Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• example, based on N-containing heterocycles (isoxazolones, pyrazolones, pyrazolidin-3,5-diones, and 1,2,3-triazolones [52]), sulfones [65], and phosphonates [54] (Scheme 8). Based on the data of EPR spectroscopy [35][38][49][50][66] and quantum chemical calculations [67], the maximum spin density in

• or 61). As a result of the reaction, a 5-membered cycle is formed via the formation of C–O (products 58 and 60) or C–N bond (product 61) in accordance with the ability of oxime radicals to act as O- or N-radicals. The formation of the heterocycles, mainly isoxazolines/isoxazoles, from unsaturated

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• related to natural products [18][19][20]. Among the well-established MCRs, three-component 1,3-dipolar cycloadditions of benzaldehydes, maleimides, and amino esters have been developed for making N-containing 5-membered heterocycles (Scheme 1) [21][22]. The [3 + 2] cycloadditions of maleimides with

• pyrrolidines II-b was less explored [27][28][29]. In recent years, our lab has reported a series of 1,3-dipolar cycloaddition-initiated methods for the synthesis of diverse heterocycles A–J bearing fused polycyclic rings such as tetrahydroepiminobenzo[b]azocines, tetrahydropyrrolobenzodiazepinones

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• influence the yield of the materials. Thermally stable benzene moieties increase significantly the amount of carbon material produced, whereas mixtures based on amines or heterocycles decrease the yields [77]. The salt templating method developed of Antonietti and co-workers produces carbon materials with

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• -Acr+ scaffold. In 2015, they developed a site-selective C–H amination of arenes (Scheme 25) [110]. The arenes 25.1 could be aminated by various N-heterocycles 25.2 for the synthesis of the C–H functionalization products 25.3 with fine-tuned Mes-di(t-Bu)Acr+ (OD4) as a photocatalyst. In this

• oxidation of 29.1 was achieved using Mes-Acr-Me+ (OD2) and a cobalt cocatalyst, ensuring an efficient dehydrogenation. Various N-heterocycles 29.3 were accessed via a radical cyclization cascade with the alkyne derivatives 29.2. Amidyl radical generation The oxidation of amides is more difficult compared to

• previously described approach for iminyl radical formations was employed [140]. The same tunable aryloximes 31.1 were used as electrophores to generate the desired amidyl radicals. This methodology allowed the development of a hydroamination/cyclization cascade to give the heterocycles 31.2 and

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

• Dragana Vuk,
• Irena Škorić,
• Valentina Milašinović,
• Krešimir Molčanov and
• Željko Marinić

Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96

• for biological testing. Conclusion From the two starting thiophene derivatives 1 and 2, ten novel products 3–12 have been prepared by a simple and low-cost procedure, paving the way to new researches, some of which could be directed toward inclusion of new heterocycles. Due to their indicative

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• active small molecules that exhibit antihypertensive activity [7][8]. Moreover, these heterocycles can be used as 5-HT3 antagonists [9], rho kinase inhibitors [10], thymidylate synthetase inhibitors [11], PARP-1 inhibitors [12], melatonin MT1 and MT2 receptor agonist [13], and fascin-targeted

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• activity toward various cancer cell lines and relatively low cytotoxicity toward noncancer cells, suggesting that the diselenide 2f may potentially be an anticancer therapeutic drug. The application of this reaction to other heterocycles, as well as detailed studies into the C–H selenation and anticancer

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• heterocyclic ring, while the second part deals with acceptors in which the reacting unsaturated double bond is located outside of the heterocyclic unit (e.g., alkenyl-substituted heterocycles). The organometallics discussed in this minireview include organoaluminium, organozinc, organozirconium, organolithium

• reagents and protecting groups were examined, providing the products with good yield (up to 90%) and ee (up to 95%). Copper-catalysed conjugate addition reactions to alkenyl-substituted heterocycles Chiral heterocyclic aromatic compounds are crucial motifs in natural products and bioactive molecules, and

• asymmetric additions to N-heteroaromatic alkenyl compounds are less developed. This deficiency is largely due to the intrinsically low reactivity of alkenyl-substituted heterocycles towards nucleophilic addition compared to common Michael acceptors. A way to lift this barrier was introduced in 2016 by

