Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• , three-component procedure was also explored for the preparation of 3-aryl-4H-benzo-1,4-thiazin-2-amines [18]. 3-Aryl- and 3-alkyl-4H-benzo[b][1,4]thiazine-4-carbonitriles 2 (Figure 1) were synthesized in high yield from the corresponding 2-aminobenzothiazoles using the copper–organic framework Cu–MOF-74

• -3(4H)-ones were also prepared by cyclization of 1,2-diaryldisulfanes with dialkyl but-2-ynedioates [24][25]. N-Substituted benzo-1,4-thiazine-2-carboxylates 4 (Figure 1) were prepared by m-CPBA-mediated oxidative ring expansion of substituted benzothiazoles [26], or via copper-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

• nitrogen-enriched quinoxaline-based structures. Literature-known procedures for such a quinoxaline modification starting from tetrazolo[1,5-a]quinoxalines 1 are the synthesis of 1,2,3-triazoloquinoxalines 3 via copper-catalyzed azide–alkyne cycloaddition (CuAAC) [10] and the synthesis of imidazo[1,2-a

• 1,2,3-triazoloquinoxalines 3 and imidazo[1,2-a]quinoxalines 2 under conditions known for copper-catalyzed azide–alkyne cycloaddition (CuAAC) [10]. The currently published porphyrin-catalyzed process requires glovebox conditions and the use of an expensive catalyst [11]. We intend to elucidate the

• reactions and denitrogenative annulation according to Roy et al. [11]. Copper-catalyzed azide–alkyne cycloadditions are initiated via the (dual) complexation of the alkyne, whereas denitrogenative annulation on 1,2,3,4-tetrazoles is assumed to start via complexation of the open-form azide 18 (see Scheme 4

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

• de Caxias do Sul, 95070-560, Caxias do Sul-RS, Brazil 10.3762/bjoc.18.110 Abstract The broad application of 1H-indazoles has prompted the development of several approaches for the synthesis of such compounds, including metal-free, palladium-, or copper-promoted intramolecular N-arylation of in situ

• available and less expensive than brominated analogs. Seeking to cover a lack in the literature, this work reports a convenient protocol for the synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of o-chlorinated arylhydrazones. Therefore, a series of seven N

• . All products were fully characterized by HRMS as well as 1H and 13C NMR spectroscopy. Thus, this approach is valuable for promoting the synthesis of N-phenyl-1H-indazoles in a higher yield than that reported in the literature using copper catalysis and the same substrates. This study also prompted the

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• electrochemical reactor. C/PVDF anode before (A) and after (B) the first experiment (Table 1, entry 1). Expanded view of the electrochemical cell components: (a) Aluminium end plates; (b) insulating PTFE foil, (c) copper plate for electrical contact; (d) carbon electrode; (e) PTFE gasket (reaction channel and

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• aqueous lithium hydroxide, THF, 4 h, 94% [15]; e) copper powder, quinoline, 230 °C, 1 h, 81% [15]; f) N-bromosuccinimide, CHCl3/glacial acetic acid, 0 °C, 1 h, rt, 1.5 h, 94% [15] ; g) n-BuLi, −90 °C, 20 min, triisopropyl borate, −80 °C, anhydrous THF, rt, overnight, 97% [34]; h) pinacol, toluene, 115 °C

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -oxides 42 and 44 in moderate 54–63% yields via the intramolecular copper-catalyzed cross-coupling of ethyl/benzyl 2-bromobenzylphosphonamidates 41 or P-(2-bromobenzyl)-P-(methyl)phosphinamide (43) as a key step. They were prepared from 2-bromobenzyl bromide (38) via three and four steps, respectively

• 105 via the copper-catalyzed intramolecular carbene aromatic C–H bond insertion (Scheme 20) [44]. This is an efficient synthetic strategy for 3-benzoyl-2-ethoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 106 through the formation of the C–C bond neighboring at the ring phosphorus atom. Synthesis

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• –Prakash reagent (TMSCF3) in the presence of Cs2CO3 as base in MeCN at 0 °C gave product 7 with a trifluoromethyl group. Stefani et al. reported the 1,3-dipolar azide–alkyne cycloaddition (AAC) of organotellanyl alkynes with organic azides in the presence of a copper reagent to form 5-organotellanyl-1,2,3

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• Shao-Cong Zhan Ren-Jie Fang Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.18.80 Abstract In the presence of copper sulfate, three- or four-component reactions of 2-methylindole, aromatic aldehydes and various cyclic

• this respect, Lévy reported a copper-catalyzed three-component reaction of aromatic aldehydes, ethyl indole-2-acetate and N-alkylmaleimides for the efficient construction of polycyclic tetrahydrocarbazoles, in which indolo-2,3-quinodimethane intermediate was initially generated and sequentially

• -known 3,3'-(arylmethylene)bis(2-methylindoles) 6. Conclusion In summary, we have developed a copper-catalyzed multicomponent Diels–Alder reaction of 2-methylindole, aromatic aldehydes and cyclic 1,3-diones through in situ generated dienes and dienophiles under the same conditions. These strategies are

