Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• ]. Specifically, they have dealt with the addition of potassium aryltrifluoroborates to conjugated cyclic enones differing in ring size [32]. The catalysts PdL1a,b exhibited great conversion and enantioselectivities (up to 99% and up to 96% ee) for various combinations of nucleophiles and enones (Table 1). The

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

• such as lead tetraacetate, potassium permanganate, or refluxing hydrogen peroxide were shown to produce urea-derived degradation products [3]. Biguanides also possess a remarkable capability to form stable metal complexes, a property that was already noticed by B. Rathke in 1879 [4]. Indeed, he relied

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• aminohydroxylation process starting from allylic carbamates usually carried out in the presence of potassium osmate [24][25][26][27][28]. In recent years, we have extensively studied the stereoselective synthesis, as well as catalytic and pharmacological applications of monoterpene-based 3-amino-1,2-diols, which are

• synthesize novel, cyclic potentially analogues of sphingosine, incorporating a lipophilic natural pinane skeleton, starting from commercially available monoterpene-based allylic alcohols via a stereoselective hydroxyamination in the presence of a potassium osmate(VI) catalyst. We also planned to explore the

• carbamate 8 in good yield [27][28][36]. In the next step, the aminohydroxylation was accomplished by potassium osmate(VI) as the catalyst and t-BuOCl in the presence of DIPEA affording oxazolidine-2-one 9 [27]. The reaction was found to be highly stereoselective, giving exclusively the diexo-fused tricyclic

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• nucleophiles. The second report, by Scheeren [7], working from a bis(phenoxy)chloromethane synthesis reported by Scheibler [8], described the conversion of phenyl orthoformate to bis(phenoxy)chloromethane with acetyl chloride and anhydrous hydrogen chloride, followed by reaction with potassium

• strategy, we were delighted to observe that the desired compound, 4, was produced as the major product, in 39% yield (72% yield based on recovered starting material) when 6 was reacted with dibromofluoromethane in the presence of excess potassium phosphate in acetonitrile (Scheme 4). Smaller amounts of the

• possible with potassium hydroxide as a base, while potassium carbonate gave only traces of the desired product. DMF was found to be an inferior solvent. All these changes led to larger quantities of the undesired isomer 7, with respect to 4. Attempting to push this reaction to higher conversion of 6 with

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• [32] found a bifunctional group reaction of perfluoroalkylation and β-alkenylation by a perfluoroalkyl radical. Perfluoroalkylation product 93 was synthesized by utilizing (E)-3-methyl-1-phenylhept-1,6-dien-3-ol (92) and perfluorobutyl iodide (28) as substrates and potassium phosphate and DABCO as

• visible-light-mediated synthesis approach of arylphosphonates initiated by an EDA complex. Diethyl phenylphosphonate (165) was given by exploiting diphenyliodonium trifluoromethanesulfonate (163) as electron acceptor, triethylphosphite (164) as electron donor, potassium carbonate as base, and CH3CN as

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• first gave ester 181 and then acid 182 (Scheme 31), the sodium and potassium salts of which are well soluble in water. The compound has antiviral and anticancer activity as well as pronounced antioxidant properties combined with low toxicity. Diarylmethanofullerene 183 was synthesized according to

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• described in detail. Solvolytic depolymerisations can also be promoted by metal-free soluble acid or base catalysts. However, concentrated solutions, quasistoichiometric amounts or strong mineral acids (HNO3, H2SO4, H3PO4) or bases (NaOH, KOH, potassium butoxide) are often required, particularly for

• and a 20:1 excess of strong base potassium tert-butoxide as cocatalyst (Table 1, entry 1) [183]. Although the reaction mechanism was not investigated in detail, it was suggested that cleavage of the ester linkage may occur in a concerted manner through the reported heterolytic route [184][185]. The

• chloride catalyst precursor with potassium butoxide in a 2:1 molar ratio, resulted in a nearly quantitative yield of BDM and EG at a slightly higher reaction temperature (160 °C, 54 bar H2, Table 1, entry 2). Interestingly, PET flakes from postconsumer bottles could be used, showing the catalytic system to

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

• reported by us [30]. It is known that the alkylation of phthalazinones depends on the reaction conditions and can proceed in two ways involving either the nitrogen or the oxygen atom (lactam–lactim tautomerism). It has been proven that potassium salts of phthalazinones or the bromo derivatives are

