Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• . Deprotection followed by fluorination with FClO3 gave (R)- and (S)-28-3 in good yields. X-ray crystallography was used to determine the structure and confirm the absolute stereochemistry of (S)-28-3. The optically active reagents (R)- and (S)-28-3 were effective in the enantioselective fluorination of cyclic

• reported by Banks when quinuclidine was N-fluorinated with Selectfluor [62] (Scheme 67). Subsequently, in 2001, Shibata et al. presented full details of their studies including the definitive identification of N-fluorinated cinchona alkaloids by X-ray crystallography analysis and further applications [96

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• one of the products was proved by NMR analysis and X-ray crystallography. A number of different substituents was introduced to the bromotriazole scaffold, where unsubstituted and electron-rich derivatives gave a good yield, while the presence of electron-withdrawing groups decreased the product yield

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• mixture of starting material 6, the conjugate addition product 14, and a trace of the denitration product 15. The structure of both compounds was confirmed by single X-ray crystallography (Figure 4 and Figure 5). The addition of methanol is stereoselective with only a single diastereomer of 14 being

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• evaporation or diffusion. The implications for generating other co-crystals of two solids are briefly discussed. Keywords: adamantanes; crystallization; organic solids; structure elucidation; X-ray crystallography; Introduction Obtaining a crystal suitable for X-ray crystallography can be a challenge for

• X-ray crystallography were collected after more than one week. Table 1 lists the details of the structures observed. In case of the TDA/phenol co-crystals (Figure 2a/c), the asymmetric unit is made up of one host and two guest molecules, so the overall stoichiometric ratio is 1:2 (TDA/phenol). One

• most important methods for purifying organic compounds in industry [19]. It usually produces solids made up of one compound only. It is common knowledge among synthetic chemists that mixtures are difficult to crystallize. In fact, crystallization to obtain single crystals that are suitable for X-ray

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• has been a topic of strong interest over the past decades. With this in mind we have characterized a series of direct meso-halogenated porphyrins using single crystal X-ray crystallography. This is accompanied by a detailed conformational analysis of all deposited meso-halogenated porphyrins in the

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

• 9 ring system (Scheme 1). The absolute configuration of compound 9 was determined by 2D NMR spectroscopic techniques. Clear NOE signals were observed between the H-7a and Me-10 as well as the Ha-9 and Me-10 protons. Beside NOESY experiments, the structure was also elucidated by X-ray crystallography

• exclusively [41]. The configuration of oxazolidine 17 was determined by 2D NMR spectroscopic techniques. Clear NOE signals were observed between the H-7a and Me-10 as well as the Ha-9 and Me-10 protons. In addition to NOESY experiments, the structure was also elucidated by X-ray crystallography (Figure 3

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• oxide ((R)-7b) provided the product (2S,4R)-9i in a much better 8:1 anti/syn coupling diastereoselectivity (Table 2, entry 10). The configuration of the major anti-diastereomer of alkoxyamine 9j was determined by X-ray crystallography after desilylation and hydrochloride formation (see Supporting

• for 12m. However, the coupling diastereoselectivity with TEMPO (3) amounted to 4:1 for the trans diastereomers 12nA,B and exclusive for the cis isomer 12nC. The relative configuration of diastereomer 12nA was unequivocally established by X-ray crystallography of the hydrochloride adduct of the keto

• substituents. One of the minor cis diastereomers of 13j crystallized and its configuration was unequivocally established by X-ray crystallography (Figure 3, vide supra). Lactams 12l–o with cyclic subunits were also subjected to a Dess–Martin oxidation to confirm their relative configuration (Scheme 5). The

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• analysis by NMR, conformational calculation, and X-ray crystallography. A mice in vivo assay showed that (2R)-MC-27, with a six-membered oxacycle, is neuroactive, whereas the (2S)-counterpart is inactive. It was also found that TKM-38, with an eight-membered azacycle, is neuronally inactive, showing that

