Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• -positions to the ester group were all well-tolerated (Table 3). To gain further insights into the reaction mechanism, we conducted control experiments. Given the utility of diaryliodonium salts in radical chemistry, we introduced 2 equivalents of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2 equivalents

• this approach. Arylation reactions of aromatic compounds and reaction patterns of ortho-functionalized diaryliodonium salts. Mechanism study. Standard conditions: 1 (0.3 mmol, 1 equiv), 2 (0.33 mmol, 1.1 equiv), Cu(OAc)2 (10 mol %), DCE (2 mL), 80 °C, 3 hours. TEMPO = 2,2,6,6-tetramethylpiperidine-1

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• measured by the ESR spin trapping method under irradiation of visible light (527 nm green LED). 4-Oxo-TEMP was used as a spin trapping reagent to form an adduct with 1O2, i.e., 4-oxo-TEMPO, which was observed by ESR (Figure 7b). As shown in Figure 7a, upon visible light irradiation, three peaks

• corresponding to 4-oxo-TEMPO were observed in the solution of C60–oligo-Lys (5a), similar to the results with rose bengal, a standard compound for 1O2 generation. By taking into account that the absorption intensity of 5a at 527 nm used for the photoirradiation was ≈10 times smaller than that of rose bengal, it

• s, number of scans: 1. b) Scheme for the photoinduced 1O2 generation by C60 and reaction with spin trapping reagent 4-oxo-TEMP to form 4-oxo-TEMPO. Supporting Information Supporting Information File 4: Details for the synthesis of 5a–c and intermediates as well as spectral data. Acknowledgements

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• (TEMPO) and the corresponding radical-trapping product A could be confirmed by HRMS of both reaction mixtures, unambiguously supporting radical mechanisms (Scheme 4a). The reaction with styrene was conducted under standard conditions, but no product X could be detected, indicating the cationic

• ) Radical trapping experiments with TEMPO. b) Exclusion of possible intermediate. c) Subjecting the product Z-6i to the standard conditions. d) The control reaction with HPd(PPh3)2Cl. e) UV–visible absorption analysis. Proposed mechanisms for the carboamination of 1,3-dienes or allenes with diazo esters and

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• indicated that both the acylamino and quinoline N motifs played a significant role. On the other hand, the stoichiometric amount of free radical inhibitors, including TEMPO and BHT, could not comprehensively suppress the reaction. Based on these experimental results and previous works [30][31][32], a

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• . The addition of a typical radical scavenger – TEMPO (2,2,6,6-tetramethylpiperidin-1-yloxyl) significantly inhibited the reaction (as shown in Scheme 3), suggesting the involvement of radical species during the reaction process. Moreover, the radical trapping product was detected and confirmed via 19F

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• -tetramethylpiperidine 1-oxyl (TEMPO), 2-mercaptoethanol and 2-mercaptoethylamine hydrochloride, respectively, showed that C-centered radicals contribute even more to the DNA damage than hydroxyl radicals (Supporting Information File 1, Figure S17B). It should be noted, however, that these scavengers may also intercept

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

• successful nitroxide-mediated polymerization (NMP). In 1993, Georges et al. used benzoyl peroxide (BPO) as the initiator and 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) as the control agent. It was called a bicomponent initiating system containing both stable free nitroxide and a conventional thermal

• can decompose to produce a stoichiometric pair of the primary initiating radical and a nitroxide radical, thus combining the roles of a conventional initiator and a control agent. The mechanism is shown in Scheme 4 [35]. Due to the steric effect of TEMPO, the dissociation rate constant, kd, of the

• corresponding alkoxyamine is very low and it tends to undergo β-elimination in acrylic systems. Thus, TEMPO is only suitable for the polymerization of styrenic monomers at a high temperature and for long time [36]. Functionalized TEMPO was therefore developed for the polymerization of other monomers, such as

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• . It was found that the desired product could be obtained in 87% yield (Scheme 4). Next, some control experiments were carried out to study the reaction mechanism. We found that the reaction of compound 3a could not be inhibited by TEMPO and BHT under the standard conditions. Therefore, it is assumed

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• ·H2O, FeSO4, and Fe(acac)3 resulted in inferior chemical yields. Employment of 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO) as a radical trapper inhibited the reaction, which proved that a radical process was involved. The reaction was initiated by a single electron transfer (SET) process from the

• in the presence of TEMPO, followed by insertion of an isocyanide molecule 166 or other nucleophiles 161 (Scheme 72) [102]. By studying the spectroscopic evidence, the authors found that both sulfenyl halide 165 and N-sulfenylsuccinimide 1 intermediates were involved in the reaction. Removal of TEMPO

