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

• on this feature to isolate biguanide as a copper complex. Interestingly, transition metal-biguanide complexes often present vivid colors because of a strong absorption in the visible range. Biguanides have been used in chemistry as versatile starting materials in organic synthesis, catalysts [5

• transesterification of several vegetable oils [5]. Since the first reported copper-biguanide complex, the synthesis of a variety of stable biguanide complexes has been reported with VIV, CrIII, MnIII, MnIV, CoII, CoIII, NiII, CuII, ZnII, PdII, ReV, OsVI [8], etc. Many of these complexes found applications as

• reagent to prepare biguanides dates back to the 1880s at the time of the first historical syntheses. During the decade following the biguanide discovery, three different techniques were investigated: a) the reaction of cyanoguanidine with an aqueous solution of an amine in the presence of copper salts [13

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

• -position of an oxazoline or amide is selectively activated using a copper or palladium catalyst. Manganese is one of the most abundant and nontoxic transition metals found in the earth’s crust and its corresponding complexes and salts are useful in synthetic organic reactions [29][30][31][32][33][34][35

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

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

• Meldal have independently developed a copper-catalysed azide–alkyne cycloaddition that accelerated the rate of the reaction and allowed the selective preparation of 1,5-disubstituted 1,2,3-triazoles [16][17][18][19]. As noted above, a wide range of methods are available in the literature for the

• 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

• anticancer drug vatalanib [26][27][28] (Figure 1). On the other hand, aminophthalazinones can be prospective candidates as N- and O-donor ligands to form complexes with biological significant metal ions, such as copper or zinc [29]. Recently, we have demonstrated a strategy for the synthesis of phthalazinone

• -bromobenzoate via palladium-catalyzed isocyanide insertion [32][33] (a method that is limited to tertiary-substituted isocyanides) or 2) the palladium or copper-catalyzed coupling of bromolactams with amines (a method that requires the usually lengthy synthesis of the bromoprecursors) [19][34]. Therefore, the

• 63Cu2+/65Cu2+ ion complex containing two ligands L2. However, a significant amount of unchanged ligand was also visible. For the ion at m/z = 719.5 Da, tandem spectra were recorded. The first fragmentation gave ions at m/z = 329.3 Da (L2 + H+) and 391.4 Da (ligand L2 and copper). The further

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• tetraacetate (Scheme 39) [60][61]. To develop novel bone-targeting prodrugs, a copper-catalyzed carbene insertion of tetraethyl diazomethyldiphosphonate (216) with N-Boc-protected amino acids 214 and 215 provided a simple method to synthesize phosphonodepsipeptides 217 and 218 containing a C-1

• -catalyzed carbene insertion. Synthesis of phosphonodepsipeptides with a C-1-hydroxyalkylphosphonate motif via a copper-catalyzed carbene insertion reaction. Funding The project was supported by the National Natural Science Foundation of China (Nos. 21772010 and 21572017).

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• -Dimethylformamide (DMF) was purified by a solvent-purification system (GlassContour) equipped with columns of activated alumina and supported-copper catalyst (Q-5) before use. 1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was distilled from molecular sieves 4 Å and stored over activated molecular sieves 4 Å. 1,4-Dioxane

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

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

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• chlorine at the purine C2 position by azide, and 3) copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) with different alkynes. Pathway B included: 1) the two-step synthesis of 2,6-bistriazolylpurine derivatives 6 from 2,6-dichloropurine derivative 1 [22] and 2) the SNAr–Arbuzov reaction with

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• structures modified with sulfate groups, and their capability to interact with biological components has been demonstrated recently [31][32]. In this work, we therefore coupled dPGS to C2-symmetrical discotic peptide amphiphiles using copper-catalyzed azide alkyne cycloaddition chemistry. The evaluation of

• , post-functionalization using a subsequent copper-catalyzed azide–alkyne cycloaddition reaction became accessible [35][36]. At the same time the other two unmodified side arms of the dendritic amphiphile make sure that the fidelity of the β-sheet motifs and directed supramolecular polymerization remains

• copper-catalyzed azide–alkyne cycloaddition (Scheme 2). The reaction took place in degassed DMSO at 50 °C with CuSO4 pentahydrate, sodium ascorbate and tris(benzyltriazolylmethyl)amine (TBTA) as chelating species. HPLC-monitoring of the reaction showed a full conversion after three days and the crude

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• synthetic efforts toward neooxazolomycin (4), oxazolomycin A (5a), and related antibiotics [17]. The recent review of Lee has mainly focused on the application of copper(I) salt and fluoride-promoted Stille coupling reactions in the synthesis of bioactive molecules including inthomycins A–C (1–3) [18]. The

• Stille coupling between oxazole vinylstannane 24 and dienyl iodide (rac)-20 as the final step. The synthesis began with alcohol (Z)-15a, which was readily prepared in 65% yield from propargyl alcohol (14) by using a copper(I)-catalyzed methyl Grignard addition followed by in situ iodinolysis. The Swern

• benzoate to give (−)-141 in good yield. Next, the benzoate-protected ynoate (−)-141 was converted into aldehyde (Z)-(+)-143a by employing a copper-catalyzed methylation of the alkyne moiety to the corresponding enoate (Z)-(+)-142 followed by an ester reduction–oxidation sequence using DIBAL-H and TPAP

Control over size, shape, and photonics of self-assembled organic nanocrystals

• Chen Shahar,
• Yaron Tidhar,
• Yunmin Jung,
• Haim Weissman,
• Sidney R. Cohen,
• Ronit Bitton,
• Iddo Pinkas,
• Gilad Haran and
• Boris Rybtchinski

