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

• treated with (−)-menthoxyacetyl chloride, followed by separation of the diastereomers. The chiral auxiliary was then removed with LiOH and the resulting sultams 27-5 as single enantiomers were fluorinated with 15% F2/He in the presence of KF to produce optically pure N-fluorosultam reagents (R)- and (S

• of 28-2, which was accompanied by 45% of unreacted 28-1. Interestingly, pure (R)-isomer 28-1 was obtained in 20% yield from the unreacted 28-1. The diastereomer separation of 28-2 was achieved by column chromatography to separate the (R)- and (S)-isomers of 28-2 in 21 and 31% yields, respectively

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• mixture was incubated for 1 h at 60 °C. For separation of polysaccharides, 180 µL 5 M NaCl and 80 µL 10% CTAB were added and the mixture incubated further for 10 min at 65 °C. To extract nucleic acids by phase separation, 860 µL chloroform/isoamyl alcohol (24:1) was added and incubated on ice for 30 min

• detector (interface temp, 270 °C; quadrupole temp, 150 °C; source temp, 230 °C; electron energy, 70 eV). Chromatographic separation was achieved with an initial oven temperature of 45 °C held for 2 min, which was then increased to 180 °C with a gradient of 6 °C min−1, and then further increased to 300 °C

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

• determined by 1H NMR spectroscopy. Chromatographic separation was carried out on silica gel 60H (200–300 mesh) manufactured by Qingdao Haiyang Chemical Group Co. (China). High-resolution mass spectrometry (HRMS) was measured on a Thermo-DFS mass spectrometer. NMR spectra were recorded on a JEOL 600 NMR

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• % and exclusively β-selective [11]. Isomeric separation of this complex mixture was not completed at this stage and the material was next deprotected using hydrogenolysis to remove the benzyl groups. This furnished 20 in excellent yield (96%) as a 3:1 α/β mixture (δ 100.5 ppm [1JC1-H1 = 172 Hz, for the

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• or minimize the formation of diol 11 by performing the reduction step at temperatures lower than 15 °C but this significantly reduced the yield of the desired product, even with longer reaction times. Therefore, we had to be satisfied with separation of desired product 8 from unwanted 9 after the

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• strands of the duplex with separation of one regular base pair from each other [54]. 1,5-Furanosyl double-headed nucleosides In this category, the nucleosides contain the first natural nucleobase at the C-1′ position and the second natural nucleobase/aromatic moiety/heterocyclic ring attached at the C-5

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• scale-up equating to prolonged run times. As a result, alternative support formats have been investigated. In this context there has been a growing interest in the use of functionalised hollow fibres including their application as membranes for gas separation [110] (e.g., CO2 absorption [111]) as they

• mixture is biphasic, and a preliminary separation is carried out before entering the reactor coil. After discontinuous purification procedures, the product 82 was yielded in 98% purity (72% yield). The second step, instead, is an acid-catalysed cyclisation which employs the same tubular reactor at lower

• system with the steam being recycled back through the reactor. After phase separation, the obtained mixture was enriched to 85% of 83 (equating to a 73% isolated yield). Once the reaction conditions were optimised, the apparatus can merge with other flow systems to develop a parallel continuous multistep

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• , thus leading to an enhanced optical absorption, improved electron-hole separation and easy dispersion in polar solvents [32]. CN-K, which can be easily prepared by the direct KCl-induced structure remodeling of bulk g-C3N4 [33][34][35][36], showed great potentials for future industrial applications

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

• , the same porphyrin overlap seen in Figure 2A is apparent (Figure 11A) with a separation of 3.359(2) Å between the porphyrin layers. This is coupled with a short contact between the bromine atoms and the meta-hydrogen of the phenyl ring tethering porphyrin molecules to the one above it (Figure 11B

• above with a separation of 3.255(5) Å (Supporting Information File 1, Figure S18). Interestingly, this structure features both arrangements previously seen with a close packing observed between both pyrrole (Supporting Information File 1, Figure S19A) and hexyl (Supporting Information File 1, Figure

• Information File 1, Figure S30) establish the packing pattern seen in Supporting Information File 1, Figure S23. As with compound 1, the stacking between the porphyrin layers is organized with the bromine atoms overlapping with each other at a separation of 3.306(3) Å among the porphyrin macrocycles. In

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• and 12 under these conditions produced the expected thioglycosides 18 and 19, respectively. Difluorinated derivative 13 decomposed on reaction with the PhSTMS/ZnI2 system. The separation of the anomers of products 14–19 was attempted because of the risk of thiophenyl migration in the subsequent C6

• deoxyfluorination, which would likely occur with the β-anomers of 14–19 [41]. The complete separation of the α-anomer by conventional silica gel column chromatography was possible for thioglycosides 14, 16, 17, and 19, while the products 15 and 18 were obtainable as enriched α-anomers (α/β ≥ 3.3:1). Cleavage of the

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• reaction was cooled to room temperature, and the product was isolated, either by adding 4 mL of water, which dissolves the DES, and extracting the nitroalkane with AcOEt, or by direct separation of the organic residue from the eutectic mixture (see below for recycling experiments and Supporting Information

• extraction of the product and its separation from the eutectic mixture. However, when the recycling protocol was studied, in order to reuse the DES, at the end of the reaction, water was not added, and the product was extracted by simply adding ethyl acetate and separating the upper, organic phase. The DES

• the use of any organic solvent, the reduction of 3h was performed with a 1 M substrate concentration and afforded, in DES B, nitroalkane 4h in 74% yield, which was isolated as pure compound by a simple liquid–liquid biphase separation from the eutectic mixture (see details and pictures in Supporting

