HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• ]. In contrast, the protocol reported herein provides 94–98% yield when employing longer chain-containing aldehydes (1c–e). In addition to resorcinol, 2-methylresorcinol is commonly used in resorcin[n]arene synthesis as radical oxidation of the methyl unit in the ArCH3 fragments provides a benzyl

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• functionalization of amides with alkenes under photoredox conditions. Another viable approach for amide functionalization through photoredox catalysis involves the nucleophilic addition, in the presence of base, of an amide to a radical cation obtained by oxidation of an unfunctionalized alkene moiety (Figure 1A

• ) [23][24][25]. The nucleophilic attack of the nitrogen atom on the oxidized C=C double bond results in the formation of a radical intermediate after deprotonation. This radical intermediate can proceed through various pathways (e.g., HAT, oxidation) to yield the desired final product. In the

• functionalization of amides with alkenes under oxidative conditions, the oxidation potential of the alkene plays a pivotal role in the oxidation to a radical cation through photoredox catalysis [26]. Alkenes that are less functionalized possess a higher oxidation potential, necessitating the use of potent

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• ]. Iodoethane was also shown to be an effective reagent furnishing the product in up to 56% upon heating to 40 °C (Table 1, entries 11 and 12). It was envisaged that oxidation of iodoethane led to formation of oxidized forms of iodide by C–I-bond cleavage, therefore tetrabutylammonium iodide was utilized to see

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• detection of benzaldehyde which was considered to be formed by the NaClO-mediated oxidation of benzyl alcohol generated by hydrolysis. Changing the oxidizing reagent to crystalline NaClO·5H2O nicely solved the problem with the realization of 86% isolated yield of 2b by the utilization of this oxidant (2

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• is produced in situ from the imidoyl chloride 9 [21]. The one-pot oxidation and ring-closure reaction [22][23] to iodoloisoxazolium(III) salt 7OTf and the salt metathesis with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBArF24) were then realized with 85% and 72% yield, respectively

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• (Table 1, entry 6). In contrast, zinc was not effective as an anode material in the carboxylation, probably due to competitive electrochemical reduction of zinc ions generated by electrochemical oxidation of the zinc anode. The deposition of a black precipitate was observed visually at the cathode (Table

• competitively occurs at the cathode, and an excess amount of electricity should therefore be necessary to obtain acceptable results. At the anode, on the other hand, dissolution of magnesium ions by electrochemical oxidation of magnesium metal occurs, preventing electrochemical oxidation of the product and

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• the electrochemical properties of functionalized catechols allows one to suggest the mechanism of their electrooxidation, establish electron transfer centers, and predict antioxidant activity based on electrochemical data. To determine electron-transfer centers, the oxidation potentials of the

• observed in the range of 0.94–1.25 V. It refers to the oxidation of the catechol moiety to the corresponding o-benzoquinone, as previously shown for related compounds [36]. The second redox transition at 1.55–1.84 V characterizes the oxidation of the sulfide fragment (Scheme 2). To confirm the

• participation of the catechol group in the first redox transition, the microelectrolysis of 3 was carried out at a controlled potential of 1.35 V in MeCN (2 h, 0.8 F/mol). After electrolysis, a decrease in the current intensity of the first oxidation peak is observed on the CVs of this compound (conversion

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

• 24, which supported the hypotheses regarding the selectivity-determining transition states arrangement. It is important to note, that boronic acids 14 are highly sensitive to oxidation by air and could only be purified in air-free conditions and stored in airtight containers. Additionally

• generated from Togni’s reagent (145) to a double bond of the δ-alkenylamine, followed by intramolecular hydrogen atom transfer and a single-electron oxidation of the intermediate alkyl radical to form an imine that is then reduced by hydrogen donor 147 catalysed by CPA (R)-VAPOL (148). The

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

• reagent detects nitrite formed by the enzymatic oxidation of NO) [44][45]. As shown in Figure 3, compounds 1a–e containing an aryl substituent at position 6 exhibited low NO-donor ability (0.3–4.5%). In contrast, compounds 1f–h with an aliphatic fragment showed moderate activity, with the maximum value

