Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• asymmetric conjugate addition. The magnesium enolates 56 then participated in a copper(II)-mediated intramolecular oxidative coupling to afford benzofused spirocyclic cycloalkanones 57 (Scheme 14) [45]. Our team became interested in domino reactions of metal enolates generated by Cu-catalyzed asymmetric

• basis for generating and trapping of reactive metal enolates. The conjugate addition of R3Al to cyclic enones catalyzed by a combination of copper(II) naphthenate (CuNaph) and SimplePhos ligand L19 led to the corresponding aluminum enolates. Alexakis and co-workers used these enolates in a Mannich-type

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• . First, copper and zinc derivatives of the porphyrin-coumarin conjugates 11a–20a were synthesized in excellent yields by the click reaction between copper(II)-2-azido-5,10,15,20-tetraphenylporphyrin (4) or zinc(II)-2-azidomethyl-5,10,15,20-tetraphenylporphyrin (5) and various alkyne-substituted coumarins

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

• polyene 14 (prepared in two steps) in multigram quantities [23]. The reaction employed a divided cell with substoichiometric amounts of magnesium(II) acetate (0.5 equiv) and catalytic copper(II) 3,5-diisopropylsalicylate (0.02 equiv) to allow the redox radical cyclization of polyene in 42% yield. A Tsuji

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

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

• 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

• enantioselectivity was achieved with the copper(II) complexes of ligands Ia, IIa, IIIa, and IV. Fortunately, these catalysts provided the R-enantiomer of nitroaldol 21 as the major product, which can be subsequently transformed to S-linezolid (1) (the active stereoisomer). On the other hand, the catalysts derived

• corresponding nitroaldol 22 by the action of the complex Cu(OAc)2/Ia with practically identical de of 88%. On the other hand, the interpretation of chemical yields is rather indistinct. Generally, the copper(II) complexes of ligands Ia and IV exhibited a higher catalytic activity than the catalysts derived from

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

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

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

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• conversion of 3 into the cyclohexanone product 4 (Figure 2) [4]. The best results were obtained with 2-[4-(S)-tert-butyloxazolin-2-yl]pyridine ((S)-5), which gave >90% yield of (S)-4 in 46% ee. In a similar investigation except with copper(II) as the metal and β-hydroxy-α-diketone 6 as the substrate, the

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• [40]. BPNs were tested as NIR photoinitiator for the CuAAC reactions of low molar mass compounds and polymers possessing antagonist azide and alkyne functionalities (Figure 1). The optical absorption spectra of BPNs, copper(I) chloride (CuICl, 0.05 mmol) and copper(II) chloride (CuIICl2, 0.05 mmol

• phenylacetylene (Alk-3) in the presence of copper(II) chloride/ N,N,N’,N’,N’’-pentamethyldiethylenetriamine (CuIICl2/PMDETA) and exfoliated BPNs under the white LED irradiation was performed (Figure 3). The reaction was followed by 1H NMR spectroscopy during the click process. The decrease of the acetylene proton

• ’’-pentamethyldiethylenetriamine (PMDETA, Aldrich), sodium azide (NaN3, Panreac), copper(II) chloride (CuIICl2, Merck), black phosphorus, dimethyl sulfoxide (DMSO) was used as received. Propargyl acrylate (Sigma), styrene (Merck) were purified before by using a basic alumina column to remove the inhibitor and then stored in 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

• standard conditions. The proposed catalytic cycle included aza-Michael addition of arylamines, Lewis acid copper(II)-catalyzed intramolecular 5-endo-dig cyclization, protonation, and oxidation to provide the final products, tetrasubstituted pyrroles 39. The introduction of a trifluoromethyl group into

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• , iron(III) chloride hexahydrate, trifluoroacetic acid (TFA), N-trifylphosphoramide (NTPA), benzoic acid, diphenyl phosphate (DPP), malonic acid, chloroacetic acid, copper(II) triflate, acetic acid, and p-toluenesulfonic acid (p-TSA) were used as catalysts. TFA gave the best yield of these catalysts with

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• carboxylate-assisted C−H cleavage to deliver copper(II) intermediate A. Next, the copper(III) carboxylate species B is generated. Thereafter, a facile base-assisted ligand exchange is followed by reductive elimination to afford the alkynylated benzamide D. Finally, the desired isoindolone 3 is formed via an

• intramolecular hydroamination in the presence of base. Conclusion In conclusion, we have reported on the chelation-assisted oxidative copper-promoted cascade C−H alkynylation and intramolecular annulation. The removable N-2-pyridylhydrazide was utilized to facilitate copper(II)-promoted C−H activations. Thus

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

• and aromatic amines. Being free amines aliphatic amines reacted better with arylcyanoguanidine in the presence of excess copper(II) salts in aqueous ethanol, whereas aniline derivatives were more prompt to react as hydrochloride salts in a suitable high boiling point solvent. The reaction with copper