• In conclusion, we have demonstrated an efficient synthesis of 2-substituted (alkyl, aminoalkyl) 4-aminophthalazinones 5 and 6 via the direct bromination of phthalazin-1(2H)-one (1) with potassium tribromide, followed by the alkylation of 4-bromophthalazinone 2 with methyl iodide, isopropyl iodide or

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• nucleophilic esterification of potassium 1-(N-benzyloxycarbonylamino)alkylphosphonates 172 with alkyl halides in the presence of 18-crown-6. They also prepared a phosphonodepsidipeptide 174 with ethyl chloroacetate (173) as an electrophile (Scheme 33) [53]. The macrocyclic peptidyl phosphonodepsipeptide 180

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• group reported novel DMF-free systems for the nucleophilic trifluoromethylation reaction using HCF3, including the phosphazene base P4-t-Bu (P4-t-Bu), in 2013 (Scheme 1c) [45] and a potassium tert-butoxide (t-BuOK) or potassium hexamethyldisilazide (KHMDS)/glyme combination in 2018 (Scheme 1d) [46]. The

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• DMF (8 mL) were added potassium carbonate (1.06 g, 7.67 mmol, 1.2 equiv) and homoallylic bromide (670 µL, 6.51 mmol, 1 equiv) at 40 °C. After overnight stirring at 40 °C, the reaction mixture was concentrated under reduced pressure. The residue was redissolved in ethyl acetate, washed with a saturated

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• yield EPR signals of the same multiplicity as they were observed in the case of spectra of monoreduced species of 6d, but the value of hyperfine splitting constant on protons of the methyl groups of the acetylacetonate fragment (0.17 G for potassium semiquinonate, see Table S4 in Supporting Information

• File 1) is less than that in 6d (0.31 G for potassium semiquinonate). This could be explained by the fact that unlike 6d, the acetylacetonate fragment in 7 lies in an almost orthogonal plane relative to the semiquinone ring that disfavors delocalization of the spin density on the methyl groups. The EPR

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

• were increased when potassium fluoride and 18-crown-6 were added to the reaction mixture [20]. Dehydrohalogenation of dichlorodifluoromethane under phase-transfer catalysis: Difluorocarbene can be generated from chlorodifluoromethane by phase-transfer catalysis (PTC) through the reaction with NaOH or

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• ether was the reaction of phenol with 2-chloro-1,1,1-trifluoroethane, also known as HCFC-133a, in the presence of potassium hydroxide (KOH) to give the gem-difluoromethyl ethers along with the formation of 1-fluoro-2-chlorovinyl ether (route (d), Scheme 1) [41]. On the basis of our previous reports, we

• did not occur at all when potassium carbonate was used as a base, because the deprotonation of phenol became slow due to the low basicity (Table 1, entry 9). With the optimal reaction conditions (Table 1, entry 8) in hand, we next examined the scope of the reaction (Table 2). When an electron-rich

• the product 2a in 27% yield and 1a was recovered in 54% (Scheme 4a). Based on these results, we speculated that the initially generated phenoxide 4 or potassium hydroxide remaining in the reaction mixture could deprotonate halothane to provide the fully halogenated ethylene 5 (Scheme 4b) [32][33][45

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

• a 6-step sequence from 3,4-dihydro-2-ethoxy-2H-pyran (58) [50]. Treatment of 58 with a mixture of butyllithium and potassium tert-butoxide in the presence of TMEDA and pentane, followed by reaction with the corresponding alkyl iodides in THF, and finally, acidic cleavage of the generated acetal

• tetroxide and potassium periodate, to provide (−)-adaline (1) and (−)-euphococcinine (2). Originally, Yu et al. synthesized (−)-adaline (1) with good yields and high enantiomeric excess using catalytic asymmetric allylation from commercially available 58. Additionally, intramolecular allylic transfer led to

• stereospecific semipinacol rearrangement in 78% yield over two steps. The resulting terminal alkene (−)-70 was submitted to Vacker's conditions to produce methyl ketone (−)-71 in 93% yield. The treatment of this ketone with potassium trimethylsilanolate induced a 1,5-Michael type reaction, via attack of tethered

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• (3.01 g, 10 mmol) in DMF (16 mL) was added potassium phthalimide (1.85 g, 10 mmol) in portions. The mixture was stirred at room temperature for 5 h. Then, water (30 mL) was added, and the formed precipitate was collected by filtration and washed with water. Recrystallization from ethanol afforded

