Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• endoperoxygenase NvfI. Keywords: biosynthesis; endoperoxide; enzyme; natural products; X-ray crystallography; Introduction Endoperoxide-containing compounds form a large group of natural products with cyclic peroxide structures [1][2][3][4][5]. These compounds are widely distributed in nature, and many

• endoperoxide containing alkaloids, terpenoids, and polyketides have been isolated from plants, animals, bacteria, fungi, and other organisms (Figure 1) [6][7]. Because of the high reactivity of the cyclic peroxide O–O bond, these compounds exhibit various biological activities [1][2][3][4][5]. For example

• ], which share ≈60% amino acid identity [33]. Both isoforms catalyze the incorporation of two oxygen atoms into arachidonic acid (AA) to form an endoperoxide between C9 and C11 and a peroxide at C15 to generate prostaglandin G2 (PGG2) (Scheme 1) [24][34]. Subsequently, the 15-hydroperoxide in PGG2 is

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

• performed chemical reactions. Interesting examples are MagTrieveTM, which contains CrO2 and nickel peroxide (NiO2). Both were mixed with MagSilicaTM and used as fixed-bed materials (Scheme 11, case C) [75]. At this point, it is important to note that CrO2, despite its paramagnetic properties, does not heat

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

• 1,2-dichloroethane (45 mL) was stirred vigorously with air bubbling at the reaction temperature for 30 min to initiate the peroxide formation. Then, a solution of cyclohexene (3.25 mmol) in 1,2-dichloroethane (5 mL) was added. The inner pressure was released through a thin needle on the top 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

• •−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and hydroperoxyl radical (•OOH) (Figure 3) [35]. Additionally, the menadione semiquinone radical can participate in another redox cycle, such as, the Fenton reaction, also resulting in the production of hydroxyl and hydroperoxyl radicals (Figure 3) [39][40

• menadione (10), as was demonstrated by Minisci and co-workers [66]. In this work, the oxidation of 17 with 60% aqueous hydrogen peroxide, using bromine and sulfuric acid as catalysts, provided menadione in 90% yield (Table 2, entry 1) [66]. According to the proposed mechanism, the first step involves the

• different benzylamines (1:1:2.2) (Table 2, entry 7). The reaction was carried out in tert-amyl alcohol (TAA), which led to product 10 in 55% yield and 99% conversion of 17 [55]. In addition to hydrogen peroxide, other oxidizing agents can be used in the synthesis of menadione (10) from 17 and include

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

• the cyanation reaction. This strategy utilized eco-friendly hydrogen peroxide and molecular oxygen as the oxidant system. This method was found highly favorable to tertiary amines with electron-donating substituents. The first report on an MCM-41-immobilized N-alkylethylenediamine Ru(III) complex (MCM

• to furnish the desired products in good yields. In 2008, they described the scope and mechanism of the oxidative cyanation of tertiary amines using H2O2 and O2 [34]. They pointed out the fact that the hydrogen peroxide system was found to be more efficient in catalyzing the cyanation reaction of

• cyclic amines than the aerobic oxidation system. The catalytic cycle for the hydrogen peroxide system involves the formation of the oxoruthenium species (A) and the low-valent ruthenium species (B), whereas the aerobic oxidation system includes C–H activation and a subsequent reaction with molecular

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• . While anthranilamide (5) bromination with N-bromosuccinimide in acetonitrile at room temperature [29] furnished 2-amino-5-bromobenzamide (6a) in 78% yield, iodination of 5 with iodine in the presence of hydrogen peroxide in water [30] at 50 °C provided 2-amino-5-iodobenzamide (6b) in 89% yield. After

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

• isotope studies revealed the cleavage of the C(sp3)–H bond may be involved in the rate-determining step of this transformation. Mechanistically, prototypical homolysis of the peroxide in the presence of the Fe(II) catalyst will generate the alkyl radical 78 formed via hydrogen abstraction. The

