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

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

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• highly versatile, and a wide range of applications is meanwhile established in organic synthesis [1][2][3][4][5]. They can be applied as mild oxidants [6][7][8], in phenol dearomatizations [9] or in α-oxygenation reactions [10]. In a complemental reactivity, diaryliodonium salts are potent electrophilic

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• achievements, established methods often require the use of stoichiometric oxidants or harsh conditions, thus limiting their broad applicability. Consequently, it is still highly desirable to exploit innovative and convenient methods for the rapid construction of isocoumarins. Enaminones are bench stable and

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• otherwise tedious to synthesize CDIS robustly in short reaction times. A significant drawback still is the use of stoichiometric amounts of chemical oxidants, which decreases the atom economy and necessitates additional workup procedures. A possible solution is the anodic oxidation of iodoarenes as

• electrochemistry is a highly economical tool that avoids chemical oxidants for synthesizing hypervalent iodine reagents [30]. Iodoarenes are suitable and well-established mediators in either in- or ex-cell electrochemical processes [31][32][33][34][35][36]. Nonetheless, HVIs, DIS and CDIS have been generated by

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

• determinant factor for either 8,8’-cis- or 8,8’-trans-cyclization to furan heterocycle cation 218, which serves as the hypothetical common scaffold of the plan. Diverting this mechanistic route to different lignans is possible by introducing nucleophilic additives (e.g., MeOH), oxidants (e.g., Cu(OTFA)2), or

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

• stoichiometric oxidants. The development of organic chemistry is strongly affected by rising “green” demands to synthetic methodologies, including reduction of waste formation, low trace-metal content in drug compounds, high energy-efficiency and selectivity of processes. In the last decade researchers proposed

• active oxidative agent. Asymmetric quaternary ammonium phase-transfer catalysts proved to be effective in the asymmetric nucleophilic epoxidation of electron-poor alkenes by hydroperoxides [70] and the asymmetric hydroxylation of enolizable carbonyl compounds employing O2 or H2O2 as terminal oxidants [71

• amounts of strong oxidants ((NH4)2Ce(NO3)6 [91], PhI(OAc)2 [92], t-BuOOt-Bu [93], etc.) are needed to generate a sufficient concentration of PINO radicals for the effective trapping of C-centered radicals and excess amounts of a CH-reagent are necessary for high selectivity. The electrochemical oxidative

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• ketones and thiourea via an oxidative cyclization initiated by a radical process and a following condensation reaction (Scheme 1c) [29]. Although these methods are practical, most of these strategies require stoichiometric or excess amounts of halogenating reagents or oxidants, which are toxic, hazardous

• . Organic electrosynthesis has been recognized as a green, modern, and safe technique, since electrons can be used as an alternative for oxidants or reductants [30][31][32][33][34][35][36][37][38]. During our continuous interests in halide-mediated indirect electrolysis [39][40][41][42], we have achieved

• performed in an undivided cell with NH4I as the mediator and cheap graphite plate as the working electrode. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diones proved to be compatible with the protocol. Since external oxidants and

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• reaction of hydrazones and p-benzoquinones [16], and Co3+/Cu2+-catalyzed C−N/N−N coupling of imidates with anthranils as both aminating reagents and organic oxidants [17]. Additional established routes to 1H-indazoles comprise transition metal‐catalyzed [18][19][20] and metal-free [21][22] intramolecular

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• alcohol derivatives. The present transformations smoothly proceed in a simple undivided cell under constant current conditions without the use of external chemical oxidants/reductants, and transition-metal catalysts. Keywords: alcohols; dimerization; electrooxidation; electroreduction; paired

• direct oxidation of sec-alcohol 1 to ketone 3 could also proceed under the present reaction conditions. Conclusion In conclusion, we have developed the sacrificial anode-free electrochemical protocol for the synthesis of vic-1,2-diols from sec-alcohols without external chemical oxidants or reductants

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• -acyliminium ions in chemical methods has been generally accomplished by the reaction of amides with chemical oxidants, such as peroxides and persulfates at high temperature (path a in Scheme 1) [10][11][12][13]. A metal catalyst or a photocatalyst consisting of metals, such as ruthenium or iridium, is also

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• ][18][19][20][21][22] not only because it employs the passage of charge instead of chemical oxidants or reductants but also offers opportunities for the precise control of reactivity by "dialing-in" the specific potential on demand [23][24][25]. Specifically, the electrochemical oxyfunctionalization of

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• sophisticated platforms such as metal nanoparticles, all of which have been reviewed thoroughly in the literature [4][5][6][7][8]. However, the methods referenced so far display one or more of the following setbacks: involvement of harsh oxidants or reductants, use of expensive metal catalysts, need for

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• odor”. Alternatively, the reaction mixture is pumped to an oxidation module in which the pinacol boronates are mixed with a solution of sodium perborate in water/tetrahydrofuran to perform oxidation to the corresponding alcohols 20 at 40 °C in 60 s. In order to quench remaining oxidants, the reaction

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• continuous process could be established by oxidation with molecular oxygen introduced into the reaction stream via a tube-in-tube membrane reactor, a process which should be very attractive for industrial applications, as oxygen or air act as cheap and environmentally friendly oxidants [82]. An interesting

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• spectroscopy (Figures S40–S76 in Supporting Information File 1). All experiments were performed without additional oxidants and solid or liquid additives. The presence of the PdII-catalyst in the reactions of L2–5 with NXS resulted predominantly in LnX-I products or a mixture of products that were mono- or