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

• such as potassium tert-butoxide or sodium hydride resulted in no formation of the desired product 3a because 2a was decomposed under the harsh reaction conditions (Table 1, entries 2 and 3). Thus we opted to employ another substrate 2b bearing a phenylthio group which polarizes the α-C–H bond to lead

• 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

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

• with a complementary base sequence [10], the AuNPs with peripheral carboxylate groups introduced by the Hupp group [11] that responded to divalent transition metal ions, or Chen at al.’s crown ether-decorated AuNPs that allowed the sensing of potassium ions [12]. Numerous other such probes have been

• nanoparticle surface after immobilization. Compound 2 was prepared by starting from potassium phthalimide and 1,12-dibromododecane (Scheme 2). The product resulting from this step was treated with bis(2-pyridylmethyl)amine to give a DPA derivative that was coupled to (R)-lipoic acid after deprotection to

• . Conditions: i) potassium phthalimide, DMF, 25 °C, 18 h, 67%; ii) 2,2'-dipicolylamine, K2CO3, KI, acetone, reflux 14 h, 50%; iii) N2H4⋅H2O, ethanol, 25 °C, 16 h, 56%; iv) (R)-lipoic acid, EDC⋅HCl, DMAP, CH2Cl2, 25 °C, 18 h, 52%. Minimum salt concentrations required to precipitate and to subsequently

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

• %) and potassium hydroxide (90%) were purchased from Sigma-Aldrich. All chemicals were used without further purification. Preparation of β-CD samples Analogously as described in [14]. General procedure for the synthesis of mono-6-O-(2-mesitylenesulfonyl)-β-cyclodextrin β-CD (1500 mg, 1.32 mmol) and MtsCl

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• interactions are marked with two-headed arrows. Mechanism of the halofluorination reactions of the substrate 19. X = Br (compounds a), I (compounds b), Cl (compounds c). Synthesis and halofluorination of the imide 24. Cyclizations of halofluorinated diesters with potassium tert-butoxide. Relevant NOESY

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

• Discussion Synthesis of the host TBTQ-(OG)6. The sugar-functionalized host TBTQ-(OG)6 was synthesized starting from the known compound TBTQ-(OH)6 (Scheme 1) [31][32][33]. The reaction of TBTQ-(OH)6 with propargyl bromide in the presence of potassium carbonate gave the hexakis-propargyl ether, TBTQ-(OP)6, in

• imaging. Freeze drying was conducted on a Scientz-18N freeze dryer (Scientz Biotech, Zhejiang, China). Synthesis of TBTQ-(OP)6. A mixture of TBTQ-(OH)6 (2.17 g, 5.56 mmol), potassium carbonate (9.23 g, 66.8 mmol), and propargyl bromide (5.40 g, 44.5 mmol, 98 wt %) in acetonitrile (100 mL) was stirred and

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• been used to design custom plugs for the negatively charged central cavity of tetrameric proteins, exploiting the four-fold symmetry of the ligand [39][40]. In the case of tetrameric voltage-dependent potassium channels, binding of the calixarene to the central pore of the channel results in reversible

• inhibition of potassium ion transport [39]. Another guanidinium-calixarene variant was designed to hold together the four tetramer subunits of a p53-R337H tumor suppressor mutant and thus restore tetramer stability [40]. Further examples for ligands targeting negatively charged patches on proteins include

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

• synthesis. Experimental General procedure of trifluoromethylation: Aryl iodide 1 (0.1 mmol), 2 (56 mg, 0.2 mmol), CuI (3.8 mg, 0.02 mmol), 2,2’-bipyridyl (12.5 mg, 0.08 mmol), and potassium carbonate (55.6 mg, 0.4 mmol) were mixed in benzonitrile (1.0 mL), and the mixture heated to 90 °C. After 48 h

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

• bromide in 1-bromo-4-chlorobutane (16) with sodium azide to give azide 17 in 52% yield (Scheme 5). Treatment of 17 with potassium phthalimide and catalytic potassium iodide was followed by hydrazine unmasking to give the desired aminoazide 18 in 37% over the two steps. Reductive amination of 18 with dial

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• recorded on an Inova 400 instrument. Fourier transform infra red absorption spectroscopy (FTIR) was carried out with a Shimadzu IRAffinity-1S spectrometer. Potassium bromide (KBr) pellets were prepared using 100 mg of potassium bromide and 1.0 mg of sample. The spectra were recorded under inert atmosphere

• and a pure potassium bromide pellet was used as background. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to determine the boron (B) concentrations and was performed in triplicate using a Varian 720-ES Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES). An