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• involves energy transfer to surrounding molecules, such as molecular oxygen, heterocycles and other relevant molecules [15][16][17]. The excited states of porphyrins are also both potent oxidants and reductants when compared to the ground state. This phenomenon can be measured by the comparison of the

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• with TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl) [25] and ABNO (9-azabicyclo[3.3.1]nonane N-oxyl) radicals [26]. Later reports enlarged the synthetic scope of this methodology and provided access to a wide range of synthetically useful building blocks such as substituted heterocycles, fluorinated

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• ]. Among the P-heterocycles with various ring size, the five-membered derivatives received special attention due to their optimal bond angles and shapes [13][14]. Besides their application as ligands [13][15], the five-membered heterocycles may also be valuable organocatalysts in reactions involving a P

• importance for biologically active compounds, as specific functional groups are necessary to have a desired biological activity. Considering the functionalization of the five-membered P-heterocycles, the derivatives containing double bond(s) (i.e., phospholenes or phospholes) are of special importance, as a

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• hydroxyalkylation of indole. Structures of heterocycles that did not react with ketone 2a. Recyclability of the catalytic system n-Bu4PBr/K2CO3 for the preparation of 2,2,2-trifluoro-1-(5-methoxy-1H-indol-3-yl)-1-phenylethan-1-ol (3a). Gram-scale synthesis of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-phenylethan-1-ols

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• excellent E:Z ratios within the resulting alkenes. This methodology could be applied to a wide variety of compounds, including those containing heterocycles (176–178). In a later study [67], they found that by changing ligands, a dramatic switch in the selectivity could be induced in silyl additions to

• could be isolated (Scheme 34). Another class of heterocycles, α-silylated N-alkylated indoles 201–205 recently reported by Xu and co-workers, were formed using a nonracemic Cu–NHC catalyst through the enantioselective addition of the PhMe2Si group to α,β-unsaturated carbonyl indoles 200 (Scheme 35). The

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• has the potential to produce a large number of tetramic acid analogues, which cannot be easily accessed by the classic synthetic methods. Keywords: Dieckmann cyclization; multicomponent reactions; nitrogen heterocycles; one-pot reaction; Ugi reaction; Introduction Nitrogen-containing heterocycles

• chemistry [2][3][4]. Notably, one of these nitrogen-containing heterocycles is tetramic acid which contains a pyrrolidine-2,4-dione moiety. Many natural products have this key structure moiety (Figure 1) [5][6][7]. Because of their active cyclic keto-enol structure, the heterocyclic tetramic acid compounds

• [35][36][37]. These new processes improved the overall efficiency with shorter reaction times and lower costs of synthetic preparations, and minimized the amount of waste generated. In recent years, we used the Ugi four-component reaction as a main tool to generate nitrogen-containing heterocycles [38

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• strategy in the synthesis of a series of CH2SCF3-substituted heterocycles. For the construction of SCF3-substituted cyclic compounds, normally proper alkynes are chosen as the substrates for cascade reactions [28][29][30][31][32]. In 2015, Wang developed an oxidative radical cyclization of aryl alkynoate

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• or fluoroalkyl groups into three-membered N-heterocycles has emerged as an attractive direction due to the unique fluorine effect in pharmaceuticals and biology [7][8][9][10][11]. In this context, it is not surprising that the syntheses of trifluoromethylaziridines have been pursued from versatile

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• docking values were on par with that of the parent molecule, panobinostat (Figure 1). Given that the diazine-containing compounds are considered to be one of the most important classes of heterocycles, their presence in a plethora of pharmacology and drug molecules motivated us to synthesize these

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• BODIPY core has not yet been achieved. Inspired by the works of Waser and co-workers showing the gold(I)-catalyzed C–H electrophilic alkynylation of various heterocycles (e.g., pyrroles, indoles, etc.) with ethynylbenziodoxolone (EBX) as an activated ethynyl synthon [38][39][40][41][42], we investigated