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

• ), Koser’s reagent (PhI(OH)OTs), Zhdankin’s reagent (C6H4(o-COO)IN3, ABX), and Dess–Martin periodinane (DMP) – and find application in an array of synthetically important transformations including olefin difunctionalization, carbonyl desaturation, alcohol oxidation, and C–H functionalization [3][4

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• sites where benzylic C–H bonds readily undergo metabolism driven by cytochrome P450 oxidases via single-electron oxidation [24]. This metabolic lability may be tempered by hydrogen replacement with deuterium, an almost perfect bio-isosteric replacement (C–H to C–D) which maintains 3D surface, shape and

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

• University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan 10.3762/bjoc.20.194 Abstract gem-Difluorination of carbon–carbon triple bonds was conducted using Brønsted acids, such as Tf2NH and TfOH, combined with Bu4NBF4 as the fluorine source. The electrochemical oxidation of a Bu4NBF4/CH2Cl2 solution

• solution of Bu4NBF4/CH2Cl2 containing substrates might also promote the same reactions (Figure 1, reaction 6, electrochemical method). Currently, electrochemistry can be regarded as a promising technique in organic synthesis, because heavy-metal reagents can be avoided for the oxidation or reduction of

• −’’ equivalents might serve as good reagents for the gem-difluorination of alkynes. Thus, we have examined the electrochemical oxidation of a solution of Bu4NBF4/CH2Cl2 containing 1a (0.5 mmol) in a divided cell using 8 mA or 16 mA (Scheme 1, method B, in-cell method). In-cell method means that EGA was generated

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

• oxidation-controlled cyclooctyne-1,2-quinone cycloaddition (SPOCQ) was developed and employed in the same fields of chemical biology [6][7]. On the other hand, the use of the SpAAC in materials science was slow. We developed another class of metal-free click chemistry reactions, such as the [2 + 2

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ) [25] or β-keto esters (Scheme 1a, path 4) [26][27], the aldol reaction between aldehydes and S-ethyl acetothioate followed by oxidation with Dess–Martin periodinane (Scheme 1a, path 5) [28], the hydrolysis of α-oxo ketene dithioacetals (Scheme 1a, path 6) [29] and MgBr2·OEt2-catalyzed acylation of

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• there are many reasons for this renewed interest, two major motivations are the unmatched control of oxidation or reduction potential that can be achieved and the environmentally friendly aspect of having electrons as the only consumed reagent. This latter reason is certainly an advantage in many cases

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• ) substituent in the meta-position [38][39][40][41][42][43]. For example, several methods based on the Michael condensation–oxidation sequence starting from α,β-unsaturated ketones have been described (Scheme 1B) [44][45][46][47][48][49][50]. Recently, several methods have been developed based on the

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

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

• irradiation (Scheme 23) [81]. After these pioneering reports mentioned above, many examples of cyclization of 2-isocyanobiaryls using a metal-assisted system [82][83][84][85][86], photoredox system [21][87][88][89][90], or some other oxidation systems [91][92][93] were developed as excellent synthetic methods

• in which phosphorus-centered radicals generated from diarylphosphine oxides by Mn(OAc)3-assisted oxidation [94] or the photoredox system [95][96][97] were used in the radical cyclization reaction of 2-isocyanobiaryls (Scheme 24). Yadav and Sigh et al. reported the direct synthesis of 6-sulfonylated

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

• blocks or their transformation with additional components besides hydrazines is a logical entry to MCR syntheses of pyrazoles. Therefore, 1,3-dielectrophiles encompass 1,3-dicarbonyl compounds and α,β-unsaturated carbonyl compounds, including alkenoyl and alkynoyl systems, across various oxidation states

• -unsaturated ketone with hydrazine and acetic acid forms a 1-acylpyrazoline, while the chromene moiety and hydrazine form the pyrazole nucleus by ring opening/ring closing cyclocondensation. Upon oxidation with DDQ, the pyrazolylpyrazoline products can be readily converted into the corresponding bispyrazoles