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• system using oxidants other than air [28][29][30] encouraged us to develop a highly productive flow system with air. Herein, we report that rapid gas–liquid oxidation of cyclohexene with air in the presence of isobutyraldehyde as a sacrificial agent to synthesize cyclohexene oxide is successfully

• oxidation and decomposition of oxidants generated from air and aldehyde. Furthermore, the fast epoxidation is applicable for the continuous production process of cyclohexene oxide for 1 hour maintaining stable operation. Results and Discussion Batch experiment of epoxidation of cyclohexene with air As an

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

• the other hand, increasing the amount of DDQ to 1.2 equiv resulted in 98% yield of the product (Supporting Information File 1, Table S1, entries 1 and 3). Further studies revealed that other commonly used oxidants such as PIDA and oxone gave 30% and 61% the desired product, respectively (Supporting

• Information File 1, Table S1, entries 4 and 5). When molecular iodine or NIS were used as oxidants, product 5a was obtained in 83% and 80% yield, respectively (Supporting Information File 1, Table S1, entries 6 and 7). However, the yield of the desired product 5a slightly decreased to 92% with lowering of the

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• menadione. Oxidation of 2-methylnaphthalene Menadione synthesis through the oxidation of 2-methylnaphthalene (16) includes the use of oxygen-rich oxidants using various reaction conditions and a broad range of well-succeeding methodologies has been reported. A summary is presented in Table 1 and will be

• one of the most studied and used oxidants has been H2O2. Yamaguchi and co-workers described the oxidation of 16 with aqueous H2O2 in the presence of a palladium(II)-polystyrene sulfonic acid resin (Table 1, entry 4) [50]. According to the authors, in the absence of the catalysts, the oxidation took

• heteropoly acids [71], molecular oxygen [72][73], and organic peroxides [74]. Matveev and co-workers studied phosphomolybdovanadium heteropoly acids of Keggin-type with the general structure H3+nPMo12-nVnO40 (HPA-n) and their acidic salts as reversibly acting oxidants to convert 17 to 10 (Table 2, entry 8

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• iodine-mediated cyclisation with other oxidative conditions. A range of oxidants was investigated (Table 1), with only N-chlorosuccinimide (NCS) [34] and iodine resulting in the formation of product (entries 1 and 2, Table 1). As iodine yielded superior results, we opted to transfer this reaction from

• of complex oxadiazoles. Continuous flow scale-up reaction with in-line quench and extraction. Continuous flow setup equipped with in-line extraction and purification. Screening of oxidants for cyclisation of acyl hydrazone. Optimisation of iodine-mediated cyclisation in continuous flow mode

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• etc. Our studies disclosed that many of the reports were mainly focusing on the oxidative cyanation of tertiary amines. Extensive research was carried out in the cyanation of tertiary amines using different oxidants such as O2, H2O2, and TBHP. Ruthenium was also found to be effective in the cyanation

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

• ) [94]. Interestingly, the protocol used air as the oxidant, avoiding the use of stoichiometric oxidants like previous radical cyclization cascades. Generally, substrates with an electron-withdrawing group afforded the product in greater yield. The reaction proceeds through the formation of a sulfonyl

• 106 (Scheme 21) [104]. The use of Ag2CO3 as a SET oxidant was shown to be key for the success of the reaction, as typical organic oxidants, like peroxides, displayed low activity. No clear trend was observed for the difference in efficiency between the Fe catalysts used. It was noted the use of the Fe

• operate in the absence of any external oxidants under an inert atmosphere. Although not investigated, Loh’s transformation most likely begins with the generation of an aryl radical from the reduction of the diaryliodonium salt with Fe(II) which subsequently abstracts a hydrogen from CH2Cl2 to generate an

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

• group (Scheme 2) [33]. In contrast to transition-metal-mediated approaches [27], metal-free oxidative methods are attractive not only from an ecological point of view, but also due to the typically low cost of the applied oxidants. Biarylcarboxaldehydes were cyclized to fluorenones using K2S2O8 [34

• of oxidizing agents, oxidizing systems, and radical initiators on a set of model molecules 2 (see Table 1) in a preliminary screening for suitable oxidants for the intramolecular ring-closure reaction. The set of model molecules 2 bears different benzylic N-containing functional groups, including

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

• the oxidation of the tetrahydroisoquinoline to an iminium intermediate with various chemical oxidants such as peroxides and DDQ followed by reaction with the copper acetylide species to deliver the 2-substituted tetrahydroisoquinoline product (Scheme 1A). These methods usually require elevated

• temperatures [3][4][5], prompting the development of mild conditions by merging photoredox catalysis with copper catalysis (Scheme 1B) [8][9]. Notwithstanding of these outstanding achievements, noble metal-based catalysts and chemical oxidants are employed under these photochemical conditions. Organic

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• the copper-catalyzed oxidative coupling of alkynes, nucleophiles (e.g., phenols 25 and 28; amines 24, 27, 29, and 32; 2-hydrazinylpyridine 26; alkyne 33; and alcohol 30), and oxidants (benzoquinone or O2). Based on the literature and mechanistic experiments [72][73], the reaction is initiated by the

• photoirradiation of in situ-generated CuI phenylacetylide. From the excited state of CuI phenylacetylide an electron is transferred to the oxidants (benzoquinone or O2) via a SET, thereby forming a CuII phenylacetylide species and a radical anion. The resulting CuII phenylacetylide species is involved in the bond