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• catalysts; Sharpless–Meldal C–N bond-forming reaction; silica/carbon/magnetic materials; Introduction Heterocycles are a class of organic compounds with significant biological activities [1][2][3][4][5][6][7][8][9][10], including antimicrobial [2], antibacterial [3], anti-HIV [4], antiviral [5

• 100 °C for one day, cooled, and filtered. The material Pd–Cu@rGO (78), as heterogeneous nanocatalyst, was prepared by anchoring Pd(OAc)2 on Cu@rGO in toluene via pyrolysis. The catalyst was highly active in one-pot condensations of alkyl/aryl-substituted triazole heterocycles with cycloadditions and

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• compound from selenium dihalides was the preparation of 1,4-selenasilafulvenes by cyclization reaction with diethynyldimethylsilane [15][16]. The creation of new methodologies for the synthesis of new classes of organoselenium compounds and especially selenium heterocycles, with promising biological

• ][24][25][26][27][28][29]. Among these is an elegant, highly effective approach that led to β-hydroxy, β-mercapto, and β-amino-substituted diorganyl diselenides and selenides. This was accomplished by the opening of three-membered oxygen-, sulfur- and nitrogen-containing heterocycles under the action

• ]. Having established the synthesis of heterocycle 4 this unsaturated five-membered S,Se-containing compound was used as a starting material for the synthesis of novel ensembles of selenium heterocycles with promising biological activity. The treatment of 4 with organyl halides resulted in the efficient

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• yields often >80%. Keywords: amidation; DBU; folate; pterin; Introduction Pteridines are a class of fused bicyclic heterocycles with significant biological relevance. The 2-amino-4-pteridinone core, simply referred to as “pterin”, is present in various biological cofactors like folates, biopterin, and

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• coordination chemistry, and also valuable protecting or directing groups in catalysis [1][2][3]. 2-Oxazolines are a readily stable class of heterocycles resistant to a range of nucleophiles, bases, or radicals [4][5], which can be easily generated from amino alcohols and carboxylic acids, and from alkenes or

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• reaction was excellent as bromides, phenols, thioethers, esters, boronic esters, and heterocycles, including pyridine and quinolines, were well tolerated. The authors carried out mechanistic studies and demonstrated the H-bonding ability of their catalyst by NMR studies. The following mechanism was

• )(dap)2]Cl. Trifluoromethyl methoxylation of styryl derivatives using [Cu(I)(dap)2]PF6. All redox potentials are reported vs SCE. Trifluoromethylation of silyl enol ethers. Synthesis of annulated heterocycles upon oxidation with the Sauvage catalyst. Oxoazidation of styrene derivatives using [Cu(dap)2

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• heterocycles; fluorine; pyrazoles; pyrimidines; Introduction Due to its extremely widespread application in virtually all areas of synthetic organic chemistry, fluorine is considered a “magic” element. It confers metabolic stability and other unique properties to organic molecules and a large fraction of

• emtricitabine [30] (ingredient of Truvada®) and capecitabine [31] (Xeloda®) (see Figure 1) [32][33]. While the introduction of fluorine into preexisting heterocycles can require difficult-to-handle, expensive and highly corrosive electrophilic fluorine species [16][34][35], the present approach employs a

• the formation of fluorinated heterocycles. While attempts to obtain an aminooxazole upon reaction with hydroxylamine were unsuccessful, substituted hydrazines turned out to provide moderate yields of fluorinated pyrazoles. Phenylhydrazine (12a) was chosen as the model substrate for optimization (Table

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• -heterocycles. This discussion seeks to paint a broad picture and consolidate different synthetic protocols and techniques for N-heterocyclic phosphine motifs. The introduction provides an account of P,N-phosphine ligands, and their structural and coordination benefits from combining heteroatoms with different

• from α-C–H bond activation in heterocycles The α-position to a heteroatom in a cyclic compound is activated because of the difference in electronegativity with carbon. This presents an opportunity to readily generate organometallic nucleophiles. Chelucci et al. [71] used this fact to synthesize the

• three metal-centered chiral elements which are conferred upon coordination with a metal [121]. Conclusion In this review, the diversity of phosphine N-heterocyclic ligands and the variety of phosphine skeletons, which includes different five- and six-membered heterocycles and different coordinating