Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• substitution/addition reactions became the standard for end-capping reactions, although a transition metal–catalyzed cross-coupling reaction has also been used to synthesize CD-based rotaxane. Typically, water-soluble components are prepared, after which the Suzuki coupling reaction in water is used to

• α-CD-based rotaxane comprising a stilbene axle that was synthesized by the Suzuki coupling reaction to light irradiation (Figure 6, right) [58]. In this structure, α-CD was first located on the trans-stilbene moiety, after which it moved to the benzene ring moiety via the cis-isomerization of the

• into the polymer system, further modification and structural analyses were performed [48][74]. The axle end was easily modified by bromination of the benzene ring and successive transition metal–catalyzed cross-coupling reaction, such as Suzuki or Sonogashira coupling (Figure 10A). Furthermore, the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• -unsaturated esters 143 and TBHP to afford α-peroxy-γ-diketones 145 was also disclosed under the catalysis of dirhodium(II) complex Rh2(esp)2 (esp = α,α,α′,α′-tetramethyl-1,3-benzenedipropanoate) (Scheme 45c) [109]. A three-component radical coupling reaction has been established for the assembly of β

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• -naphthols 21 by using iodonium salts 16 as the source of the aryl group (Scheme 7) [61]. Through optimization, it was determined that the presence of Na2CO3 as base and cyclohexane as solvent facilitated the C–C cross-coupling reaction. The products were obtained in satisfactory yields using various

• . Notably, the efficiency of the cross-coupling reaction was observed to increase with the transfer of electron-poor aryl groups from the hypervalent iodine salt. Thus, electron-withdrawing substituents such as trifluoromethyl, m-chloro, and fluorine on the aryl group promoted efficient coupling. Moreover

• 62. Acetonitrile was identified as a suitable solvent for this reaction, resulting in moderate to good yields of the products. The three main steps in the reaction were oxidation of the aryl iodide, addition of the TMP auxiliary, and C–O coupling reaction. Olofsson et al. worked towards the synthesis

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

• porphyrins [34] and tetrabromoanthracenyl porphyrins [35]. In general, the halogen atom needed for the Suzuki coupling reaction resides on the porphyrin; however, Suzuki–Miyaura reactivity has also been shown to be reversed whereby the synthesis of borolanylporphyrins leads to a different approach to

• Discussion Investigation of the Suzuki coupling reaction at the meso-phenyl position of dodecasubstituted porphyrins Synthesis of porphyrin precursors To investigate the Suzuki coupling at the ortho-, meta- and para-position of a dodecasubstituted saddle-shaped porphyrin, first the precursor porphyrins 11

• literature procedure [35]. With initial success in the synthesis porphyrin 26, this Suzuki coupling reaction was performed on 13, for a range of boronic acids/esters as shown in Figure 2 and Scheme 2. Boronic acids/esters were chosen based on their electronic properties (activating/deactivating) as well as

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• fluoride ion, respectively. Volcanic 1.3.3, a Python package for the NaviCat platform, was used to generate 3D volcano plots, facilitating the identification of the most appropriate catalyst for the coupling reaction being considered [27]. Volcano plots Volcano plots are a visualisation of the Sabatier

• ), S1 is the substituent on the LB, and S2 is the substituent on the LA. Capture of CO2 and PO by an FLP Chemoselectivity Our investigations began by examining the uncatalysed coupling reaction between CO2 and PO (Scheme 1), which exhibits a calculated activation barrier (ΔG‡) greater than 55 kcal·mol−1

• chosen to avoid addressing asymmetry concerns at this stage. The capture exhibiting the lowest activation barrier was considered the first step of the coupling reaction for the remainder of the study. The free-energy profiles of both capture processes are depicted in Figure S1 (Supporting Information

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• )–H functionalization C–N coupling reaction by developing an electrochemical method for the bioconjugation of tyrosine in proteins/polypeptides with phenothiazine residues, achieving excellent site- and chemoselectivity (Scheme 4a). This method was inspired by an earlier work from the Gouin group

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• Information File 1 for details) [43]. As expected, amides 5 also undergo tandem diazotization/azo coupling reaction to form the target [1,2,5]oxadiazolo[3,4-d][1,2,3]triazin-7(6H)-ones 7. It should also be noted, that compounds 7 were obtained in similar yields as the corresponding furoxan analogues

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• generates a stannylated imidoyl radical 20. The subsequent 5-exo cyclization, hydrogen abstraction from n-Bu3SnH, and aromatization successfully afforded the stannylated indole derivative 21 (Scheme 13) [8][54][55][56]. The stannyl group of 21 could be transferred to aryl or vinyl group by cross-coupling

