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

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• performed radical trapping experiments using TEMPO and BHT in the reaction of substrate 1c (Figure 5a). Under the standard reaction conditions in the presence of TEMPO or BHT, the expected product 2c was formed in 66 and 72% yields. These results indicate that a radical pathway may not be involved in the

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• allow for indirected C–H transformations and herein, homolytic C–H cleavages are described for transformative manganese-catalyzed brominations of tertiary C–H bonds [14]. Finally, electrooxidation enabled the site-selective alkynylation of tetrahydroisoquinolines within a TEMPO/copper regime [15]. As

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• could also be arylated using the same protocol (18, 34%). Mechanistic investigations were conducted to support the proposed HAT mechanism by DABCO. Radical trapping with TEMPO completely shuts down product formation, proving a radical mechanism is operating. Moreover, an acyl-TEMPO adduct was formed and

• amines (Table 1, entries 9 and 10 and Supporting Information File 1, Scheme S2). Radical trapping experiments with TEMPO also showed a radical path mechanism, and the acyl radical was detected as an intermediate (Supporting Information File 1, Table S4). The absence of product formation in the Giese

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• -rich phenols, as well as those bearing halogen substituents, were suitable substrates under these reaction conditions. In Lei’s report, the reaction shuts down in the presence of TEMPO and in the absence of DDQ; thus, the formation of a phenoxy radical was proposed. In 2018, Zhong and co-workers

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• of the radical inhibitor 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) was subjected to the model reaction system, however, the reaction was not inhibited (Scheme 6B). This result suggests that no radical pathway is involved in this transformation. Based on the above experiments, a proposed mechanism

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• nitrate (CAN) [41], 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO)/CuCl [51], K2S2O8 [36], dimethyl sulfoxide (DMSO)/O2 [52], PhI(OAc)2/benzoyl peroxide (BPO) [47], Dess-Martin periodinane, N-bromosuccinimide (NBS), N-hydroxyphthalimide (NHPI)/Co(OAc)2/O2 [53], H2O2/tetrabutylammonium iodide (TBAI) [43], CBr4

• cyclization was explored. As a radical mechanism appeared very likely, the standard reaction with aqueous TBHP was run in the presence of the radical quenchers TEMPO and BHT (4 equivalents respectively) in separate experiments. While trapping a radical species of interest in form of a TEMPO ester was

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• terminal alkynes has been achieved in a continuous-flow microreactor through 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/copper relay catalysis. The reaction is easily scalable and requires low concentration of supporting electrolyte and no external chemical oxidants or ligands, providing straightforward

• electrochemistry is an ideal tool for promoting dehydrogenative cross-coupling reactions as no external chemical oxidants are needed [11][12][13][14][15][16][17][18][19]. In this context, Mei and co-workers have reported an elegant TEMPO/[L*Cu] co-catalyzed asymmetric electrochemical dehydrogenative cross-coupling

• electrocatalytic dehydrogenative cross-coupling reaction of tetrahydroisoquinolines with terminal alkynes in continuous flow (Scheme 1D). These reactions require low loadings of supporting electrolyte and proceed through Cu/TEMPO relay catalysis without need for additional ligands. Results and Discussion The

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• amines were reacted well, while amines substituted with strongly electron-withdrawing (such as nitro and trifluoromethyl) groups, heteroaryl amines, and aliphatic amines were not compatible. Control experiments showed that the addition of 2.0 equiv of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) under

• standard conditions could inhibit the formation of target product. In contrast, the compound TEMPO–N3 was detected by GC–MS analysis. Based on the radical trapping experiment and previous reports, the reaction may undergo a radical process. 2-Carbonylpyrrole is a key subunit of many bioactive natural

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• subsequent oxidation of the primary alcohol with the TEMPO/BAIB system facilitated the formation of pyrone 107. Initially, Sabitha and Raju intended to synthesize brevipolides K and L by esterification of this furanyl alcohol 107 with (Z)-4-OMe- and (Z)-4-OPMB-cinnamic acid 118 and 119, respectively

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• inhibition of the catalytic cycle upon the addition of TEMPO revealed that the reaction proceeds through radical intermediates. Next, we carried out UV–vis monitoring experiments in order to verify whether the interaction with the substituted benzyl alcohols and CeIV could lead to a ligand-to-metal charge

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -membered sulfur-containing cycle (Scheme 23) [52]. Some reactions were performed to screen the reaction mechanism in detail. To find out if the reaction proceeds through a radical pathway, tetramethylpiperidine-1-oxyl (TEMPO) was added to the reaction. The corresponding product was obtained in high yield

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ′-carboxylic acids 65a–c which in turn were prepared through the (2,2,6,6-tetramethylpiperidin-1-oxyl) (TEMPO) and 1,1-bis(acetoxy)iodobenzene (BAIB)-assisted oxidation of the 5′-hydroxymethylene group in adenosine/uridine by following the methodology developed by Epp and Widlanski [53]. The nucleoside-5

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• posthumously in 1919 [35]. In 1894, Guareschi reported the first high-yield synthesis and the structure elucidation of triacetonamine (6, Scheme 3) [35][36][37], the sterically hindered amine that is the starting material for the synthesis of the popular oxidant TEMPO [38]. Triacetonamine had first been

• observation was that the presence of radical traps, such as 4-hydroxy-substituted TEMPO, was detrimental for the reaction, which evidently involved free radicals. Anaerobic conditions (degassing with argon) inhibited the reaction, which could be restarted when oxygen was bubbled into the solution. This