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• was replaced by the Zn/Cu couple which was prepared without any metal activation by in situ ball milling of zinc and copper dusts. The advantage of the ball milling process is that the whole procedure is operationally very simplified. The reactive alkene generated was trapped in situ by several dienes

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

• heating has also been used for bonding, heating rubber, deforming plastic, or shrinking workpieces [13][14][15]. These materials are not conductive like steel, copper, or alloys, so another mechanism must take hold to introduce heat. This is often achieved by embedding small superparamagnetic

• further catalyzes this reaction, complete conversions with low carbon formation could be obtained at low flow rates. At higher flow rates, reaction kinetics was the limiting factor. Later, it was found that by doping the alloy with small amounts of copper, almost complete conversion (95%) could be

• enable rapid heating of inductive materials such as steel or copper, or fixed-bed materials composed of steel beads as well as superparamagnetic nanoparticles in an oscillating electromagnetic field. Kirschning and co-workers introduced nanostructured particles based on Fe2O3/Fe3O4 coated with silicon

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• the amidyl radical precursor under air is reported. A possible mechanism is proposed that proceeds via a radical reaction in the presence of CuBr and triethyl phosphite. Keywords: amination; copper; N-hydroxyphthalimides; radical reactions; triethyl phosphite; Introduction Practical methods for

• (reaction 3) [27]. Herein, we report a method for the construction of aromatic amines via the copper-catalyzed intermolecular radical amination of arenes with N-hydroxyphthalimide (NHPI) under air. Results and Discussion Initially, N-hydroxyphthalimide (NHPI, 2a) was reacted with benzene, catalyzed by CuBr

• (40 mol %) in the presence of P(OEt)3 (6 equiv, triethyl phosphite) under air at 100 °C (Table 1). The yield of the corresponding amide 3a was 78% (Table 1, entry 1). The reaction was completely inhibited in the absence of the copper catalyst or P(OEt)3, and no product was detected (Table 1, entries 2

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• metal–ligand motifs often center about iridium, ruthenium, rhodium etc. [25], the dynamic ones are constructed using copper(I), zinc(II), cadmium(II), iron(II), palladium(II), etc. as metal ions due to their more rapid ligand exchange rates [24][25][26]. The strategies to prepare inert vs dynamic

• , since a variety of heteroleptic aggregation protocols have been developed by Schmittel [37] (for copper(I), zinc(II), cadmium(II), mercury(II) ions) and Yoshizawa/Fujita [38] (for palladium(II) ion) that involve pyridine-derived ligands. Highly innovative are the approaches for terpyridine-based

• . Accordingly, the distinct zinc porphyrins 55 and 57 were positioned at a defined distance through two NDABCO → ZnPor interactions. Clearly, without additional measures, homo- and heteromeric assemblies would form. However, due to the additional HETPYP interaction(s) in the presence of copper(I) ions

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• 90% acetonitrile with 0.1% formic acid and 10% water with 0.1% formic acid at a flow rate of 0.4 mL/min. Freeze-drying was conducted on a Scientz-18N freeze-dryer. Synthesis of compound 2. A mixture of compound 1 (2.30 g, 3.7 mmol), ethyl azidoacetate (5.76 g, 44.7 mmol), copper(II) sulfate

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• treated with copper iodide to obtain the phenanthroline–Cu(I) complex (R)-8. A Glaser-type coupling with the terminal alkynes 9, followed by demetalation, proceeds smoothly in 78% yield. This furnishes the desired chiral rotaxane (R)-10, consisting of a BINOL-based macrocycle and a diyne thread. The CD

• ]. Macrocycle (S)-61, featuring two iodotriazole units, was reacted with bis-iodoalkyne 62 and azides 63a/b in order to establish the mechanical bond in an active metal template approach (using the conformational flexibility of the iodotriazole groups for copper N-ligation). Subsequent N-methylation of the

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• the simplicity of the method, we chose the Liebeskind–Srogl cross-coupling reaction for the synthesis of the target 2-arylpyrimidine derivatives. Thus, heating tCbz-mPYR with phenyl-, 4-cyanophenyl-, 3-cyanophenyl-, or 3-bromophenylboronic acid at 130 °C in dioxane in the presence of Pd(PPh3)4, copper

• equiv; 1 equiv in case of meta-substituted boronic acids), copper(I) 3-methylsalicylate (2.2 equiv), dioxane, 130 °C, 4 h, argon; iii – oxone (2.5 equiv), DMF, 80 °C, 3 h; iv – NaCN (2.2 equiv), THF, reflux, 3.5 h; v – 4-t-BuC6H4SH (1.1 equiv), Et3N (1.1 equiv), THF, 50 °C, overnight, argon. DFT

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• alkynes to activate them for a decent yield of the isoxazole products, thus limiting the scope of the substrates in this method. In addition, this method requires high heat and produces very poor regioselectivity of the products [17][18]. The addition of copper catalysts in this route can help the

• highly substituted non-terminal alkynes does not proceed with copper catalysts at room temperature. As an alternative, the usage of ruthenium(II) catalysts enables the reaction to proceed smoothly at room temperature and produces high yields and regioselectivity for both, 3,5-disubstituted and 3,4,5