• as a radical initiator from the reaction mixture did not result in product formation so, it seems that the reaction moved through a radical route for the formation of sulfenyl halide I, and N-sulfenylsuccinimide II. The use of azobisisobutyronitrile (AIBN) instead of TEMPO also resulted in 85% yield

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• recyclable amine species for comparison [32]. The ferrocene, TEMPO, and viologen derivatives shown in Figure 4 are used in aqueous organic redox flow batteries [59][63]. The batteries store charge in concentrated aqueous solutions of small organic redox mediators that can be oxidized and re-reduced (or

• . TEMPO and ferrocene derivatives are used to store positive charge in RFB catholytes [59][63]. Both parent compounds undergo reversible one-electron oxidation and re-reduction but had to be modified to improve their solubility. TEMPTMA and both ferrocene derivatives have one or more ammonium groups added

• to the core TEMPO or ferrocene charge-carrying moiety. This both increases the solubility of the species and the oxidation potential in aqueous media. TEMPOL uses an alcohol group to the same effect. Redox couples for RFB catholytes are optimized for increasing the oxidation which decreases their

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• that reacted 31 with secondary amines 34, which produced densely functionalized N-heterocycles 35 that incorporated two of the ylide’s β-dicarbonyl motifs (Scheme 6) [123]. Though these reactions were conducted at 70 °C, free carbenes were not involved. Both TEMPO and 1,4-dinitrobenzene inhibited the

• ]. The authors discounted a free carbene-based C–H insertion because conducting the reaction in the presence of the radical trap phenyl N-tert-butyl nitrone (PBN) and the radical scavenger TEMPO resulted in decreased yields and isolation of their iodonium ylide adducts. Additional kinetic isotope effect

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

• donor were all essential for product formation. A diminished yield of 19% under aerobic conditions indicates the involvement of a triplet excited state. Addition of i) 2,2,6,6-tetramethylpiperidine-N-oxide (TEMPO) as a free-radical quencher or ii) 1,4-dinitrobenzene as an electron trap inhibited product

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• successfully obtained in 45% yield, which indirectly proved the existence of an oxime sulfonyl ester intermediate (fluorosulfonate). As shown in Scheme 5b, in the presence of one equivalent of TEMPO, a commonly used radical scavenger, the yield of 3aa significantly decreased, in addition, the reaction was

• completely inhibited when the amount of added TEMPO was increased to 2 equivalents. Based upon the preliminary results and previous reports of this class of transformation [26][30][36][37][42][60][61], a plausible mechanism for the base-promoted, SO2F2-mediated ring-opening cross-coupling of cyclobutanone

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

• CrO2 [9], PhI(OAc)2/I2 [10], TEMPO [11], NHPI [12], and metal catalysts [13], suffer from serious limitations including the use of metal catalysts, high temperature, risk of explosive hazards, production of large waste, and often low yield (Scheme 1c). Thus, an environmentally benign method that could

• purification. Next, in order to determine whether the reaction proceeds via a radical pathway, we performed a control experiment. When substrate 1a was treated with the radical scavenger TEMPO under the optimized reaction conditions, the formation of product 2a was completely suppressed (Scheme 4). This

• of 1 equiv of K2S2O8 and the corresponding ortho-substituted anilines 3 (1.2 equiv) and stirring at 80 °C for 2 h. Yields correspond to isolated products. Control experiment with TEMPO. Plausible mechanism for the K2S2O8-induced oxidation of N-(arylsulfonyl)benzylamines. Plausible mechanism for one

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

• -oxyl (TEMPO) oxidation [8]. TEMPO oxidation, in particular, has been successfully applied on a manufacturing scale as a low-cost and green oxidation method [9]. However, these oxidation processes generally require stoichiometric oxidants, and reduced byproducts must be purged in a purification step

• (Table 1, entry 2) [39]. While this led to a simpler catalyst system, nor-AZADO is expensive. Hong and co-workers have developed a low-cost catalyst system using TEMPO and nitrate salts [40]. Fe(NO3)3 (Table 1, entry 3), Cu(NO3)2 (Table 1, entry 4), Zn(NO3)2 (Table 1, entry 5) worked as catalysts

• combined with TEMPO. The reactivities were significantly lower than those in Table 1, entries 1 and 2, but the reaction could be completed overnight at room temperature. The catalysts were completely dissolved in AcOH and the reaction mixture remained in the solution throughout the reaction in entries 3–5

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• reaction conditions, generating the corresponding acetoxymalonylated products 4u–w in good to excellent yields. Several control experiments were performed to gain insights into the mechanistic pathway of this reaction. Firstly, a radical scavenging experiment using the radical scavenger TEMPO was performed