• synthesis of 3‐silylspiro[4,5]trienones 93 in good yield (Scheme 17) [95]. Compared to previously reported inter-/intramolecular CDC cascades, the authors were able to capture the post-cyclization aryl radical with the peroxide initiator rather than simply terminating the reaction with protonation. In terms

• of the scope of the reaction, substrates bearing an electron-rich functionality were less reactive than substrates with electron-deficient groups. Isotopic labeling revealed the oxygen functionality installed came from the peroxide initiator rather than the water present, suggesting the water plays

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• hydrogen peroxide catalyzed by phosphotungstic heteropoly acid. Each of the key reactions proceeded with an excellent diastereoselectivity (dr > 95:5). (±)-Codonopsinol B was prepared in 10 steps with overall 8.4% yield. The antiproliferative effect of (±)-codonopsinol B and its N-nor-methyl analogue was

•  1, page S25). Although the syn selectivity was further improved (80:20) by using the in situ-generated trifluoroperoxyacetic acid [28], the reaction suffered from formation of a high level of impurities. Gratifyingly, this issue has been overcome by the use of hydrogen peroxide in the presence of

• formation. Since the aqueous tungstic acid-catalyzed hydrogen peroxide epoxidations of monosubstituted allylic alcohols usually proceed in anti (erythro) stereoselective fashion [32], we propose that the high syn selectivity can be attributed to the presence of the unprotected hydroxy group in the

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

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

• electrochemical microreactors can be a viable tool for developing efficient transition-metal electrocatalysis. C(sp3)–H alkynylation of tetrahydroisoquinolines. L* = chiral ligand. TEMPO = 2,2,6,6-tetramethylpiperidine 1-oxyl. DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. BPO = benzoyl peroxide. Substrate

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

• photolysis of DTBP producing an alkyl radical, which reacted with nitrogen-containing compounds to give the target products 63. The catalytic cycle involves a photoinduced copperII peroxide system with an in situ-generated CuII–N complex as the key catalytic species. In 2020, Anandhan’s group [98] developed

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• cyclization of alkenyl α-aminophosphonates. Cyclization of 4-cycloocten-1-ol with Hg(OAc)2 forming fused bicyclic products. trans-Amino alcohol formation through Hg(II)-salt-mediated cyclization. Hg(OAc)2-mediated 2-aza- or 2-oxa-bicyclic ring formations. Hg(II)-salt-induced cyclic peroxide formation. Hg(OAc

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• often requires relatively high catalyst loadings, directing groups, high reaction temperatures (100–160 °C), stoichiometric additives, or oxidants such as peroxide or silver salts that can be undesirable for large scale synthesis. Recently, photoredox dual catalysis has witnessed significant

• -amino C(sp3)–H bonds using di-tert-butyl peroxide (DTBP) or dicumyl peroxide (DCP) as the methyl source under mild conditions [93]. Based on the substrate structure and peroxide choice, the authors developed four sets of reaction conditions (Scheme 29) [93]. In these reaction conditions, photocatalyst

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• iron-based small molecule catalyst and hydrogen peroxide as oxidizing agent (Scheme 25A and B) [156]. This pioneering methodology changed the way how complex molecules and pharmaceuticals are synthesized, by using the steric and electronic properties of the substrates to achieve selectivity, without

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

• Br2, MnO2, hypervalent iodine reagents, chromium-based reagents, activated dimethyl sulfoxide, KMnO4, OsO4, or metal-based catalysts and peroxide were used [7][8][9][10][11][12][13][14][15][16][17]. Most of these protocols produce harmful waste and some of the oxidizing reagents are considered toxic

• •−. Photolysis of the CeIV–OBn complex (II), leads to the formation of the corresponding benzyloxy radical (III) and regenerates the CeIII species. A further abstraction of a benzylic hydrogen atom by the peroxide radical then generates the final product 2 [48]. However, at this moment we cannot exclude the

