Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• different electronic properties (18, 25–41, Figure 6) were screened as catalysts for the sulfa-Michael addition of tert-butyl benzylmercaptan 42 to phenyl vinyl sulfone (43). Without the addition of a porphyrin, no product was formed. Among the non-alkylated porphyrins (18, 25–32) only the ones containing

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

• a major content of the material, Takata and co-workers developed the rotaxane crosslinker, which can be integrated as a small content on vinyl polymer synthesis to afford vinyl polymers having a certain domain of polyrotaxane crosslinking points (Figure 14) [84]. In this system, the crosslinker was

• synthesized and exhibited a rotaxane crosslinking nature; hence, the resulting vinyl polymer, e.g., polyDMAAm crosslinked by VSC, showed enhanced stretchability induced by rotaxane crosslinking. Moreover, when it was applied to a thermo-responsive polymer like poly(N-isopropyl acrylamide) (NIPAM), the thermo

• -responsive nature became much faster than the system without VSC. This fast responsiveness was induced by the dynamic rotaxane crosslinking structure. This method can be applied in various vinyl polymer systems, and induces the rotaxane crosslinking nature to the resulting network polymer, suggesting its

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• configuration of the double bond was confirmed using 1H,1H-NOESY spectroscopy. As shown in Figure 2, a correlation between protons of the allyl moiety and the aryl substituent evidenced their spatial proximity in molecule 1c. The absence of a correlation between allyl and vinyl protons additionally supported

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

• , C–C bond formation was reported by Chen and colleagues in 2020 via the arylation of vinyl pinacol boronates 23 by using diaryliodonium salts 16 to yield trans-arylvinylboronates 24 in the absence of a metal catalyst [62]. The optimized reaction conditions involve the reaction of substituted

• diaryliodonium salts 16 with different substituted vinyl pinacol boronates 23 in dichloromethane as solvent at 100 °C in a sealed tube in the presence of a wet inorganic base (Scheme 8). Both K2CO3 and Li2CO3 were found to be compatible with the reaction, and it was observed that no product was obtained in the

• , including di- and trisubstituted ones, were well tolerated in the reaction, providing products 24 with good stereoselectivity in moderate to good yields. Moreover, the reaction was successfully conducted with various substituted vinyl pinacol boronates and di(4-tolyl)iodonium triflate, resulting in moderate

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• phenacyl group, yielding 9 without any detectable cyclization product (Scheme 4). This hydration process is thought to proceed via two paths. The reaction is initiated by the protonation of the ethynyl group to generate the vinyl cation intermediate 10. Product 9 is directly formed by the attack of a water

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• expand the scope of transition metal-catalyzed substitution reactions. Since its discovery in 2022, copper-catalyzed yne-allylic substitution has undergone rapid development and significant progress has been made using the key copper vinyl allenylidene intermediates. This review summarizes the

• developments and illustrates the influences of copper salt, ligand, and substitution pattern of the substrate on the regioselectivity and stereoselectivity. Keywords: copper-catalysis; copper vinyl allenylidene intermediate; 1,3-enyne; 1,4-enyne; yne-allylic substitution; Introduction Copper is earth

• substitution has emerged as a new and robust approach to achieve formal allylic substitution using stabilized nucleophiles. The copper acetylide-bonded allylic cation with copper vinyl allenylidene species as its resonance structure is key for the process, which can achieve the outer-sphere attack of

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

• development of a dual-reactive fluorine-containing C2-unit, which was prepared from trifluoroethanol in two steps in 63% yield, allowed the convergent synthesis of fluoroalkenes (Scheme 1C) [26]. We recently found multihalogenated vinyl ethers 1 could be obtained by the reaction of phenols with 2-bromo-2

• 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

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

• agrochemical and pharmaceutical chemistry. In 2019, Jiao and colleagues reported that 1,2-dichloroethane (DCE) could be used as a chlorination reagent for the production of (hetero)aryl chlorides and vinyl chlorides [21]. The reactions were carried out in an undivided cell containing a mixture of DCE in

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• excellent enantioselectivities (89–98% ee) and low to moderate yields (48–72%). The homologation step proceeds via the stereoretentive 1,2-migration of the vinyl group from the tetracoordinated boron to the highly electrophilic carbon of the diazomethane, concerted with the elimination of the nitrogen

