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

• iodine as a super-stoichiometric oxidant. The catalyst system has precedent for also facilitating oxygenation reactions [82], which was observed as a competing pathway under these conditions. The catalytic cycle proposed by the authors begins at resting state I (Figure 31), which is generated in situ and

• is subsequently oxidised to Mn(V)-oxo species II by hypervalent iodine oxidant PhIO. This can perform a HAT from the benzylic substrate, in turn generating a benzylic radical and Mn(IV)-hydroxy species III. Ligand exchange with the fluoride source affords complex IV, which performs FAT with the

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• ammonium iodides [40]. Interestingly, designer catalyst C1 was found being catalytically superior compared to Bu4NI (TBAI) when using H2O2 as the oxidant. Furthermore, it turned out that addition of PBN (phenyl N-tert-butylnitrone) has a beneficial effect on the reaction and that carefully buffered

• conditions are best-suited. We have recently established the use of dibenzoyl peroxide (DBPO) as a very powerful oxidant for oxidative heterofunctionalization reactions using simple nucleophilic inorganic salts as heteroatom transfer reagents [39][41]. This was successfully demonstrated for the non-catalyzed

• Bu4NI allowed for the clean and selective formation of 1a, we observed significant amounts of the α-I-ketoester 3 when using KI instead. Having established the combination of DBPO and Bu4NI as the best-suited catalyst/oxidant combination for the α-azidation of 1a using NaN3, we finally optimized

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• alkenes. We previously developed a dihomohalogenation method using selectfluor as an oxidant [27]. Herein, we synthesized bicyclic oxy- and alkoxyfluorine compounds using selectflour as an electrophilic fluorination reagent, water and various alcohols as an nucleophile. Results and Discussion In this

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• oxidant. This metal-free approach was postulated to involve the in situ generation of reactive thio/selenocyanogen chloride (Cl–SCN/SeCN) from the reaction of PhICl2 and NH4SCN/KSeCN, followed by an electrophilic thio/selenocyanation of the pyrazole skeleton. Keywords: PhICl2; pyrazoles; selenocyanation

• oxidant (Scheme 1a–c) [49]. For example, Xu reported that a series of 4-thiocyanated 5-hydroxy-1H-pyrazoles was synthesized by a K2S2O8-promoted direct thiocyanation of pyrazolin-5-ones at room temperature, using NH4SCN as thiocyanogen source (Scheme 1a) [20]. Similarly, utilizing NH4SCN and K2S2O8

• NH4SCN (Table 1, entries 4–6). Next, other oxidants including phenyliodine(III) diacetate (PIDA), phenyliodine(III) bis(trifluoroacetate) (PIFA), iodosobenzene (PhIO), and NCS were applied, and the results indicated that PhICl2 was the most effective oxidant (Table 1, entries 7–10). Later on, when the

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

• hypervalent iodine catalyst precursor, Selectfluor as the oxidant, and LiBF4 as the lithium salt for hypervalent iodine activation, we were gratified to observe the formation of the desired oxazoline 3 in 59% yield as the major regioisomer in nitromethane (MeNO2) solvent (Table 1, entry 1). To further improve

• entry 7 in Table 1, resulting in the formation of the desired oxazoline product 3 in 61% isolated yield. Control reactions in the absence of either the precatalyst or oxidant afforded no product formation (Table 1, entries 11 and 12). The control reaction in the absence of the lithium salt only afforded

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

• breakdown of ethyl vinyl ether and trapping of ethanol, yielding radical 84. To regenerate the photocatalyst, PhSSPh functioned as an oxidant. After protonation upon the β-elimination step, PhS− contributed a hydrogen atom to both 83 and 84, alongside regeneration of the HAT catalyst. Lastly, the acetal

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

• yields, especially 1,2-dibromoethane was the best oxidant. The reaction proceeded in good yield, even if 0.5 equiv of 1,2-dibromoethane were used in this reaction, as shown in Table 1, entries 7 and 8. However, it has been confirmed that this reaction did not proceed when no alkyl halide was added to the

• yield. It is interesting that the reaction proceeded without adding the oxidant (1,2-dibromoethane) when 1,2-dichloroethane was used as the solvent, although a slight decrease in yield was observed (Table 2, entry 14). Based on these results, we selected RhCl(PPh3)3 as the Rh catalyst and THF as the

• Grignard reagents. Rh-catalyzed one-pot Ullmann-type reaction with bromobenzene under optimized reaction conditions. Synthesis of compound 10n as a candidate for an integrin inhibitor. Examination of various alkyl halides as an oxidant. Examination of various Rh catalysts and solvents. Supporting