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• using a Histopaque®-1077 (Millipore Sigma, MA) density separation to collect the buffy coat. Thereafter, the buffy coat was subject to a Percoll® (Cytiva, MA) density separation to enrich for the monocyte population in the buffy coat. Monocytes were counted and stored in Cyrostor-C5 (BioLife Solutions

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

• undesired isomer were produced, recovery of unreacted 6 was simple and the quantity of 8 (<5%) was reduced compared to all previous attempts. Chromatographic separation permitted the removal of 8 and the isolation of a pure sample of compound 4. Synthesis of compound 1 Having produced the key intermediate 4

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• scaling up the preparation of two pincer-type thioamides, we have successfully developed a convenient process with ethylene glycol to replace ethanol during the workup, including a traditional phase separation, extraction, and recrystallization. The newly developed chromatography-free procedure did not

• separation by careful column chromatography is necessary because of both the similar polarity and the stoichiometric amount of the formed compound A. With regard to this, the use of LR was always limited to small-scale preparations [6][8]. Other than the exploration of potential surrogates of LR for the

• , we herein reported an efficient work-up procedure of applying LR by utilizing ethylene glycol to decompose the compound A (Figure 2). With a combination of some usual operations, such as, phase separation, extraction and crystallization, the desired thioamide products were efficiently obtained in

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• creates a chiral center at the phosphorus atom resulting in a mixture of 2n diastereomers, where n is the number of modified phosphate groups. The reverse-phase (RP) HPLC purification occasionally results in the separation of individual diastereomers (usually for ONs with a single modification), which

• , the separation of ONs with varying numbers of modifications was not ideal as there were only marginal changes in the retention time in RP-HPLC. Therefore, ion-exchange (IE) HPLC was used for purifying these ONs. The substitution of each phosphate with N+ modification, resulted in a shorter retention

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• CH2Cl2. The low yield of this reaction was due to the formation of two isomeric products as revealed by TLC and subsequent analysis by analytical LC–MS. The NMR spectra of both isomers, after chromatographic separation, showed different chemical shifts for the protons at C2 position of the DBO ring

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

• plastics. Heterogeneous systems are preferred by industry due to the easier separation from the reaction mixture, reuse and integration into existing reactor equipment [106][107]. Metal-based catalysts have been used for both solvolytic and hydrogenolytic methods, wherein the latter are usually achieved by

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• . Isolation of 9-hydroxysteroids A frozen culture supernatant was melted at room temperature or in a warm water bath, then poured into the separation funnel, saturated by the addition of solid sodium chloride and extracted with EtOAc. The extract was concentrated in vacuo to give a solid residue that was

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

• be effective here (Scheme 2). Thus, the esterification mediated by 2-methyl-6-nitrobenzoic anhydride (MNBA, Shiina esterification) [9], followed by chromatographic separation of the diastereomers, successfully generated the (2S)-isomer 9* (tR 7.0 min) and the (2R)-isomer 9 (tR 11.5 min) in 45.3% and

• 44.4% yield, respectively (Figure 2). It should be noted here that DCC and DMAP drove the esterification in a poor yield (51% in total for 9 and 9*). As shown in Figure 2, the preparative separation was performed cleanly even on a gram-scale synthesis (1.70 g). The structures, illustrated in Scheme 2

• separation of 20* and 20 was realized by preparative HPLC with a CHIRALPAK IC column to furnish 20* (tR 9.6 min) and 20 (tR 11.8 min) in a 20*/20 ratio of 53:46, for which the stereochemical configuration was computationally and spectroscopically determined as 2S and 2R, respectively, one step later for 21

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• synthesis starting from the other thiobenzamides 4b and 4c and 3-bromooxindoles 1b and 1c (Table 4). From the inspection of Table 4 it is obvious that the isolated yields are lower (19–60%) but this is mainly due to the requirement for a more complex separation involving repeated column chromatography and

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• unexpectedly high selectivities, ranging from 87:13 to 98:2 (Scheme 3). The isolated product yields were moderate to good and the products were generally obtained as mixtures of regioisomers. Column chromatography allowed the separation of pure isomers of 2a, 2a’, 3a, 3b, 3d, 3h, 3l, 3m, and 3n. However, no

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

• success of our DMF-free systems lies in the generation of sterically demanding cationic species, [P4-t-Bu]H+ or glyme capsulized K+, resulting in the stabilization of CF3− from HCF3 by ion separation. The sterically demanding [P4-t-Bu]H+ or encapsulation of K+ by glymes effectively inhibits the contact of

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• between the sulfur and an ester oxygen. This phenomenon was first described in supramolecular structures by Gleiter [59] and later also used to explain the outcome of organocatalytic reactions [60]. The pure stereoisomers of 42 were isolated by preparative HPLC, for which the best separation was achieved

• -(methylsulfanyl)acrylate (42). Volatiles from Celeribacter spp. Supporting Information Supporting Information File 36: DMSP demethylation pathway in Celeribacter spp. and copies of spectra. Acknowledgements We thank Andreas Schneider (Bonn) for HPLC separation of (E)- and (Z)-42. Funding This work was funded by

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• structure in Figure 4c). For more details, see Supporting Information File 1. Charge transfer (CT) during excitation plays a key role in many technological applications because CT states correspond to a light-activated electron–hole separation where the positive and negative charges are distant enough to

• water vs 0.017 Å in n-hexane). Note, that a greater positive τ index indicates a stronger charge separation as a result of the electron transition [36]. Hence, in the case of n-hexane, the distribution of the positive and negative charge is almost not separated, and the CT is small. However, for the