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

• reactions occurred under mild conditions and without any need of transition-metal catalysts. In 2023, Wu and colleagues successfully synthesized a range of meta-substituted biaryl ethers. The reaction involves phenols 61 and cyclic diaryliodonium salts 73, dissolved in tert-butyl alcohol, in the presence of

• group of the iodonium salt was also investigated. A potential radical-mediated mechanism was evaluated. Under mild conditions, a base-promoted arylation of general sulfinates 86 without the need for transition metals was introduced using diaryliodonium salts 16 as an aryl source (Scheme 35). Inspired by

• 101 for the S-arylation of potassium O-alkyl xanthates 100 offers a simpler approach [95]. This method operates under mild conditions, facilitating the creation of substituted S-aryl xanthates 102 (Scheme 41). Utilizing diaryliodonium salts for the arylation of xanthate anions provides a pathway for

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

• transformed into a series of useful molecules, enabling them an important backbone in organic synthesis. Lin et al. [66] used sodium sulfinates as the nucleophiles to realize the asymmetric sulfonylation of yne-allylic esters. The reaction can be carried out under mild conditions with good to excellent regio

• spiroannulation of 2-naphthols or electron-enriched phenols under mild conditions with excellent regioselectivities, enantioselectivities and diastereoselectivities (Scheme 44, 43a–g, 44a–q). In addition, the nucleophilic substitution–dearomative cyclization process between indoles and yne-allylic esters can also

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• aromatic substitution giving the final spiro-indolenine. The scope of the process has been investigated with respect to all three components. Simple operations, mild conditions, and good yields make this strategy a convenient and sustainable way to obtain novel spiro-indolenine derivatives. Keywords

• spiro-heterocyclic indolenines from readily available starting materials under mild conditions and in a diversity-oriented fashion remains desirable. In this contest, oxidative isocyanide-based multicomponent reactions (oxidative IMCRs) can be considered as a convenient tool [15]. Actually, the use of

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• , Trombay, Mumbai-400085, India Homi Bhabha National Institute, Anushaktinagar, Mumbai, PIN-400094, India 10.3762/bjoc.20.223 Abstract A transition-metal-free decarbonylation–oxidation protocol for the conversion of 3-arylbenzofuran-2(3H)-ones to 2-hydroxybenzophenones under mild conditions has been

• to scale-up due to their violent reactions at elevated temperatures. Our protocol involved mild conditions, and to our expectations, a gram-scale conversion of 3ba to 4ba proceeded smoothly without appreciable loss in the reaction yield (Scheme 3). The reduced reaction time and a lower reaction

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

•  1c). This method could be carried out without any special apparatus, and the mild conditions led to the wide range of applications. Results and Discussion Initially, we used triphenylbismuthine (1a) and bis(pinacolato)diboron (2) as the model substrates to optimize the reaction conditions (Table 1

• air under mild conditions. Therefore, many triarylbismuthines could be used to form a variety of useful arylboronates in moderate to good yields with excellent product selectivity. We hope that this new approach to the generation of aryl radicals from triarylbismuthines will lead to an increased use

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

• direct activation of C(sp3)–H bonds under mild conditions [17]. The pronounced electron-deficient W2C nanocatalysts greatly facilitate the direct deprotonation process, ensuring the longevity of the electrode by overcoming self-oxidation. The LSF of drug molecules such as ibuprofen methyl ester and

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

• a carboxy group using carbon dioxide as carboxy source is generally difficult under neutral and mild conditions without the use of metal catalysts and/or ligands. This protocol represents a novel method for synthesizing diarylacetic acids 2 from the corresponding alcohols 1 in one step by using an

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

• proved ineffective in facilitating the Michael addition of bisthiomalonates to conjugated ketones, whereas DABCO enabled the formation of desired products under mild conditions [30]. However, reports of highly stereoselective protocols utilizing hydrogen bonding catalysis have mainly focused on

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

• ], and crosslinked polymers [14][15][16][17]. Since crosslinking polymers requires high reaction efficiency under mild conditions, developing such reactions is crucial. We previously reported the regioselective double azide addition to octadehydrodibenzo[12]annulene with hexyloxy substituents (DBA-OHex

• -withdrawing groups was successfully synthesized. This molecule underwent SpAAC with two equivalents of benzyl azide under mild conditions to quantitatively form the regioselective symmetric bistriazole product. The electron-withdrawing substituents facilitated the reaction progress as compared to the

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

• intramolecular addition of enamine I to the C3=O to form intermediate II, which dehydrates to cyclic carbinol III. Finally, dehydration of intermediate III yields anilines 3. Conclusion In summary, a method for the synthesis of substituted meta-hetarylanilines under mild conditions starting from 1,3-diketones

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

• ). Since this 1,2-shift reaction proceeds under mild conditions and in the absence of a radical initiator, it is thought to proceed by an ionic rather than a radical mechanism. Alkoxy and cyclopropyl radicals, which are more reactive than the usual alkyl radicals, are capable of abstracting hydrogen from

• -membered cyclic diboron compounds 18 undergo an insertion reaction of isocyanides into the boron–boron single bond of 18 under mild conditions without the addition of any additives (Scheme 11a) [48]. The reaction is thought to proceed by an ionic mechanism. Recently, several insertion-type reactions of

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

• predominates over saponification under our mild conditions (room temperature). Overall, the reaction proceeds smoothly without any unwanted side reactions such as saponification of the ester groups. Having optimized the reaction conditions, we proceeded to examine the substrate scope of the developed