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• ). We then explored catalytic conditions for the generation of the iodine(III) reagent. Remarkably, when catalytic PhI (0.2 equiv) was employed for in situ generation of Koser’s reagent by using m-CPBA (1.2 equiv) as an oxidant, almost similar results were obtained (Table 2, entry 1) with those obtained

• type haloalkenes. (b) Fate of unsymmetrical dialkyl ketones on direct bromination. (c) This work. Substrate scope. Unless otherwise stated 0.2 mmol of 1 was used and the isolated yields are given. Proposed catalytic cycle. Conditions screening (without oxidant)a. Conditions screening (with oxidant)a

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• selenious acid containing polyaniline via chemical oxidation of aniline with SeO2 as oxidant [45]. Further, Tanini et al. described that selenium dioxide has potential to oxidize aniline to form nitrobenzene in aqueous medium [46]. These findings irrevocably confirmed that aniline undergoes significant

• interactions are rarely reported and currently gaining interest [59]. Computational studies To comprehend the role of electron-donating and -withdrawing groups in arylamine oxidation using SeO2 as oxidant, DFT calculations were carried out on the arylamines and SeO2 using Gaussian 16 [60]. The molecular

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• positions (Equation 3). In the context of the radical process, it is noteworthy that a standard household LED lamp can serve as an efficient initiator, capable of triggering bromine photolysis (Equation 3, top) [45]. Hence, no oxidant-derived residues apart from water are formed and, at the end of the

• reaction time (4 h overall, entries 3 and 4 in Table 1). In these last experiments a whitish solid appeared during addition of the oxidant, initially observed in the one with lower water amount (Table 1, entry 3). The 1H NMR confirmation of the nature of the solid as 3a, makes clear that phase separation

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

• ., in two different periods, reported two paradigmatic examples for indole syntheses. In 2010, they developed the synthesis of 1-(alkoxyarylmethyl)indole-3-carboxylic esters from 2-alkynylaniline imines by using PdI2/KI as catalyst system and oxygen as oxidant [15]. In particular, the reaction was

• indole derivatives were obtained by catalyzing the reaction with 5 mol % of Pd(tfa)2 (palladium(II) trifluoroacetate) and 1.5 equivalents of p-benzoquinone as oxidant in a 1:5 DMSO/MeOH solvent mixture at a temperature between 0 °C and 15 °C and, for a time between 48 and 120 hours depending on the

• ] as catalyst to achieve an NH-indole–C–H carbonylation [57]. A base was added to improve the efficiency of the process and an oxidant to restore the catalytic active species. The reaction was carried out under a low pressure of CO (1 bar) at 110 °C in xylene for 24 hours (Scheme 26). In 2018, the Zhou

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• were oxidized to the corresponding sulfonylquinazolines 8. Inspired by our previous work [19] a TFAA/H2O2 oxidizing system was tried first but yielded several side-products, such as the hydrolysis product and unwanted oxidation of the quinazoline N3 position. Changing the oxidant to mCPBA (with 96

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• unreacted Li+@C60 serves as an oxidant for the reduced monoadducts potentially generated by SET from reactants to monoadducts. These factors contribute to the suppression of multiadduct formation, resulting in the selective generation of the target monoadducts. Specifically, Li+@C60, influenced by the

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

• atmosphere which is an environmentally benign oxidant. Further screening using dioxane as solvent resulted in an increase in the yield to 55%, whilst DMF gave access to 3a in a lower yield (30%) (entries 2 and 3, Table 4). Next, we considered testing the performance of copper iodide (CuI, 20 mol %) as

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

• and colleagues introduced an interesting metal- and oxidant-free photocatalytic C–H alkylation method for coumarins 18 [17]. The method utilized triphenylphosphine and sodium iodide, along with readily available alkyl N-hydroxyphthalimide esters (NHPIs) 3 as the alkylation reagents (Scheme 10

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

• oxidant to generate an oxygen-radical cationic intermediate, which undergoes abstraction of a hydrogen radical (or loses a proton first, followed by an electron) to afford an oxonium ion intermediate. Finally, the oxonium ion is attacked by various nucleophiles to obtain the target functionalized product

• benzylic ethers occurs at room temperature in the presence of Cu(OTf)2/InCl3 as catalysts and DDQ as oxidant (Scheme 3) [51]. By this route, a series of 2-alkoxymalonate diester derivatives was synthesized through direct CDC reaction. The mechanism study showed that the first step of the catalytic cycle

• oxidative alkylation of cyclic benzyl ethers with malonates or ketones. Oxygen is used as a terminal oxidant at atmospheric pressure. The key intermediate of this oxidative coupling reaction is benzyl alcohol intermediate C (Scheme 4) [52]. The generation of N–O radicals from NHPI in the presence of oxygen