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• the fact that alanine mimics the secondary structure preferences of most proteinogenic amino acids, allowing the relative importance of each side chain for the biological function to be determined [23]. Classical X-ray crystallography also employs the polyalanine model for backbone chain tracing to

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• their functional architecture. Such an approach typically includes the use of a variety of high-resolution proteomic tools, cryo-electron microscopy and X-ray crystallography to achieve full molecular characterization at the atomic level. However, macromolecules such as DNA/RNA and proteins are not

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

• electrode (2 mm diameter), platinum wire counter electrode and Ag/AgCl/KCl reference electrode. X-ray crystallography The X-ray data for 6a–d and 7–9 were collected on Rigaku OD Xcalibur (6b–d, 7, 9) and Bruker D8 Quest (6a, 8) diffractometers (Mo Kα radiation, ω-scans technique, λ = 0.71073 Å) using APEX3

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• methods. These methods are summarised in Figure 1. Atomic resolution methods focus on the structure determination of protein complexes and elucidating the PPIs at a near-atomic resolution. Such methods include X-ray crystallography [12], nuclear magnetic resonance (NMR) [13], and cryogenic electron

• microscopy (cryo-EM) [14]. Traditionally, X-ray crystallography was the preferred method to solve the protein structure and determine protein–protein interfaces. However, protein crystallography has the limitation that some protein assemblies have a low diffraction quality and are difficult to crystallise

• Data Bank [16]. The main advantage that cryo-EM has compared to X-ray crystallography is that the former does not require crystals, thus making it easier or sometimes even possible at all to study flexible protein assemblies that do not crystallise. Albeit this, the main limitations of cryo-EM included

Construction of pillar[4]arene[1]quinone–1,10-dibromodecane pseudorotaxanes in solution and in the solid state

• Xinru Sheng,
• Errui Li and
• Feihe Huang

Beilstein J. Org. Chem. 2020, 16, 2954–2959, doi:10.3762/bjoc.16.245

• reports [44][45]. We found that H and G can be used to build a [3]pseudorotaxane in the solid state but a [2]pseudorotaxane in solution. Results and Discussion Host–guest complexation in the solid state Cocrystals of H and G were obtained by slow evaporation of the solution in methanol. The X-ray

• crystallography revealed that two host molecules complex one guest molecule, forming a [3]pseudorotaxane in the solid state (Figure 1). In the crystal structure, the alkyl chain of the guest is threaded through the cavities of two host molecules, which is stabilized by multiple CH∙∙∙π interactions and hydrogen

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• complexity of glycans in glycoproteins have been, and currently remain, significant challenges in structural biology. These aspects present unique problems to the two most prolific techniques: X-ray crystallography and cryo-electron microscopy. At the same time, advances in mass spectrometry have made it

• the validation of 3D glycoprotein structures. Keywords: electron cryomicroscopy; glycoinformatics; glycomics; Privateer; X-ray crystallography; Introduction Glycosylation-related processes are prevalent in life. The attachment of carbohydrates to macromolecules extends the capabilities of cells to

• glycoproteins Several experimental techniques can be used to obtain 3D structures of glycoproteins: X-ray crystallography (MX, which stands for macromolecular crystallography), nuclear magnetic resonance spectroscopy (NMR) and electron cryomicroscopy (cryo-EM). As of publication date, the overwhelming majority

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

• negatively charged patches, depending on the functional groups present. X-ray crystallography is a useful tool to obtain structural information about the binding modes of supramolecular ligands on proteins (reviewed in [76]). However, the crystallization of proteins with supramolecular ligands can be very

• phosphonato-calix[n]arenes of different ring sizes (n = 4, 6 or 8) to Cyt c [20][23][24][26][27][28] and the antifungal protein PAF [25] as model proteins. These studies combined 15N-HSQC titrations with X-ray crystallography, isothermal titration calorimetry (ITC) and size exclusion with light scattering