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• highly efficient catalysts based on copper complexes of different types of chiral ligands, 2-(pyridin-2-yl)imidazolidine-4-ones (I–III), bis-oxazolines (IV–VII), or diamine (VIII) were chosen for the study (Figure 2). Furthermore, the modification of the structure of the prochiral aldehyde intermediates

• catalysts based on copper(II) complexes with chiral nitrogen ligands were chosen. Generally, chiral copper complexes possess many advantages valuable for the pharmaceutical industry. They exhibit low toxicity (compared to other metal-based complexes) and many of them exist in forms suitable for recycling

• [19]. Therefore, they represent a very useful tool for diverse asymmetric transformations, including the Henry reaction. The pilot study of the synthesis of rivaroxaban through an asymmetric Henry reaction [12] described the application of only one copper complex with a 2-(pyridin-2-yl)imidazolidin-4

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

• and co-workers performed a bismuth catalyst system study for the methylation and alkylation of quinone derivatives [84]. Furthermore, they also evaluated the methylation without catalysts and with the use of lanthanum(II) and copper(II) salts as additive. However, the best results were achieved with

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• intramolecular transformation [14], the insertion of a boron atom into chiral oxindoles is scarcely reported. Continuing with such previous project, next we looked at the copper-mediated reaction of isatin-derived, optically pure sulfinyl ketimines with bis(pinacolato)diboron, as a potential way to access

• of water to the minimum necessary to solubilize the copper sulfate. Thus, performing the reaction in toluene/water 100:1, ketimine hydrolysis was almost entirely prevented and the yield of compound 2a raised to 52% (Table 1, entry 6). With regard to the ligand (Table 1, entries 7 and 8), PPh3 behaved

• most effectively, further promoting the conversion of the substrate. Other changes in reaction conditions, such as heating at 70 °C, increasing the amount of copper catalyst to 10 mol % and switching the copper salt from CuSO4 to the more soluble Cu(OTf)2, did not improve the yield significantly (Table

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• –Spengler-like cyclization processes [12]. Some 4-substituted 3,4-dihydroquinazolines were prepared by copper-catalyzed oxidative cross coupling of hydroxy intermediates with various nucleophiles [13]. Other 3,4-dihydroquinazolines were also obtained efficiently by intramolecular aza-Wittig reactions [14

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• importance of this coupling reaction [7]. Later, Sonogashira-type reactions requiring only copper as catalyst alone [8] and with other transition metals [9][10][11][12] have been reported. Especially iron has attracted a great deal of attention owing to its low price, easy availability, abundant nature, and

• /hydroalkoxylation of alkynes was also reported (Scheme 8). Vogel and co-workers demonstrated the Sonogashira cross-coupling reaction of aryl iodides with terminal alkynes by utilizing cheap, non-toxic iron salts and copper iodide (Scheme 9) [26]. The reaction of 4-iodotoluene with phenylacetylene was chosen as the

• dendrimers were grown on graphene nanosheets for catalyzing the reaction using highly active Pd-Co bimetallic nanoparticles under copper and solvent-free conditions at room temperature. K2CO3 was found to be the suitable base which provided a relatively good yield (Scheme 28) [41]. The graphite sheets could

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• sialic acid derivatives in good yields and high purity via copper-catalysed azide–alkyne cycloaddition (CuAAC, click chemistry) and evaluated their activity towards TcTS and neuraminidase. Surprisingly, the compounds showed practically no TcTS inhibition, whereas ca. 70% inhibition was observed for

• ) has also been introduced at C-2 of α-triazole-linked sialic acid derivatives modified at C-9 as ligands for the transmembrane glycoprotein CD22 [21]. In this sense, we have synthesised a small series of 1,2,3-triazole-linked sialic acid derivatives via copper-catalysed azide–alkyne cycloaddition

• 3a–h via copper-catalysed azide–alkyne cycloaddition (CuAAC) from the key intermediate 1 (B). TcTS and neuraminidase hydrolase activity (A) as well as TcTS transferase activity (B) in the presence of an acceptor substrate. TcTS and neuraminidase inhibition by 1,2,3-triazole-linked sialic acid

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• copper(II) complexes prepared revealed an enhanced aqueous solubility and bioavailability indeed, along with very high cytotoxicity [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Moreover, the metal-free ligands and copper(II) complexes derived from backbone D revealed cytotoxicity 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

• industries as one of the most powerful methods for molecular assembly. With regard to the cost of goods and the allowance of trace metal impurities in medicinally relevant compounds, 3d transition metal complexes, such as those of iron, copper, cobalt or nickel, represent exciting, more sustainable

• proximity-induced C–H functionalizations. In this thematic issue, strategies are presented that guarantee position-selectivity in copper-mediated isoindolin-1-one synthesis [12] as well as in copper-catalyzed aminations of ferrocenes [13]. The exploitation of the innate reactivity of organic molecules can

• 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

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• ) provide entry into similar photo-uncaging chemistries for amide release. Figure 1C shows an example of this concept applied to a peptide substrate. Reaction of the peptide i with an alkenylboronic acid reagent iv in the presence of a copper(II) salt in water provides access to the backbone N–H