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

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• azido-hydration reaction [18]. The homopropargylic azide was obtained in only 28% yield using phenyl vinyl ketone. Based on reported aza-alkynylation reactions [19][20][21][22][23] and modern azidation methods using radical chemistry [17][24][25][26] three approaches could be envisaged. All of them

• with potential for further modification by cross-coupling. The full scope of the transformation can be found in Supporting Information File 1, Schemes S2 and S3 [45]. Concerning scope limitations, the azido-alkynylation of vinyl-pyridine 1b was unsuccessful and thiazole 1c only afforded 18% of the

• solubility in DME, which might cause the low yield observed. Ynonetrifluoroborate 5d could not be introduced as nucleophile, probably due to its reduced reactivity caused by the electron-withdrawing acyl group. Unfortunately, although Molander previously reported the use of vinyl-trifluoroborate 11 to trap

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

• of RAEs with organozinc reagents under Co-catalysis, effecting diverse arylation, alkenylation, and alkynylation reactions [92]. The second type of reaction is referred to as cross-electrophile coupling and involves the Ni-catalyzed reaction of NHPI esters with aryl- and vinyl halides under reducing

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• presence of methyl vinyl ketone (MVK) as a radical acceptor (Table 1). Tetrabutylammonium dibutyl phosphate (phosphate base), which operates as a PCET initiator through hydrogen bond formation with the N–H bond of amide/carbamate [11], was used as an additive. As a result, N-alkylated product 3 was

• electrochemical conditions. Experimental General procedure of anodic oxidation Compound 1 (145 mg, 0.2 mmol), Bu4NPF6 (387 mg, 1 mmol), CH2Cl2 (10 mL), phosphate base (90 mg, 0.2 mmol) and methyl vinyl ketone (32.7 μL, 0.4 mmol) were added to a test tube, which was then subjected to a constant electrical current

• in vacuo and the resulting residue was subjected to 1H NMR spectroscopy or column chromatography. A divided-cell experiment was performed using an H-type cell (4G glass filter). Compound 1 (0.2 mmol), Bu4NPF6 (387 mg, 1 mmol), phosphate base (90 mg, 0.2 mmol), CH2Cl2 (10 mL), and methyl vinyl ketone

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• University of Technology, Stremayrgasse 9, 8010 Graz, Austria 10.3762/bjoc.20.6 Abstract The reactions of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol and various Michael acceptors (acrylonitrile, acrylamide, methyl vinyl ketone, several acrylates, methyl vinyl sulfone) yield the respective phosphonium

• carbanion [13][14]. Also with other Michael acceptors such as methyl vinyl ketone, several acrylates as well as methyl vinyl sulfone the reaction proceeds smoothly under the same reaction conditions (Scheme 1). Conversions of 1 are usually quantitative within 24 h and all phosphonium phenolates can be

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

• /E isomers in approximately 85:15 ratio. The same spectra in CDCl3 showed broad coalescent signals for the characteristic vinyl CH protons, which is indicative of a dynamic equilibrium between the isomers. For both types of nitro intermediates 3 and 6 the final ring-forming step required reduction of

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• -unsaturated phthalimide 33a. Simultaneously, radical III of the catalyst was also formed, accompanied by the extrusion of CO2. Subsequently, the alkyl radical A added to the carbon–carbon triple bond of enynal 32g, resulting in the formation of a vinyl radical intermediate B, followed by a 5-exo-trig

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

• Aaron H. Shoemaker,
• Elizabeth A. Foker,
• Elena P. Uttaro,
• Sarah K. Beitel and
• Daniel R. Griffith

Beilstein J. Org. Chem. 2023, 19, 1615–1619, doi:10.3762/bjoc.19.118

• , entry 2) and Vanderwal [17] (Table 1, entry 3) in the synthesis of other bridged azapolycycles gave poor yields when applied to vinyl bromide 7. The best result was obtained using the combination of Pd(PPh3)4, K2CO3, and proton sponge in refluxing toluene [18][19]. Although this catalyst system proved

• give superior yields for otherwise identical Heck reactions. Thus, iodoamine 11 (Scheme 2b) was synthesized (see Supporting Information File 1) to evaluate this finding in the context of our system. Subjection of 9 to the same conditions that proved optimal for vinyl bromide 7 resulted in the formation

• of the expected product 4, but with essentially no improvement in yield (Table 1, entry 5). Jeffery conditions [16], which have been shown to work well with similar vinyl iodides, provided a very low yield (entry 6 in Table 1). However, we had better success when we adapted the conditions developed