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

• two days to afford the required complex whose structure was confirmed by X-ray crystallography (Scheme 37). 3 Synthesis of heterosumanene derivatives Doping the backbone of buckybowls such as sumanene and corannulene with heteroatoms (N, P, O, S, Si, and Te) is a promising tactic to modulate the

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• in 3d proceeded smoothly with acetyl chloride in the presence of sodium hydride to afford 5 in good yield. The structure of the product and the site of acetylation was confirmed by X-ray crystallography of a single crystal of 5 [71] (Figure 3). The methylated and benzylated derivatives 6 and 7 were

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• afforded trace amounts of 3a and 4a, both of which were obtained as a mixture of diastereomeric isomers (Table 1, entry 1). The stereochemistry of the major product 4a was determined to be trans,trans (all-equatorial) by X-ray crystallography (Figure 1). Among the solvents tested, less polar solvents, such

• afford nitrophenol 5b, which eluted with hexane/ethyl acetate 8:2 (41.7 mg, 0.17 mmol, 34%) as yellow solid. When the other nitroalkenes 1c–f were used, the reaction was conducted in the same way. X-ray crystallography of the major isomer of 4a. The thermal ellipsoids indicate 50% probability. Resonance

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• developed by reacting 5-amino-1,2,3,4-tetrazole with aromatic aldehydes and cyanamide in pyridine under controlled microwave heating with high yields. X-ray crystallography confirmed the structure of the obtained products. Keywords: microwave irradiation; N2-(tetrazol-5-yl)-6-aryl/heteroaryl-1,3,5-triazine

• -2,4-diamines; one-pot synthesis; X-ray crystallography; Introduction The family of triazines is of considerable interest in fields related to organic and medicinal chemistry. 2,4-Diaminotriazines are privileged scaffolds exhibiting diverse biological activities such as antibacterial [1], anti-HSV-1

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• product 3a was unambiguously confirmed using X-ray crystallography [57]. To further extend the diversity of the reactivity of the imines in this process, we also attempted the use of a reducing agent in the reaction of 1a. Pleasingly, the reaction of 1a with 2 equivalents of the Hantzsch ester in CH3CN

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• emitting diodes (LEDs) were purchased from Topbright. X-ray crystallography Single crystals of 2c and 4a of suitable quality for X-ray diffraction measurements were grown by slow diffusion of n-pentane into CH2Cl2 solutions of the crude product at –18 °C for several weeks. One selected single crystal was

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• Chaudhuri on GAO mimics [11][12][13], Safaei and Storr have reported Cu(II) complexes bearing a non-innocent amidophenolate type benzoxazole ligand which was fully characterized by X-ray crystallography and other spectroscopic techniques (Scheme 1) [14]. These complexes were found to perform the aerobic

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• twofold [3 + 2] cyclopentannulation and subsequent twofold [4 + 2] benzannulation. The structure of 1 is unambiguously confirmed by X-ray crystallography; 1 adopted a twisted geometry due to the steric hindrance of the phenyl rings and the hydrogen substituents at the bay regions. Notably, compound 1

• 1 were obtained by slow evaporation from a carbon disulfide solution, allowing us to disclose the molecular structure by X-ray crystallography (Figure 2a). As shown in Figure 2a, the crystal structure of 1 clearly displayed a nonplanar conformation, resulting from steric repulsion between the phenyl

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• combination of 20 mol % of tetrabutylammonium bromide (TBAB) and NaOH (20 mol %) yielded the desired product, 2,2,2-trifluoro-1-(1H-indol-3-yl)ethan-1-ol (3a) in 93% yield (Table 1, entry 4). The product 3a was isolated by filtration and confirmed by NMR and X-ray crystallography analysis (CCDC-1973322, see

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• reaction between 1a with 2a proceeded to give phenoxasilin 3a in 60% yield (Table 1, entry 1). The structure of phenoxasilin 3a was confirmed using single-crystal X-ray crystallography (see Supporting Information File 1 for details) [42]. Upon increasing the reaction temperature to 140 °C, the yield of 3a