Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• reaction to rapidly establish the tetracyclic skeleton of complanadine A and an iridium-catalyzed site-selective pyridine C–H borylation followed by a Suzuki–Miyaura cross coupling to forge the C2–C3’ linkage. Their synthesis achieves a high degree of synergy between classic transformations and modern

• lycodine 34 underwent Ir-catalyzed C3–H borylation mainly guided by steric factors to provide boronic ester 35 in 75% yield. With the boronic ester handle at the C3 position, the subsequent Suzuki–Miyaura cross coupling between 35 and 33 occurred smoothly to deliver pseudo-dimer 36, which upon acidic

• -oxidation at one of the two benzylic positions, they started with benzylic oxidation of 34 using SeO2 to provide 37, which was further oxidized to pyridine N-oxide 38. Treatment of 38 with POCl3 in DMF delivered 2-chloropyridine 39 for the subsequent Suzuki–Miyaura cross coupling with 35 to form the C2–C3

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• hydroxyketone 104 in excellent diastereoselectivity and enantioselectivity [9][11]. Ozonolysis of the double bond in 104 followed by Purdie methylation with Ag2O/MeI, base-mediated vinyl triflation, and Pd-catalyzed Suzuki–Miyaura cross coupling with pinacol boronate 105 delivered diene 106. Next, The Et2AlCl

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• –B [14] (Scheme 3E) bonds. In the case of an asymmetric cross-coupling reaction (Scheme 3C) [10], both sets of the substituents on individual aryl groups are considered because neither is involved in the bond formation/cleavage. Accordingly, the catalyst-controlled atroposelective Suzuki–Miyaura

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• propargylsilane 7d halogenation–cyclization cascade and Suzuki–Miyaura cross-coupling in the second step [22]. Thus, we have developed a faster and palladium-free route towards tetrahydrofurans 8. The latter can still be modified further through silicon–halide exchange followed by cross-coupling chemistry as

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• with 99% ee. The TBS protection was crucial to prevent the potential racemization by intramolecular transesterification. Ester 79 was then prepared from 78 in eight steps. To complete the dimerization, fragments 80 and 81 were independently prepared from 79. An intermolecular Suzuki–Miyaura coupling

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• hybrid decamer 3 in a previous report [26], via a Suzuki–Miyaura cross-coupling reaction between dibromo precursor 1 and borylated precursor 2 (Scheme 1). The resulting mixture was successfully separated by column chromatography on silica using CH2Cl2/n-hexane as an eluent to give icosamer 4 in 6% yield

• common organic solvents. Conclusion A novel o-phenylene-pyrrole-thiophene hybrid macrocycle (icosamer 4) was synthesized via Suzuki–Miyaura cross-coupling and isolated in 6% yield. Oxidation of 4 with PIFA produced a partially fused aza[5]helicene-containing macrocycle 5 in 58% yield, which was also

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• , Howell et al. recently disclosed a general method for the synthesis of 2-halomethylideneoxetanes through halogenation of 2-methylideneoxetanes using N-halosuccinimides, and illustrated their synthetic utility by Suzuki–Miyaura, Sonogashira and Buchwald–Hartwig coupling reactions [53]. In addition to Cu

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• accordance with coupling constants and resulting dihedral angles. Keywords: conformational restraints; dihedral angle NMR; half-chair conformation; modified amino acids; pipecolic acid; stereoselective hydrogenation; Suzuki–Miyaura cross-coupling; Introduction Non-proteinogenic amino acids play an

• structure of pipecolic acid is rather challenging and often necessitates early-stage derivatization followed by the formation of the six-membered ring [29][30][31][32]. An alternative is to utilise derivatization reactions such as Suzuki–Miyaura [33] or Sonogashira–Hagihara [34] cross-coupling reactions on

• a key intermediate product. This late-stage approach was previously described by us while utilising Suzuki–Miyaura or Sonogashira–Hagihara cross-coupling reactions to generate pipecolic acid derivatives with alkynyl substituents in the C6 position [35]. Here, we present a robust synthetic route to

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• -dechlorination product was observed. This notable result suggests performing a second coupling using conventional chemical methods, such as the Suzuki–Miyaura reaction. Furthermore, the coupling yield decreased for phenyl bromides bearing bulky ortho-substituents while hydrodehalogenation byproducts formed. The

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• of 74% for bromine 2 and 78% for iodo starting material 3 (Table 3) [24]. To overcome the problems of poor yields in the arylation of N-acetyl diazocines via Stille coupling we used Suzuki–Miyaura reactions of the diazocines 2 and 3 with different arylboronic acids [25][26]. There are several

• examples of last-step modifications of azobenzenes via Suzuki–Miyaura reactions in the current literature, which indicate that the reaction conditions are compatible with azo groups [27][28]. Suzuki–Miyaura reaction of 2 and 3 with different phenylboronic acids resulted in the formation of the