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

• conducted under remarkably mild conditions. Results and Discussion The initial step of our method involved the N-alkylation of DPP 1 with pentafluorobenzyl bromide (Scheme 1). Although a similar reaction had been previously reported for other DPP derivatives, the experimental conditions used (DMF, K2CO3

• excellent nucleophiles and generally react under mild conditions, resulting in the substitution of the 4-F atom of the pentafluorophenyl groups. In this case, reactions with thiols were performed in dry DMF and K2CO3 was used as the base. Three different thiols were tested: pyridine-4-thiol, pyridine-2

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

• -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

• the ortho-pyridine-substituted diarylamines. The oxidation can be performed either chemically, using bis(trifluoroacetoxy)iodobenzene as the oxidant, or electrochemically, via potentiostatic oxidation. The electrochemical synthesis occurs under mild conditions; no chemical reagents are required except

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• converted into the corresponding acids 4a,b by hydrogenolysis under mild conditions, which proceeded in quantitative yields (Scheme 4). It should be noted that this method of preparing β-lactam acids compares favorably with the alkaline hydrolysis of their methyl and ethyl esters, which does not always give

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

• mild conditions (10% SDS in water at rt with no added catalyst) [16]. Recently, the GBB reaction has also benefited from the use of inorganic nanocomposites and macromolecules, as demonstrated by the contributions of Rostamnia and Jung. Rostamnia et al. intercalated, by ion exchange technique, Ni

• derivatization, allowed the obtainment of 18 in high yield under relatively mild conditions, and was extended to the synthesis of 23 analogues, all in high yields (>86%). The catalyst could be recovered from the reaction medium by precipitation and reused up to five times without loss in activity. In 2020, Tyagi

• using 30 equiv of AcOH in DMA, with no damage of DNA observed. The GBB reaction, under these mild conditions, demonstrated a wide range of scope. Different aldehydes were tested: benzaldehydes with different substituents, heteroaromatic and bicyclic aromatic aldehydes, all giving good results. Only

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• sodium hydride, yielding moderate yields (ranging from 23% to 68%). The cyclization initially formed the non-isolated intermediate i, which was oxidized by molecular oxygen from air, introducing the hydroxy group at the α-position of the cyano group. The protocol utilised mild conditions and short

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

• synthesized 33 generated the highly reactive intermediate 34 in aqueous solvents under mild conditions [37][42]. In this process, the co-solvent (cs) allowed control of the dimerization modes via either Michael addition or Diels–Alder reactions, facilitating the systematic total synthesis of the

• approach, they used a chiral boron catalyst as a Lewis acid and achieved at best an endo/exo selectivity of 1.9:1 in a similar DA reaction. The use of Diels–Alderase in their recent work significantly improved the endo/exo selectivity under mild conditions in water, thereby highlighting the strengths of

• this problem, the research group designed synthetic substrate analogs (96, 101) that mimic the biosynthetic intermediate 88 (Scheme 10A). By replacing an amide linkage in 88 with an ester linkage, the fatty acid side chain could be removed under mild conditions after enzymatic construction of the

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• straightforward conditions (Scheme 1). The synthesis of aryl halides is of great academic and industrial importance. Recently, our research group has developed a new procedure for the ortho-selective chlorination of phenols under mild conditions in a short reaction time [26]. The chlorinating species was

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• compounds with the PEM-type reactor. The chemoselective reduction of nitrogen-containing compounds under mild conditions is important for organic synthesis, and we believe that the PEM reaction system is a powerful tool that can be applied to a wide variety of nitrogen-containing compounds. Schematic of (a

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• and will hopefully encourage further development in key areas. This is particularly pertinent to the late-stage benzylic fluorination of complex molecules, which will require exceptionally mild conditions in order to tolerate a broad range of functional groups. A) Benzylic fluorides in bioactive

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• Cu(III) center [49][50][51]. Conclusion In summary, we have developed an efficient and practical protocol for the synthesis of alkylnitriles directly from readily available aliphatic carboxylic acids. The reaction proceeds under mild conditions and exhibits exceptional substrate generality and

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• undergo cyclization reactions under mild conditions. In case of 1,3-diphenylacetone (4a) some activation of the methylene group is observed as well, because of benzylic stabilization. Dianions of 1,3-dicarbonyl compounds follow a different regioselectivity as compared to simple monoanions [6][7][8][9][10

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• methanol was achieved at 100 °C with one equivalent of t-BuOK. In all the cases, the catalytic system selectively yielded mono-N-alkylated and N-methylated products under mild conditions. Noteworthy, high functional group tolerance, such as alkenes, halogens, thioethers, and benzodioxane derivatives was

• % of Mn4 and 1.1–1.5 equiv of t-BuOK in 1,4-dioxane at 120 °C for 20 h, affording good to excellent yields of the substituted pyrimidines (Scheme 68). The same group disclosed an efficient synthesis of substituted pyrroles from aminoalcohols and secondary alcohols using Mn4 under mild conditions [95

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• group of compounds 7 should be protected prior to the attempted isoxazole ring formation. Indeed, reactions of 7a–c with ethylene glycol gave dioxolane derivatives 9a–c which were converted into isoxazolo[4,5-b]pyridines 10a–c in high yields under mild conditions (Scheme 4). The obtained result prompted

• ). All other compounds 12 bearing no electron-withdrawing groups in the aryl moiety readily afforded the corresponding triazole derivatives in high yields under relatively mild conditions (K2CO3, DMF, 60 °C, Scheme 5). Substituents in the pyridine ring did not affect this transformation thus indicating