• -unsaturated cyano derivatives, which in turn can cyclocondense with hydrazines to furnish aminopyrazoles after oxidation. Hasanijedad and Firoozi developed a one-pot process for synthesizing 5-aminopyrazoles 62 in a three-component fashion (Scheme 19) [78]. Interestingly, hydrazine acts both as a Brønsted

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• formation of dimeric side products. Cyclic voltammetry analysis suggested an initial anodic single electron transfer (SET) to radical cation 5, cyclization and deprotonation. Subsequent SET oxidation in solution by 5 led to cation 7. Final deprotonation furnished aromatic cycle 4. In 2022, Zhang et al

• hydrazones initiated with the SET anodic oxidation of the hydrazone and deprotonation to form the N-centered radical 10. After aza-cyclization on the aromatic ring, a second SET oxidation and deprotonation delivered the heterocycle 9. This mechanism was supported by cyclic voltammetry analysis of a model

• substrate (1-(diphenylmethylene)-2-(4-nitrophenyl)hydrazine), which displayed three oxidation peaks (0.9, 1.7 and 2.2 V vs Ag+/Ag in HFIP ). The authors assumed that the two first peaks would correspond to the oxidation of 8 to 10 and 11 to 12 and that the oxidation of 10 would be responsible for the final

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• CH2Cl2 were examined using cyclic voltammetry (Figure 4). Macrocycle 2a exhibited one reversible oxidation wave at 0.44 V and two reversible reduction waves at −0.85 V and −1.14 V. The electrochemical HOMO–LUMO gap of 2a is 1.29 V, which is larger than that of 1a (1.08 V) [2]. DFT calculations We next

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

• , no reaction was observed with indazoles and furans using the first two conditions, requiring the formation of the ketoesters 4j and 4r first, followed by the functional group interconversion (FGI) with NH2OH·HCl (Scheme 6, blue and green sections). The Riley oxidation of the furanyl derivative 2j

• proceeded smoothly yielding 4j in quantitative yield. However, obtaining compound 4r presented some challenges due to the resistance of ester 2r towards conventional oxidation methods (see Table S5 in Supporting Information File 1). Consequently, a multi-step process involving ester hydrolysis and

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• Oleg A. Levitskiy Yuri K. Grishin Tatiana V. Magdesieva Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, 1/3, Moscow, 119234, Russia 10.3762/bjoc.20.166 Abstract A novel facile approach to N-arylpyridoindazolium salts is proposed, based on direct oxidation of the ortho

• -pyridine substituted diarylamines, either using bis(trifluoroacetoxy)iodobenzene as an oxidant, or electrochemically, via potentiostatic oxidation. Electrochemical synthesis occurs under mild conditions; no chemical reagents are required except electric current. Both approaches can be considered as a late

• -stage functionalization; easily available ortho-pyridyl-substituted diarylamines are used as the precursors. Keywords: anodic oxidation; diarylamines; electrochemical cyclization; pyridoindazolium salts; reversible ring closure; Introduction Aromatic polyfused N-heterocycles are of interest as a

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• Sota Adachi Yohei Okada Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan 10.3762/bjoc.20.165 Abstract Electrochemical or photochemical single-electron oxidation of bench-stable substrates can generate radical

• aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes. Keywords: alkene; aza-Wacker cyclization; electrochemistry; radical cation; sulfonamide; Introduction Activating bench-stable substrates is the first

• step to driving bond formation and/or cleavage. Therefore, the discovery of new modes for activation leads to reaction advancements. Electrochemical [1][2][3][4][5] and photochemical [6][7][8][9][10] reactions that induce single-electron reduction and oxidation are widely used in modern synthetic

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• featuring an exocyclic amine (and their substitutions). Systems out of scope of this review are those, where: non-basic ethylamine systems are present (featuring other functionalities due to oxidation states), condensed or polycyclic systems are present and featuring a key amine embedded in a (poly)cycle