neutral (chlorobenzene) substrates. We studied the catalytic activity of compound 1 regarding C–C bond coupling of 4

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

• precatalysts for the Suzuki–Miyaura reaction. Even though allyl and indenyl ligands are similar to cyclopentadienyl (Cp) ligands, there have been no detailed comparative studies exploring the activity of precatalysts of the type (η5-Cp)Pd(L)(Cl) for Suzuki–Miyaura reactions. Here, we compare the catalytic

• . As part of this work the Cp supported Pd(I) dimer (μ-Cp)(μ-Cl)Pd2(IPr)2 (CpDim) was synthesized and crystallographically characterized. It does not readily disproportionate to form monoligated Pd(0) and consequently CpDim is a poor catalyst for the Suzuki–Miyaura reaction. Keywords: cross-coupling

• ; homogeneous catalysis; NHC ligands; palladium; Suzuki–Miyaura reaction; Introduction The Suzuki–Miyaura reaction is a powerful synthetic method for forming C–C bonds between aryl halides or pseudo halides and organoborane containing species [1][2][3][4][5]. The most active catalysts are generally based on Pd

Half-sandwich nickel(II) complexes bearing 1,3-di(cycloalkyl)imidazol-2-ylidene ligands

• Johnathon Yau,
• Kaarel E. Hunt,
• Laura McDougall,
• Alan R. Kennedy and
• David J. Nelson

Beilstein J. Org. Chem. 2015, 11, 2171–2178, doi:10.3762/bjoc.11.235

• [NiCl(Cp)(IMes)] (2). Synthesis of [NiCl(Cp)(ICy)] using conventional heating. Synthesis of (a) [NiCl(Cp)(ICy)] (3) and (b) [NiCl(Cp)(IDD)] (4) with microwave heating. Model Suzuki–Miyaura reaction for the evaluation of the new complexes as cross-coupling pre-catalysts. Experimental data for single

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

• Pd-catalyzed Suzuki–Miyaura reaction. The C–H bond activation process was believed to be initiated by the oxidation effect of the Cu(II) catalyst to give intermediate 54 which was further oxidized to provide cation intermediate 55. The deprotection of 55 gave finally the halogenated products 52

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

• C–H borylation of several 1-substituted-3-(pentafluorosulfanyl)benzenes and applied the products of borylation to the Pd-catalyzed Suzuki–Miyaura reaction with aryl bromides or iodides. However, the reaction is limited to borylations in position five of 1-substituted-3-(pentafluorosulfanyl)benzenes

• [72]. Straightforward access to SF5-phenylboronic acids or boronates would be highly desirable since it would allow easy installation of the SF5-phenyl group by the subsequent Suzuki–Miyaura reaction. Nitro-(pentafluorosulfanyl)benzenes are the primary industrial SF5-aromatics, therefore the easiest

• 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

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