• with bis(pinacolato)diboron did not lead to the formation of the pinacolborane-substituted N-acetyl diazocine 18. Accordingly, the Suzuki–Miyaura reaction with inversed roles between N-acetyl diazocine boronic acid pinacol ester and aryl or alkyl halides could not be investigated. The Buchwald–Hartwig

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• of stereoselective Suzuki–Miyaura couplings, offering precise control over both categorical and continuous variables (Figure 2a) [15]. The integrated robotic system containing a four-needle dispense head facilitated the delivery of reagents in low volume and slurries, ensuring the accuracy and

• selection, a dispensing module for solids and liquids, a reaction module capable of heating and stirring, a sample preparation module, and a LC–MS characterization module (Figure 2d). The efficiency of the system has been demonstrated in three reactions types, namely Suzuki–Miyaura coupling, Buchwald

• drug molecules autonomously, and it does not include a closed-loop optimization framework. The Pfizer research team developed a custom-designed flow system for rapid reaction screening of the Suzuki–Miyaura coupling reaction on a nanomolar scale [50]. The platform included a modified HPLC system that

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

• boronic esters of 1,8-DHN have recently been investigated and reported by Krempner and co-workers [51]. To our delight, the Suzuki–Miyaura coupling/intramolecular C–H arylation sequence between 12 and boronic ester 17d proceeded smoothly affording product 15a in 84% yield. The results summarized in Table

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

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• porphyrin architectures, which could be used in supramolecular assemblies, catalysis, or sensing. In this work a library of arm-extended dodecasubstituted porphyrins was synthesized through the optimization of the classic Suzuki–Miyaura coupling of peripheral haloaryl substituents with a range of boronic

• further substitution directly on the meso- or a meso-phenyl ortho/meta/para positions of a porphyrin, is the introduction of C–C bond forming chemistry. This is typically achieved using palladium and/or another transition-metal catalyst [20]. Sonagashira [21], Suzuki–Miyaura [22], Heck [23], Stille [24

• coupling reactions, Suzuki–Miyaura couplings are known to be a robust tool when functionalizing porphyrins [29][30]. Many complex porphyrinoid architectures have been synthesized in this manner, from functional porphyrin arrays [31][32][33] to sterically challenging meso-substituted aryl bis-pocket

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

• fluoroenynes via Suzuki–Miyaura and Sonogashira cross-coupling reactions using novel multihalogenated fluorovinyl ethers, which are easily prepared from the reaction between phenols and 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane). These reactions make use of the unique structure of multihalogenated

• 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

• chlorine atoms as reported by Hosoya and Niwa et al. In this study, we investigated the synthesis of fluoroalkenes 2 or fluoroenynes 3 by Suzuki–Miyaura or Sonogashira cross-couplings with a key building block 1 (Scheme 1D). Results and Discussion Optimization of the conditions of cross-coupling reactions

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

• simply memorize the most frequently reported solvents and reagents in the literature. Beker et al. [178] showed that some machine learning models could not outperform simple statistical analyses based on the popularity of reported conditions in the literature, using the Suzuki–Miyaura coupling as an

• 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

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• catalysts’. While the concept of generality was recently explored in a closed-loop fashion for Suzuki–Miyaura cross couplings to find the most general catalyst and reaction conditions [131], the application of this concept in the context of ML has found comparatively less attention in organocatalysis

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

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• -di(het)aryl groups via Suzuki–Miyaura [26][27][28] or Sonogashira [29][30][31] reactions. In this study, we report a straightforward method to obtain a diverse array of N-substituted DPP derivatives through a two-step process. Firstly, the N-alkylation of Pigment Red 254 (DPP 1) is achieved using

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

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• Suzuki–Miyaura coupling with boronic ester 53 and O-acetylation furnished 54. The dienophile component, morachalcone A (44), was synthesized from phenol 55 in four steps including O-prenylation and subsequent Claisen rearrangement, aldol condensation with 56, and deprotection. The key chemo-enzymatic

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• achieved with one-pot Suzuki–Miyaura coupling to arrange phenylene rings and pyridinylene rings in an alternating fashion. Analyses with UV–vis spectroscopy showed changes in the photophysical properties with nitrogen doping, and X-ray crystallographic analyses experimentally revealed the presence of

• were installed in an outward-radiated manner, which expands the structural diversity to exploit the chemistry at the periphery of [n]CMP (Figure 1b). Through the use of Suzuki–Miyaura coupling for macrocyclisation, pyridinyl and phenylene rings were assembled in an alternating fashion, which afforded

• -doped [n]CMPs, 3a and 3b, were synthesized via one-pot Suzuki–Miyaura coupling [12] (Scheme 1). Previously, we synthesized [n]CMPs with inward-focused nitrogen dopants by using Suzuki–Miyaura coupling with Pd(PPh3)4 as the catalyst [13] and applied this method to outward-radiated congeners in this work

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