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• observed when AQ-3 was applied. Besides, the modifications of the quinuclidine ring through replacing the vinyl substituent in the parent quinine core by a triple bond (AQ-5) led to no substantial improvement in the mixer mill, but the decrease of enantioselectivity in the reaction performed in the

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• the use of HF or its complexes as a reagent. These reactions seem to proceed via the formation of the vinyl fluoride as the intermediate [25][26][27][28]. In the first example, Olah and co-workers reported the reaction of terminal alkynes with HF/pyridine (Olah reagent) (Figure 1, reaction 1) [29][30

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• the strain-promoted double azide addition feature, DBA 5 was evaluated as a crosslinker for azidated polymers. After 5 (5 mol %) was added to a partially azidated poly(vinyl chloride) (PVC-N3) (x = 0.11, n = 1000) in THF, the solvent was gradually evaporated on a Teflon boat. The resulting self

• metal-free click reaction was employed to crosslink a partially azidated poly(vinyl chloride). The crosslinking proceeded by simply mixing the polymer and crosslinker in THF and evaporating, and the formation of the crosslinked polymer film was confirmed by the strain–stress curves. The developed method

• partially azidated poly(vinyl chloride) (PVA-N3) was prepared by stirring poly(vinyl chloride) and NaN3 in DMF at room temperature overnight. Measurements NMR spectra were recorded using a JEOL mode Al300 (300 MHz) at room temperature. Deuterated chloroform was used as the solvent unless otherwise stated

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

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

• vinyl ether enables the synthesis of 3-alkoxyalkenones 74, presenting an elegant route. Subsequently, these compounds undergo a three-component reaction with various hydrazines, forming 1,3-substituted pyrazoles 75 (Scheme 26) [104]. However, one limitation is the formation of 1,5-substituted pyrazoles

• pyrazole starting materials from isonitriles 158, dialkyl acetylenedicarboxylate 147, and hydrazine carboxamide 159. The addition of the isonitrile to the Michael system yields a nitrilium-vinyl anion zwitterion 161, that is protonated by the hydrazine carboxamide, which undergoes addition to furnish the

• toluene [173]. N-Vinylimidazole, an alkene with a leaving group, was used to synthesize the 3-substituted pyrazoles 169 because, unlike acetylene, it is not gaseous and, therefore, easier to handle. Instead of vinylimidazole, vinyl azides 170 can also be used as alkyne surrogates. After the 1,3-dipolar

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• reactions, especially as a Michael donor at the central methylene carbon, and Michael acceptor at the enone vinyl carbon. Therefore, it would be interesting to develop novel methodologies using curcumin and its non-natural analogs as key starting materials [24]. Because of its multifaceted reactive site

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• synthesis of 1,2-difluoroethylene based on perfluoropropyl vinyl ether as starting material can be found (Scheme 7). Consequently, two methods to prepare 1,2-difluoroethylene in the laboratory have been described to date. Even though at least five approaches to HFO-1132 can be found in patent literature, it

• -difluoroethylene and the disappearance of vinyl protons resonances in the 1H NMR spectra [78]. Addition to the C=C bond Halogen addition: 1,2-Difluoroethylene was reported to react with chlorine [46][79] and bromine [51] under irradiation, yielding 1,2-difluoro-1,2-dihaloethanes in moderate to high yield (Scheme 9

• silane that was obtained was pyrolyzed to form vinyl fluoride. It was shown that SF5Br easily reacted with the E- and Z-isomer, respectively, of 1,2-difluoroethylene in the presence or absence of light, yielding a mixture of erythro- and threo-isomeric addition products in both cases (Scheme 14) [92

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• heterylidenepyruvic acid. An optimized synthetic protocol for this transformation was elaborated and a plausible sequence involving the elimination of the 2-chloroacetamide moiety and the conversion of the β-chlorovinyl fragment into a vinyl one is provided. Keywords: convertible isocyanides; multicomponent reaction

• of acid also led to the formation of amides 10b–d as main products and the corresponding ketobisamides 12d–e as minor products (Table 2, entries 10, 11, 18, 23, and 24). This can be explained by the formation of HCl in the reaction mixture due to the substitution of chlorine in the vinyl chloride

• conversion of the β-chlorovinyl fragment into a vinyl fragment giving rise to ethyl (E)-4-(4-(R1-amino)-3,4-dioxobut-1-en-1-yl)-3,5-dimethyl-1H-pyrrole-2-carboxylates. Another direction of the post-transformation was the replacement of the chlorine atom in the β-chlorovinyl group of the Ugi bisamides with a