• reaction. At the same time, Bachi et al. succeeded in synthesizing a 5-membered nitrogen-containing heterocycle based on the 5-exo cyclization of isocyanides with alkenyl or alkynyl groups using thiols as mediators (Scheme 14) [57]. The generated thiyl radical attacks the isocyano group and forms imidoyl

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

• one-pot process (Scheme 43) [140]. This alkynone generation fulfills two functions: on the one hand, it acts as an activating reagent in the coupling reaction and, on the other, as a ring-forming component. Notably, this process can only be carried out as a domino reaction. For the coupling of

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• , Alcazar et al. developed continuous flow protocols for both the generation of alkylzinc halides and for the subsequent Negishi cross-coupling reaction [40][41][42][43][44]. We successfully adapted Alcazar’s protocols for the synthesis of otherwise challenging heteroaryl–alkyl connections (see Table S1 in

• decarboxylation during the hydrolysis step. Compounds 6j, 6l and 6r passed validation in moderate to good yields (Scheme 8). Conclusion In conclusion, by taking advantage of the recent advances in the Negishi cross-coupling reaction we obtained a broad range of heteroarylacetates starting from heteroaromatic

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

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• bifunctional amide nucleophiles (Scheme 1e). Results and Discussion Our studies here focused on the development of hypervalent iodine-catalyzed amide and alkene coupling reaction [53][54][55]. In this case, we started with styrene (1) and benzamide (2) as the standard substrates. Using iodotoluene A as the

• 8% of the oxazoline product 3 (Table 1, entry 13). These reactions validated the critical roles of each individual component to achieve an efficient reaction. To understand this coupling reaction better, we have also performed time studies to elucidate the effects of several key features in this

• position and subsequent cyclization will furnish the desired oxazoline. Conclusion We have developed a hypervalent iodine-catalyzed amide and alkene coupling reaction. This reaction protocol furnished useful oxazoline products and introduced the use of lithium salts to activate hypervalent iodine catalysts

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• radical and silane furnishes a Si-based radical, which in turn reacts with the thiocarbonate to form an alkyl radical. Finally, a coupling reaction of the alkyl radical with (bpy)Cu(III)(CF3)3 leads to the formation of the trifluoromethylation product and a Cu(I) species. Oxalates: In 2015, Macmillan and

• success of the reaction. The reaction was well compatible with various N-phthalimidoyl oxalates (i.e., 31h–k) as well as electron-deficient alkenes (i.e., 31l–o). Xanthates: In 2017, Molander and co-workers [51] introduced a C(sp3)–C(sp2) cross-coupling reaction of benzyl radicals generated from o-benzyl

• the thiyl radical by [Ir(II)] generates a thiolate anion and [Ir(III)]. Finally, the thiolate anion is converted to the aryl thiol via proton transfer to complete the catalytic cycle. In 2021, MacMillan and co-workers [55] introduced a cross-coupling reaction of alcohols with aryl halides through

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• 10.3762/bjoc.20.118 Abstract A novel Rh-catalyzed one-pot homo-coupling reaction of aryl Grignard reagents was achieved. The reaction with bromobenzenes having an electron-donating group or a halogen substituent gave the corresponding homo-coupling products in good yields, although the reaction using

• for integrins which is critical for several diseases. Keywords: biphenyltetracarboxylic acid; homo-coupling; integrin inhibitor; rhodium catalyst; Ullmann-type reaction; Introduction The Ullmann reaction is a coupling reaction of aryl halides using copper, traditionally using metallic copper-bronze

• benign synthetic applications [14][15][16][17][18]. We have successfully achieved various reactions using a Rh complex easily derived from dialkylzinc (R2Zn) and RhCl(PPh3)3 [19][20]. Additionally, in the related study, we also reported a new Rh-catalyzed C(sp3)–C(sp3) homo-coupling reaction of benzyl

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

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• carbon monoxide insertion, and Suzuki–Miyaura coupling reaction, from 2-gem-dibromovinylaniline [12]. In the presence of Pd(PPh3)4 (5 mol %) as catalyst, 5 equivalents of base (K2CO3), an aryl- or heteroarylboronic ester (1.1 equivalents), CO (12 bar), in dioxane at 100 °C after 16 h the indole

• indoles Metal-catalyzed cyclocarbonylative coupling reaction of indoles to 6H-isoindolo[2,1-a]indol-6-one scaffolds Substituted 6H-isoindolo[2,1-a]indol-6-ones are important structural components of many naturally occurring and pharmacologically active compounds [45][46][47][48][49][50][51]. They are also