• (Scheme 3A). Upon analyzing the reaction mixture of 1a and 2a under standard conditions in the presence of TEMPO, we found only a trace of the desired product 4a. At the same time, a TEMPO-DEM adduct 7 and TEMPO-OAc adduct 8 were identified by the HRMS analysis of the crude reaction mixture, indicating

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• that DBU was essential for the reactivity, since no reaction occurred in its absence (entry 3, Table 1). Reactivity was also inhibited under an aerobic atmosphere and in the presence of 2,2,6,6‐tetramethylpiperidinyloxyl (TEMPO). These experiments are consonant with the occurrence of a radical

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• % overall yield after 8 steps. Selective demethylation led to hydroxyisocorniculatolide B, 175 in 11% overall yield after 9 reaction steps (Scheme 33) [71]. The intermediate 173 was also submitted to an oxidation using BAIB and TEMPO [72], followed by reduction of the ester using LiBH4 to provide the seco

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• formation of the fused cyclobutane acid 162 as the desired precursor for the cyclooctane formation. The ring expansion was achieved in the presence of an iridium catalyst and under blue LED irradiation, via the trapping by TEMPO or O2 of the cyclobutyl radical resulting from decarboxylation, which allowed a

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• ) in 86% yield. To find out more information about the mechanistic route of the reaction, we performed a control experiment in the presence of TEMPO as a radical scavenger as depicted in Scheme 6. The reaction of pyrazole-3-carbaldehyde 1, pyrrolidine (A) and elemental sulfur in the presence of 1.1

• equiv of TEMPO delivered the targeted product in 76% yield. On the basis of this experiment, it was concluded that TEMPO did not affect the progress of the reaction and the formation of product 1A. Hence, a radical mechanism of the reaction may be ruled out. The successful synthesis of pyrazole C-3/4/5

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• oxindole 3ap in 63% yield. In order to gain insight into the reaction mechanism, some control experiments were further performed. When a radical scavenger such as 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) was added to the catalytic system under standard conditions, the reaction was fully inhibited, and

• a TEMPO-trapped adduct (4) was detected by HRMS (Scheme 4a). Moreover, the radical-mediated ring-opening product 3am could be obtained with 66% yield in a radical clock experiment when redox-active ester 5 was engaged to react with acrylamide 1a under standard conditions (Scheme 4b). Finally, it

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• oxidative decomposition to the core of 194 and 195. FGI followed to complete targets 196–200 (Scheme 16). Pyrroloindoline natural products (Knowles 2018) [102]: In 2018, Knowles’ group demonstrated the ability of TEMPO to act as a trap for radical cations arising from the single-electron oxidation of

• ). Thus, upon irradiation, iridium polypyridyl photocatalyst allowed the oxidation of the phosphate complex 207 to radical cation 206, which can be readily trapped by TEMPO, and hence stabilizing the imine and allowing cyclization with the pendant amine to form the pyrroloindoline core 210 in 81% yield

• of (−)-FR901483 (160) and (+)-TAN1251C (162, Gaunt). Divergent synthesis of bipolamines (Maimone). Flow chemistry divergency between aporphine and morphinandione alkaloids (Felpin). Divergent synthesis of pyrroloazocine natural products (Echavarren). Using TEMPO to stabilize radicals for the

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• proceeds with the preservation of stereocenters. It is tolerant to a wide range of functional groups, which makes it compatible with natural substances and complex biologically active compounds. TEMPO and its derivatives are successfully used as electrocatalysts. 4-Acetamido-2,2,6,6-tetramethylpiperidin-1

• electrocatalytic efficiency (TON up to 2000) was achieved using the TEMPO derivative non-covalently immobilized on the surface of a carbon cloth anode due to the π–π stacking interaction between the pyrene fragment of the catalyst and the electrode surface [103] (Scheme 15). However, this method is not compatible

• electrolysis (2–3 F/mol) until potential rised by 0.5–0.8 V above initial potential; undivided cell, reticulated vitreous carbon (RVC) anode(+):Pt cathode(−). Chemoselective alcohol oxidation catalyzed by TEMPO. ABNO-catalyzed oxidative C–N coupling of primary alcohols with primary amines. ACT-catalyzed

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• -diisopropylethylamine; OLED, organic-light emitting diode; SCE, saturated calomel electrode; TADF, thermally activated delayed fluorescence; TEMPO, 2,2,6,6-tetramethylpiperidinyloxyl; TIQ, triazoloimidazoquinoxaline. UV–vis absorption spectra of the obtained metal complexes (18 µM solutions) in acetonitrile at 20 °C