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• late last century. To continue with the discussion on polymer construction, section 2 explores some emergent polymer synthesis techniques via a radical process but other than a chain-growth mechanism by addition of radical species to vinyl monomers. In section 3, we cover radical chemistry approaches

• poly(vinyl chloride) (PVC) [14]. About half of the industrial polymers manufactured worldwide are produced by radical polymerization [15][16]. 1.2.1 Key features of radical polymerization: Radical polymerization, which has a classical chain reaction process, usually analyzed kinetically on the

• advantages are (i) the universality to a wide range of monomers such as (meth)acrylates, (meth)acrylamides, dienes, vinyl ethers/esters, etc.; (ii) tolerance to unprotected functionalities in monomers and the solvent including –OH, –COOH, –SO3H, etc.; (iii) different reaction conditions, including bulk

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• ). Thus, in the 1H NMR spectra, downfield shifts of vinyl protons H2 and H3 upon protonation were 0.50–0.61 and 0.41–0.54 ppm, respectively. In the 13C NMR spectra, ∆δ values for carbons С1 and С3 were 12.7–21.3 and 6.0–13.4 ppm, respectively. The NMR data revealed that the positive charge in the O

• -protonated forms B is substantially delocalized from the carbonyl group to vinyl carbon C3. For fluorophenyl-substituted compounds and cations 1d and Ad, 2d and Bd, also a large downfield shift of the corresponding fluorine signals is observed in the 19F NMR spectra (∆δ = 25.3–25.7 ppm), which shows a

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• site-selective NHC–Cu-catalyzed hydroboration of enantiomerically enriched allenes and conversion to the corresponding β-vinyl ketones demonstrates the importance of the strategy. An example is shown below (Scheme 44). 2.2.4 Reaction with organozinc reagents: Organozinc reagents, such as diethylzinc

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• alkenyl compounds, the vinyl ether function is characterized by a (Z)-configuration as shown in Figure 1. In addition, an acyl group is present on the secondary alcohol of the glycerol. This acyl group is constituted by a saturated or unsaturated lipid chain or, in the case of platelet-activating factor

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• ketones 94 with ethers [81]. Contrary to what was obtained for the alkylation of coumarin at the carbonyl α-position, vinyl ketone undergoes Michael addition and ether addition at the β-position of the carbonyl (Scheme 20). The reaction delivered various alkylation products in good to excellent yields

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• acetaldehyde have been reported [20][21][22][23][24]. The safety and handling problems associated with acetaldehyde can be solved by synthetic equivalents that can be generated in situ through different paths. Some examples are represented by vinyl acetate [25], silyl vinyl ethers [26], ethanol, pyruvic acid

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• hydroarylation of tert-butyl vinylcarbamate and unactivated alkenes like 1-octene and 3-buten-1-ol although the vinyl carbamate substrate (Epred = −2.2 V vs SCE) is significantly easier to reduce than most aryl chlorides. This selectivity, especially considering the need for an excess of the vinyl carbamate

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• carbonyl groups of the urea fragment are observed (Figure 4). Values of spin–spin interaction constants 3JCH equal to 5.3–6.0 Hz indicate the cis-orientation of the vinyl proton and the carbonyl (for 4a, blue) or the carboxyl group (for 5a, red) relative to the double bond [24][25][26]. The values of spin

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• biological activities. Hence, looking at the importance of azaindolines in drug discovery a protocol of rare earth metal-catalyzed intramolecular insertion of the pyridine C–H bond into unactivated vinyl C–H bonds has been developed by Chen and co-workers [108] (Scheme 38). Using this protocol azaindolines

• 205 were accessed in moderate to excellent yields and also naphthyridine derivatives (205k and 205l) were synthesized. In the proposed mechanism, the initial deprotonation of HNBn2 by Ln[N(TMS)2]3 provided the lanthanide amide. Activation of the vinyl-substituted pyridin-3-amine 204 by the lanthanide

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• –elimination. Both they are potential chiral phosphorus ligands (Scheme 20) [25]. When Fuchs and co-workers investigated the conversion of cyclic vinyl sulfones to vinylphosphonates, they found that the reaction of (1S,2R)-2-methyl-3-(phenylsulfonyl)cyclohept-3-en-1-ol (100) and diethyl phosphonate generated

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• developed a Lewis acid-promoted conjugate addition to unreactive Michael acceptors such as amides or vinyl heterocycles [60]. Trimethylsilyl triflate or boron trifluoride-activated unsaturated amides underwent highly efficient and enantioselective addition of Grignard reagents. When this methodology was