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• detected as a side reaction via mass spectrometry. Vinyl alcohols were also studied, giving carvone (4v) in 74% yield without oxidation of the double bonds. Finally, other heterocyclic benzylic alcohols were investigated, which led to undesired chlorinations in the case of benzimidazoles 3w and 3x and

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

• components, such as various acrylates, α,β-unsaturated acids, enones, enals, acrylamides, vinyl phosphonates, and vinyl sulfones. Various cesium salts of oxalates also performed well using this protocol. Isopropyl and tert-butyl groups present in an adjacent position of oxalates do not disturb the reaction

• molecules and results in a tertiary alkyl radical, which eventually reacts with an alkyne to yield a vinyl radical 35. Later, the addition of Ni(0) and ligand to the vinyl radical 35 gives the intermediate 36. This intermediate undergoes oxidative addition with aryl bromide to produce Ni(III) species 37. A

•  21). Styrenes selectively reacted with vinyl ethers in the presence of an acridinium photocatalyst and a diphenyl disulfide HAT catalyst to produce the aldehyde product when exposed to blue LED light. Differently substituted styrenes were examined using this protocol, which produced the aldehyde

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and

• [15], and the Nazarov reaction [16][17][18][19][20]. The Nazarov cyclization is one of the most versatile and simple methods for preparing indanones from aryl vinyl ketone derivatives [16][17][18][19][20]. The Nazarov reaction is classically formulated as a 4π conrotatory electrocyclization of a

• may drive further structure–activity relationship studies to identify indanone targets of pharmacological interest. Conclusion In summary, we developed a simple and efficient methodology for the Nazarov reaction of aryl vinyl ketones, leading to 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• dichlorophosphane 9 from commercially available PCl3 and ethyl vinyl ether using a previously published procedure [68]. Compound 9 reacted with 1 equiv of benzyl alcohol in absolute Et2O and pyridine at −78 °C, followed by quenching of the reaction mixture with H2O. This procedure provided phosphinate 10 in more

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

• vinyl propargylic esters could be employed as five-carbon atom building blocks in [5 + 2] cycloadditions with alkynes or alkenes by carbene intermediates. Starting from those results they envisaged the benzannulation of heteroaryl propargylic esters favored by CO [44]. The process led to the desired

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• motif in bioactive compounds and the synthetic utility of its olefinic C=C bond. The most extensively explored approach to this transformation is the transition metal-catalyzed C–N coupling between azoles and vinylating agents, including vinyl halides [4], boronates [5], sulfonium salts [6][7][8], and

• between 4ba and 4-methoxybenzenethiol furnished the N,S-substituted olefin 7 in 59% yield. The treatment of 4aa with stoichiometric CuI and ʟ-proline effected the iodine(III)-to-iodine(I) conversion to give the vinyl iodide 8 in 76% yield. Compound 8 was used for the Ullmann coupling with imidazole

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• in moderate to good yields, employing 2,7-dimethoxythioxanthone (2,2’-OMeTX) as a triplet sensitizer for BCB excitation (Scheme 3A) [38]. Starting from BCB 24, alkenes including styrene derivatives, enol ethers, and vinyl boronates could be incorporated to give 1,2-BCHs (±)-25a–d. Brown and co

• alkenes including acrylates, vinyl sulfones, and acrylamides could all be incorporated and the number of accessible bifunctional 1,2-BCHs was increased further by chemical transformation (Scheme 3D) [35]. Among the reported transformations were reduction of the ketone (to (±)-34), hydrolysis of the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• state thereof, denoted with an asterisk, possessing a reduction potential of 2.0 V versus SCE (saturated calomel electrode). Subsequently, this excited state undergoes quenching through photoinduced electron transfer (PET) with styrene 5. The resulting vinyl radical cation exhibits electrophilicity at

• the homobenzylic position, engaging in an anti-Markovnikov manner with a formal chloride nucleophile. The ultimate step involves hydrogen atom transfer (HAT) with thiol 148, culminating in the formation of the desired product 147. Therefore, the generation of the vinyl radical cation plays a pivotal

• role in determining the regioselectivity, with the positive charge being more pronounced on the β-position compared to the α-position. A discussion of the regioselectivity of vinyl cations was already reported in 1973 by Neunteufel and Arnold [91]. They concluded their pioneering paper by stating: “In