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• of the potential of ATR in olefin hydrofunctionalization is the methodology developed by the Liu group [119], in which a carbon-centered radical is generated from simple alkanes instead of the more usual halogenated compounds. The authors reported that, in the presence of dicumyl peroxide (DCP) as a

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• , ascorbic acid/hydrogen peroxide, respectively. The mixture was immediately placed in a Petri dish to complete the gelation via free radical polymerization under dark conditions. After 3 hours, the resulting hydrogel was purified with water to remove the unreacted species (monomers and redox mediators

• isothiocyanate conjugate (FITC-Albumin, Sigma-Aldrich), calcium chloride (CaCl2, 97%, Alfa Aesar), cyanuric acid (98%, Sigma-Aldrich), fluoresceinisothiocyanat-dextran (FITC–Dextran, 10.000 Mw), hydrochloric acid (HCl, 37%, Sigma-Aldrich), hydrochloric acid (1 M solution, Sigma-Aldrich), hydrogen peroxide (30

• -W). 9 g freshly prepared CM-W, 0.8 g DMA, 0.150 g MBA and 0.150 g AsA were weighted into a flask, mixed for 5 minutes, then sonicated for 20 seconds. Following that, 1.5 mL hydrogen peroxide solution was injected into the mixture and placed in a Petri dish after mixing thoroughly. The Petri dish was

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• such as lead tetraacetate, potassium permanganate, or refluxing hydrogen peroxide were shown to produce urea-derived degradation products [3]. Biguanides also possess a remarkable capability to form stable metal complexes, a property that was already noticed by B. Rathke in 1879 [4]. Indeed, he relied

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• radical C(sp3)−H halogenation at the benzylic and allylic position using N-halosuccinimide with azobisisobutyronitrile or benzoyl peroxide as a radical initiator is known as the Wohl–Ziegler bromination reaction, which requires heating, acidic/basic conditions, and/or UV irradiation (Scheme 1a) [17][18

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• %. Synthesis of 1. Reagents and conditions: (a) 1,3-dibromo-5,5-dimethylhydantoin, benzoyl peroxide, (CH2Cl)2, reflux, 4 h, 88%; (b) 5,5-dimethyl-3-(4H-isoxazolyl) carbamimidothioate·HCl, K2CO3, MeCN/H2O, 50 °C, 1.5 h, 73%; (c) H2O2, Na2WO4, MeCN/H2O, 45 °C, 1.5 d, 66%. Synthesis of 11–13. Reagents and

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• phosphorus atom of 2 was carried out; the results are shown in Scheme 1. The reaction of 2 with hydrogen peroxide or elemental sulfur afforded the corresponding phosphine oxide 3 and sulfide 4 in 92% and 88% yield, respectively. Treatment of 2 with methyl triflate afforded phospholium triflate 5 in 81% yield

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• minutes, 30% hydrogen peroxide solution (0.52 mL, 0.57 g, 5.0 mmol, 2.0 equiv) was added dropwise. The color of the reaction mixture changed from colorless to yellow. The reaction mixture was stirred for 30 minutes at room temperature. After completion of the reaction, EtOAc (10 mL) was added, causing

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• greener oxidizing agents as molecular oxygen, hydrogen peroxide or tert-butyl hydroperoxide (TBHP) [14][15][16][17]. However, using any of these oxidants alone results in considerable low reactivity and selectivity in olefin epoxidation reactions. Thus, several transition-metal-based catalytic methods

• solvent (DMF, MeCN, ethyl acetate, DMSO, solvent free) on the activity and selectivity of the nanocatalysts has been noted [27][41][42][43][44]. Furthermore, all the reported methodologies use either molecular oxygen together with an aldehyde as a co-reductant, or only a “green” peroxide (H2O2, TBHP) as

• other hand, among the peroxide-free oxidation processes, a Co3O4/SBA-16 catalyst for the epoxidation of limonene in AcOEt [43] and a Co/HAP catalyst in DCM as the solvent [44] have been very recently reported. Both of these catalytic systems gave good conversions to the desired epoxides and allowed the