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

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

• complexation to the Lewis acid in RCA reactions, an auxiliary (Z) is required; this auxiliary can be easily removed and recovered. Shibasaki and Kumagai very recently developed a similar reaction using a copper Lewis acid catalyst and a different auxiliary containing amide 282 with α-silyl amines 277 to

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

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• of 6 with an excess of known (see Supporting Information File 1) dialkyne 10 under several of the most common conditions produced triazole 11 in only modest yields (Scheme 2). The best conditions involved using Cu(MeCN)4PF6 as the copper(I) source, tris(2-benzimidazolylmethyl)amine as a ligand, and

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

• presence of transition metal salts is an essential transformation that permits the preparation N-(het)aryl-substituted amines and their derivatives including various nitrogen-containing heterocycles [1][2][3][4][5], an important class of compounds throughout chemical research. The copper-catalyzed

• , whereas originally it required very high temperatures, and some limitations including mostly low yields and intolerance of sensitive functional groups have been partially overcome [14]. A search for new efficient reagents for copper-catalyzed N-arylation has led to the recognition of arylboronic acids as

• significant role in the generation of active copper-organic intermediates from boron-organic precursors [18][19][20]. Our interest in the development of N-arylation methods resonated with recent studies focused on the addition of various C-nucleophilic reagents to 4-trifluoromethylpyrimidin-2(1H)-ones I

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• followed by the addition of CuI through an intermediate 11. This procedure provided a very low yield (7%) of a mixture of 12 (syn) and 13 (anti) products. Therefore, they opted an alternative route which involves the formation of organotin compound 14 followed by trimerization in the presence of copper

• , desulfurizion was accomplished by copper nanopowder to provide the ring-contracted desired product 155 in 30% yield along with a minor amount of 154 which was further converted into the required product under similar reaction conditions (Scheme 40). Moreover, they regioselectively converted 155 into the

• followed by quenching the hexaanionic species with selenium powder to afford 159 containing one 1,2-diselenin ring and two selenophene rings. Compound 159 was later subjected to deselenation in the presence of copper nanopowder (80–100 nm grain size) to furnish the expected compound 160 in quantitative

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• –Crafts acylation is then performed in polyphosphoric acid at 140 °C, giving anthraquinone 11 in 53% yield over two steps. Reduction of 11 to the anthracene 9 proceeded smoothly using zinc powder in 1,4-dioxane and aqueous ammonia under copper catalysis [15]. To achieve good yields, it was crucial to

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• which undergoes reduction to the dihydroxynaphthalene 8. This is then dimerized by the copper-rich enzyme to quinone arenol 9, which, following intramolecular cyclization, affords balsaminone A (4, Scheme 1). Similarly, the biosynthetic precursor of ellagic acid (5), gallic acid (10), undergoes

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• fashion similar to that of the dihydropyranone 58 [16], the 1,4-addition of dimethyl copper lithium to 65 gave the desired cis-50 as a single diastereomer [31], allowing for a convergence with the route in Scheme 7. Alternatively, the Wittig methenylation of 63, followed by a silyl ether cleavage gave 66

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• concerned the development of “classical” C–H activation reactions, while a photoredox cycle was implemented to reoxidize the metal catalyst, thus obviating the need for a stoichiometric amount of metal-based oxidants, such as silver or copper salts. In parallel, dual synergistic catalysis has emerged. In

• good yields and the authors applied the methodology for the late-stage acylation of natural ʟ-tryptophan as well as carbazole derivatives. Cu-catalyzed transformations Sporadic examples using copper as transition metal for C–H functionalization reactions in combination with photocatalysis were also

• photoinduced by visible light was promoted by copper and used the bidentate 8-aminoquinoline moiety as the DG (Figure 33) [98]. Remarkably, eosin Y, a cheap organic photocatalyst, enhanced the generation of perfluoroalkyl radicals from the corresponding alkyl iodides but a stoichiometric amount of a simple

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• cycloadditions with model alkynes. Besides two ortho- and para-bromo-substituted benzaldehydes, the azide functionalization of a fluorene-based structure will be presented. The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of the so-synthesized azide-functionalized bromocarbaldehydes with terminal

• oxazoline 24, oxazolidine 27 cyclized already during the reaction, caused by the increased basicity of the ring nitrogen. CuAAC reactions of bromocarbaldehydes We further investigated the reactivity of azide-functionalized bromocarbaldehydes 3, 4, and 5 in copper(I)-catalyzed azide–alkyne cycloaddition

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• obtained using the less reactive triphenylphosphine dicobaltpentacarbonyl complex 63 as the catalyst (Scheme 35). In a later study [72], Riera and Fustero generalized the use of trifluoromethylalkynes as substrates for the PKR. The copper-catalyzed trifluoromethylation of terminal alkynes described by Qing

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• initiates the allylic rearrangement and thereby facilitates the removal of the crucial phosphonium oxide. The outcome of this process is the structurally relevant azido moiety IIIa, which then undergoes a 1,3-dipolar cycloaddition with the copper acetylide IVa to furnish the 1,4-disubstituted 1,2,3

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• for the formation of product 15, we investigated whether the copper wire, used as a stabilizer in commercially available BTMS, could induce the observed cyclization, as was reported in the literature [37]. For that purpose, we compared the reaction run using commercially available BTMS, stabilized

• with copper wire with that using BTMS distilled prior to use but contaminated with CuBr (Table 1, entries 2 and 3). In both cases the byproducts 15–17 formed. However, when propargylamide 10 was subjected to the reaction with CuBr, in the absence of BTMS and phosphonoacetate, only starting material was