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• molecular iron catalyst II and stoichiometric hydroxyiodinane as a terminal oxidant [38]. It is proposed that an azidoiodinane is generated in situ and serves as the radical initiator, generating an azido radical which adds to the less substituted position on the alkene. The resultant transient radical is

• in linear internal alkenes. Building on this key iron catalysis result, our group and that of Shi contemporaneously reported the photochemical diazidation of alkenes using stoichiometric iron and no external oxidant or ancillary ligand, providing a simple protocol for the preparation of vicinal

• azides for a wide range of both activated (benzylic) and unactivated carboxylic acids. Control reactions support the intermediacy of alkyl radicals and the absence of carbocation rearrangements in a variety of probe substrates disfavor the reaction proceeding via RPC. Intriguingly, no additional oxidant

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

The effect of dark states on the intersystem crossing and thermally activated delayed fluorescence of naphthalimide-phenothiazine dyads

• Liyuan Cao,
• Xi Liu,
• Xue Zhang,
• Jianzhang Zhao,
• Fabiao Yu and
• Yan Wan

Beilstein J. Org. Chem. 2023, 19, 1028–1046, doi:10.3762/bjoc.19.79

• chromophores, which are coupled through a Buchwald–Hartwig coupling reaction (another NI-PTZ paper) [39]. The oxidation of the PTZ unit was readily performed by treatment with H2O2 as oxidant (Scheme 1). All compounds were obtained with satisfactory yields and the molecular structures were fully characterized

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• ], antiviral [11][12], antibacterial [13][14][15], antimalarial [16][17], anti-inflammatory [18][19], anti-oxidant [20][21][22], antifungal [23][24] and antibiotic [25][26] and as enzyme inhibitors [27][28]. Several pharmaceuticals, polymers and naturally occurring compounds, including heme, chlorophyll

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

• intact under the reaction conditions without any further oxidation. Different oxidants resulted in different products such as the monoarylated product 118 formed in the presence of TBHP as oxidant and the benzylated product 119 was obtained when potassium persulfate was used. Interestingly, aza-fluorene

• yields (Scheme 28). In this reaction, Grignard reagent 148 was used as arylation source in excess amount as the reagent underwent homocoupling leading to the formation of biaryl systems under the reaction conditions. 1,2-Dichloro-2-methylpropane (149) was found to be an effective oxidant under the

• the use of pyridines for the formation of quinolines and isoquinolines, an oxidant-dependent rhodium-catalyzed C–H annulation of pyridines with alkynes was reported by Li and co-workers [105] in 2011 for the direct synthesis of quinolines 180 and isoquinolines 181 involving a two-fold C–H activation

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• with ortho-substituted anilines is also reported. The key features of the protocol include the use of a green oxidant, a short reaction time (30 min), chromatography-free isolation, scalability, and economical, delivering N-arylsulfonylimines in excellent yields of up to 96%. While the oxidation of N

• used as an additive along with the oxidant K2S2O8 in MeCN, the desired product N-benzenesulfonylimine 2a was obtained in 90% yield (Table 1, entry 3). Subsequently, we carried out further optimization studies by changing the additive, solvent, temperature, and reaction time to obtain the best possible

• -substituted anilines. The key features including the use of a green oxidant, a short reaction time, chromatography-free isolation, and scalability mark a distinction from the contemporary methods. Although we propose a dual role for SO4·− involving both hydrogen atom abstraction (HAT) and single electron

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• , which diminishes the atom economy [2]. To overcome this limitation, the use of molecular oxygen (O2) present in air as an oxidant is one of the ideal solutions [10][11]. The reduction of O2 generates only water as a byproduct, leading to high atom-economy processes. However, the use of O2 as an oxidant

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• the presence of an electrophilic source or an oxidation/ligand exchange in the presence of a nucleophilic source (i.e., AgSCF3) and an oxidant (B in Scheme 4). Finally, after a reductive elimination step, the expected functionalized product 6 is obtained and the palladium catalyst is regenerated. In

• year, the group of Huang reported an elegant and straightforward palladium(II)-catalyzed ortho-selective trifluoromethylthiolation of arenes bearing various directing groups using the nucleophilic trifluoromethylthiolating source AgSCF3 in combination with Selectfluor® as oxidant (Scheme 6, 29 examples

• . Note that, in this process, Selectfluor® is playing a key role. Indeed, using this electrophilic fluorinating source as oxidant generates a Pd(IV)(ppy)F(OAc)2 (ppy = 2-phenylpyridine) complex as intermediate. As the competitive C–F bond formation was disfavored (slow reductive elimination step), the