• , the Li’s group and Zeng and Alper developed two different methods for carrying out a direct carbonylation of indoles with alkynes. Li’s group reported the direct Sonogashira carbonylation coupling reaction of indoles and alkynes catalyzed by Pd/CuI in the presence of iodine as oxidant [71]. The

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• NMM (8 equiv) in DMF. Each Fmoc deprotection step of the peptide N-terminus was conducted by the repeated treatment of the peptide on resin with 20% piperidine in DMF (2 × 10 min). After each coupling reaction, the resin was washed with DMF. Synthesis of C60–peptide conjugates 5a–c The synthetic

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• co-workers reported that the combination of NHPI esters and cesium carbonate (Cs2CO3) gave rise to a new absorption band in the visible region, suggesting the formation of a photoactive charge-transfer complex [70]. This activation mode was initially employed in a decarboxylative coupling reaction

• the three-component alkylacylation of olefins [108]. Alternatively, NHC catalysts can mediate the generation of radical intermediates from NHPI esters via the stabilization of a photoactive EDA complex. In 2020, Wang and Chen reported a photochemical C(sp3)-heteroatom coupling reaction of NHPI esters

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• mixture underwent a cross-coupling reaction with prenyl monophosphates [46] in DMF/THF over a four-day period, yielding fully protected versions of lipid II and its analogues. Subsequent global deprotection reactions, using aqueous NaOH, led to the formation of lipid II (11), with an overall yield of 16

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• approaches resulted in shortening the synthetic routes that were widely employed to access these heterocyclic scaffolds. Over the last decades, the Chan–Lam coupling reaction has drawn great attention among the synthetic chemistry community which contributed to the development of various synthetic routes to

• via a cross-coupling reaction with NH3 [13]. The reaction was undertaken in the presence of a catalytic amount of a palladium catalyst and afforded a library of dibenzodiazepinones in good to excellent yields (Scheme 1a). In 2013, Zhang et al. developed a synthetic route leading to structurally

• , the desired intermediate 3a was obtained in 20% yield along with 55% of the phenazine 6 (entry 14, Table 2). Although toluene was shown to be a good solvent for this B–H coupling reaction, we were unable to prevent the double B–H reaction from occurring leading to the phenazine 6, even when shortening

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• a subsequent Glaser–Hay coupling reaction, a RA acceptor unit was introduced to provide a DTF-IF-RA donor–acceptor scaffold with a low-energy charge-transfer absorption and multi-redox behavior. Keywords: alkynes; chromophores; fused-ring systems; heterocycles; redox chemistry; Introduction

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• the synthesis of compound 81 through the utilization of the Negishi cross-coupling reaction and then the removal of TMS groups from this intermediate was achieved using TBAF, resulting in the formation of diyne 82 in 65% yield. The progression towards the synthesis of biphenylene-containing substrate

• selectively synthesize compound 87 through a hybrid approach involving the integration of both solution and surface chemistry techniques [53]. The key compound 96 to be used in the synthesis of POA 87 was synthesized in two steps. In the first step, 94 was obtained using a double Sonogashira cross-coupling

• reaction, followed by a Au(I)-catalyzed [4 + 2] cycloaddition reaction to afford the target substrate 96 and its regioisomer 95 in a 2:1 ratio (Scheme 20). POA 87 was obtained on Au(111) at 610 K after Ullmann-type coupling and aromatic dehydrogenation of compound 96. Apart from these studies, the

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• derivatives followed by the radical coupling reaction is more plausible for the formation of the corresponding adducts rather than the SN2 reaction mechanism of the La@C2v-C82 anion with benzyl bromide derivatives. Conclusion The reaction of La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C

Thienothiophene-based organic light-emitting diode: synthesis, photophysical properties and application

• Recep Isci and
• Turan Ozturk

Beilstein J. Org. Chem. 2023, 19, 1849–1857, doi:10.3762/bjoc.19.137

• 4-bromo-N,N-diphenylaniline (5) with n-butyllithium at −78 °C and addition of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. The Suzuki-coupling reaction of TT 4 with borolane 6 produced the intermediate 7 in 81% yield. The target D–π–A-type fluorophore, DMB-TT-TPA (8), was produced by

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• -mediated domino reaction of chromone-3-carboxaldehydes and amines [41], Pd-catalyzed redox-neutral C–N coupling reaction of iminoquinones with electron-deficient alkenes [42], NH3 insertion into o‑haloarylynones [43], gold(III)-catalyzed azide-yne cyclization [44], Michael/Truce-Smiles rearrangement