Beilstein J. Org. Chem. 2021, 17, 42–51, doi:10.3762/bjoc.17.5

• were obtained. TEM TEM imaging was performed using a Tecnai T12 transmission electron microscope operated at 120 kV. Sample preparation: 8 µL of each sample was applied to a 400 mesh copper grid coated with carbon (on nitrocellulose support) and blotted 2 min later from the back side of the grid. Cryo

• microscope operated at 120 kV, using a Gatan 626 cooling holder and transfer station, with a TVIPS F244HD CCD digital camera. Sample preparation: 8 μL of each sample was applied to a 300 mesh copper grid coated with holey carbon (Pacific Grid-Tech supplies). The samples were blotted at 25 °C and 95% relative

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• in 65% yield and complete stereochemistry retention. When isocyanate (−)-84 was treated with copper chloride in water and THF, the (+)-euphococcinine (2) was obtained in 63% yield. A similar sequence was used to synthesize natural (−)-adaline (1, Scheme 10). In this case, vinyl iodide 86 was obtained

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• form the CF3Se–C(sp3) bond. This chemistry is the prerogative of the CF3Se− anion (Scheme 1) [37][38][39][40]. However, the formation of this selenium species requires the tedious use of red elemental selenium [41] and also suffers from stability issues. To circumvent these drawbacks, a copper complex

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tetracyclic compound 56. Dihydroxylation of freshly prepared 56 with OsO4 and then selective tosylation afforded 57 in 39% yield over two steps. Exposure of 57 to DBU upon heating gave the elimination product 58, which was subjected to an oxidative rearrangement with PDC to give enone 59 in 68% yield. Copper

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• a robust supporting material to immobilize a copper species. The so-obtained catalyst was characterized by many physicochemical methods including FTIR, EA, FSEM, FTEM, XPS, and TG. This catalyst exhibited excellent catalytic activity in the synthesis of nitrogen-containing heterocycles such as

• ; heterogeneous catalyst; immobilized copper catalyst; lignosulfonate; nitrogen-containing heterocycles; solid acid; Introduction Heterogeneous metal catalysts have been continuously receiving considerable attention in the field of organic synthesis owing to the advantages of easy separation and recycling [1][2

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• RNA in a highly selective and efficient way. The more traditional strategies rely on reaction of isothiocyanates or NHS esters with aliphatic amines [13][14], or on addition of thiols to the α,β-unsaturated carbonyl face of maleimides [15]. Over the past years, the copper catalyzed alkyne–azide

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• self-sorting protocols. The present mini review will provide an overview over the latest advancements in this field with a focus on reversibly switchable functions in discrete supramolecular systems. Keywords: copper; fluorescence; self-assembly; self-sorting; zinc porphyrin; Introduction Since self

• via metal ion translocation [56]. In detail, the addition of Zn(OTf)2 replaced copper(I) in nanoswitch [Cu(21)]+ with zinc(II), sending stoichiometric amounts of copper(I) ions as a second messenger to self-assemble the supramolecular rectangle or prism from ligands 22–24 (SelfSORT-II). Using

• transformation of one nanodevice into another [57], for instance, in the reversible interconversion of nanosliders within six and seven-component networks. Upon the addition of three equiv of zinc(II) ions to three equiv of the nanoswitch [Cu(25)]+ (Figure 11b), the equivalent amount of copper(I) was released

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• moderate yields (16–38%), mainly because of severe difficulties to completely remove the copper ions that apparently bind tightly to the compounds. The new compounds 4a–e were identified and fully characterized with NMR spectroscopy (1H, 13C, COSY, HSQC, HMBC), mass spectrometry, and elemental analysis

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• the corresponding stabilized anion [20] and is readily transformed into a hydroxy group by treatment with copper bromide according to our previous work [21]. Allylation of 2b with 1a at room temperature proceeded in the presence of a catalytic amount of Pd(PPh3)4 by using potassium tert-butoxide or

• the construction of the spiro skeleton of 4 and 5. For this purpose, we initially attempted to transform 3b to 5a through the reaction sequence consisting of copper-mediated hydroxylation and acid-mediated lactonization based on our previous reports [10][11][14][21]. Substitution of the phenylthio

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

Particle size effect in the mechanically assisted synthesis of β-cyclodextrin mesitylene sulfonate

• Stéphane Menuel,
• Sébastien Saitzek,
• Eric Monflier and
• Frédéric Hapiot

Beilstein J. Org. Chem. 2020, 16, 2598–2606, doi:10.3762/bjoc.16.211

• speed of 0.4°/min) using the Bragg–Brentano configuration. Scanning electron microscopy Scanning electron microscopy (SEM) images were recorded on a SEM JEOL JSM-7800F LV instrument at 3.0 kV. The powder was deposited on a carbon-coated copper grid. The particle size distributions were determined from

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

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• ; catalysis; copper; fluorine chemistry; trifluoromethylation; Introduction The introduction of a trifluoromethyl group is one of the most attractive reactions in drug discovery [1][2]. In the past decade, trifluoromethylation reactions of aryl halides in the presence of transition-metal complexes were

• recently reported the trifluoromethylation of iodoarenes by use of 2-aryl-2-trifluoromethylbenzimidazoline as the trifluoromethylating reagent in the presence of 3 equiv of a copper salt [22]. The benzimidazoline derivatives could be readily prepared from relatively cheap materials, namely

• , trifluoromethylacetophenone and phenylenediamine derivatives (Figure 1b). Herein we report a catalytic trifluoromethylation of iodoarenes by use of benzimidazoline derivatives in the presence of a catalytic amount of copper salts and a bipyridyl ligand (Figure 1c). Results and Discussion We first investigated the reaction