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• an easy pathway to synthesize such triazolylenones. Inspired by this result, we proceeded to optimize the reaction conditions to further improve the yield. Replacement of rhodium by copper (II) acetate slowed down the reaction with a marginal change in the yield of the product 3a (Table 1, entry 2

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• the coordination of copper(II) through nitrogen atoms of the pyridin-2-yl substituent, the pyridazin-3-one moiety, and the 2-(dimethylamino)ethyl group. In the vis–NIR spectrum recorded in methanol, based on TD-DFT calculations, the d–d, metal–ligand charge transfer (MLCT), ligand–metal charge

• compound moiety. Based on the results of X-ray structural analysis of the Cu(II) complex with 7, it can be assumed, that also in the case of ligand 5i (L2) the nitrogen atoms of the pyridin-2-yl and azomethin moiety participate in the coordination with Cu(II) ions. Crystallography of complex 17 The copper

• (II) complex 17 [(L3)Cu(II)Cl2] was synthesized and characterized by X-ray analysis, FTIR and vis–NIR spectroscopy (for details see Supporting Information File 2). The molecular structure of the complex 17 is shown in Figure 4 and Figure 5. The basic experimental details and selected crystallographic

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• to prepare α-thiocarbonyl compounds. In this way, Bolm and collaborators elaborated a copper(II) acetate-catalyzed reaction of β-dicarbonyl compounds with diaryl disulfides (Scheme 1A) [50]. In 2017, Zou and co-workers described the preparation of α-thiocarbonyl compounds through a reaction of 1,3

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• anion concentration [31]. Similar effects were achieved by using a tripodal copper(II) complex as the external crosslinker [32][33]. Finally, the metal ion-induced aggregation of AuNPs containing DPA residues in chloroform or acetonitrile/water was reversed by the addition of diphosphate anions (which

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• -2,3,4,6-tetraacetylglucose (1.48 g, 3.96 mmol), copper(II) sulfate pentahydrate (52 mg, 0.21 mmol), and sodium ascorbate (28 mg, 0.14 mmol) in tetrahydrofuran/water cosolvent 2:1 (10 mL, v/v) was stirred vigorously under nitrogen in the dark at 60 °C for 24 h. Then, the solvent was removed under reduced

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• the catalyst SiO2@H3PW12O40 [21], the reaction of tetracarbonyl compounds with o-aminothiophenol (1a) [22][23], the reaction of copper(II) chelate of ethyl pentafluorobenzoylpyruvate with o-aminothiophenol (1a, one example) [24] and the reaction of DMAD with 6-nitro-1,3-benzothiazole (one example) [25

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• , base, and temperature on the course of the CEL arylation in the presence of copper(II) acetate monohydrate (Table 1). As observed for dichloromethane medium, the reaction proceeded very efficiently, with a product 3a yield of 88%, and reached completion within 48 h upon the addition of 2 equiv of

• replacement of pyridine by other organic bases/ligands (4-DMAP, 2,2’-bipy, Et3N, TMEDA, 8-hydroxyquinoline) resulted in poorer yields of the target product in all cases (Table 1, entries 6–10). The use of copper(II) fluoride (in contrast to triflate) instead of acetate had practically no effect on the

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

• Cu(ClO4)2 afforded a better yield of the C–O coupling product 48 then the manganese-based oxidants in this case (Scheme 17) [94]. A radical mechanism was suggested. The copper(II) ion reacts with oxime 19 to generate iminoxyl radical 20 and also forms complex 49 with dinitrile 47. Interaction of

• -position (R1, R2 = Me), as well as oximes having a disubstituted double bond, also give cyclization products with good yields (products 152b,c). The interaction of β,γ-unsaturated oximes 153 with sodium sulfinates in the presence of copper(II) acetate leads to substituted isoxazolines 154 with the sulfonyl

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• (purchased from Aldrich), 9H-carbazole, copper(II) chloride (purchased from Reakhim), and 2,7-di-tert-butyl-9,9-dimethyl-9,10-dihydroacridine (purchased from Center for Physical Sciences and Technology) were used as received. Thin-layer chromatography was performed using TLC plates covered with silica gel

• solid sample of compound 1 (e, inset). Synthesis of quinazoline derivatives 1–3. Conditions: i) ammonium acetate, copper(II) chloride, isopropanol, reflux, 24 h; ii) donor moiety (D), NaH, DMF, reflux, 24 h. Electrochemical characteristics. Photophysical properties of compound 1–3. Funding This project

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

• % ee (22c, Scheme 7A) [31]. The research group of Alexakis was able to push this chemistry further when they developed a new methodology that allowed to access the chiral lactams 26 with moderate yield and high enantioselectivity (up to 96% ee). Therein, the copper(II) naphthenate/L5-catalysed ACA of