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

• decomposition process that is observed with N-F reagents that have an α-proton and occurs under strong base conditions. 1-11. Perfluoro[N-fluoro-N-(4-pyridyl)methanesulfonamide] In 1990, Banks and co-worker reported perfluoro[N-fluoro-N-(4-pyridyl)methanesulfonamide] (11-2) [54]. Starting from

• crystalline solid with a high decomposition point of ca. 170 °C. The bisOTf salt 22-1a, bisBF4 22-1d, bisSbF6 22-1e, and bisPF6 22-1f are easy-to-handle because they are non-hygroscopic and stable crystals. As shown in Figure 6, 22-1a,d,e mediated a quantitative conversion of anisole to isomers of

• carbanions [90]. The precursor 27-1, which was prepared in a three step protocol from saccharin, was fluorinated with FClO3 to give 27-2 in good yield (Scheme 60). Direct fluorination of 27-1 with 10% F2/N2 had failed because of decomposition. Various ketone enolates were successfully fluorinated with

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• formation of the corresponding phosphine oxide derivative as the only decomposition product was observed. The results, shown in Figure 3, reveal that the oxidation stability is decreasing in the order TPP > MMTPP > TMTPP, which is in line with electrochemical studies showing a decrease of the oxidation

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

• suggesting rearrangement does not occur. Reaction of the electron-rich 4-hydroxy[2.2]paracyclophane led to decomposition while the electron-poor derivatives barely reacted. Treatment of [2.2]paracyclophane (1) with various acids (nitric, sulfuric, perchloric, and acetic acid) led to differing results

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• decomposition of N-pyridylbenzotriazoles. Later, the reaction conditions were modified to make this reaction more versatile and operationally simple such as by the use of microwave irradiation [12]. Meanwhile, the Fischer indole synthesis was successfully extended for the synthesis of significant biologically

• -indole-2-carbaldehyde (1h), impeded the conversion to γ-carboline 3ha (structure not shown) due to probable decomposition and decrease in nucleophilicity at the 3-position in substrate 1h. Plausible mechanism for the formation of γ-carbolines The probable mechanistic explanation (Scheme 3) 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

• tosylate under basic conditions affording 24 in a yield of 83%. The displacement of the tosyl group with an azide whilst heating the reaction at 80 °C allowed for the isolation of azide 25 in a good yield of 75%. Heating at higher temperatures resulted in product decomposition. Hydrogenation of the azide

• neutralize the TFA salt to obtain the free amine were unsuccessful, most often resulting in product decomposition. Also the attempted product purification by recrystallization from methanol did not improve the purity of the product. Spectroscopic data of the synthesized ent-pavettamine and the pavettamine

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

• and can interfere with the color reaction and tests used to detect plant poisons in forensic investigations. There is currently a resurrection of interest in nitrogenous small molecules associated with corpse decomposition since the profile of these compounds can be useful to assess postmortem

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• decomposition starting from 307 °C and ending up with 8.44% total weight at 800 °C, at first place. HGCM-PAA maintained thermal stability up to 305 °C with 8.4% mass change and resulted in 12.6% total weight whereas HGCM-PAAM was stable up to 250 °C with 7% mass change ending up with 13.4% total weight. At last

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

• auxiliary yielded superior results in flow [89]. Alkylation of oxazolidinone 19 with benzyl bromide (20) in batch gave only a combined 31% yield of the benzylated products 21, with a 70% diastereomeric excess (de), accompanied by 10% decomposition to the N-benzyl derivative 22. In flow, however

• , decomposition was completely avoided and an improved yield of 41% was achieved with an associated increased of the de to 82%. Whilst the observation of improved processing control under flow conditions compared to batch is not necessarily always the case, there are many instances in which other advantages can

• different approach was taken in that the two starting materials were combined into a single stream and the base (potassium tert-amyloxide) added via a separate channel. This was presumably established to avoid base-mediated decomposition of the starting material 44 if prepared as a stock solution. The

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

• CSD. In this study we have used the Hirshfeld fingerprint plots together with normal-coordinate structural decomposition and determined crystal structures to elucidate the conformation, present intermolecular interactions, and compare respective contacts within the crystalline architectures

• , does not change the core size to any large degree. To further investigate these subtle differences, we can look at their normal-coordinate structural decomposition (NSD) profiles (Figure 7) [28]. It can be observed that in the out-of-plane (OOP) distortion modes, the overall DOOP is almost tripled

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

• . Deoxyfluorination at C6 should then afford intermediates 6. Protecting-group manipulation of intermediates 4 and 6 should deliver the required fluoro analogs. The initially contemplated conversion of intermediates 3 into acetates 5 [26], followed by base-catalyzed O-deacetylation, led to substantial decomposition

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

• decomposition over time. Only low to average conversions (up to 81%) and only average enantioselectivities (up to 80% ee; Table 37) were achieved for the studied substrates [62]. One of the most recent contributions to this topic came from the group of Hong and Stoltz in 2020. Here, attention was focused on the

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• ). Further attempts to optimize the reaction conditions showed that the reaction mostly led to decomposition of the starting material in polar protic solvents or in the presence of bases or additives other than triethylamine (cf. Supporting Information File 1). However, the product was isolated in a moderate

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• inhibited the desired phosphinylphosphination (see, alkyne 2f), probably because of the decomposition of Ph2P(O)PPh2. Furthermore, an electron-deficient alkyne such as methyl propiolate (2h) failed to provide the desired adduct (3h) [61]. 3-Phenyl-1-propyne (2i) and cyclohexylacetylene (2j) gave 3i and 3j

• mind, a plausible reaction pathway is shown in Scheme 5. Decomposition of the radical initiator (V-40) generates In•, which attacks selectively at the trivalent phosphorus atom of Ph2P(O)PPh2 to form Ph2P(O)•. Then, Ph2P(O)• adds to the terminal carbon of an alkyne to afford the carbon-centered radical

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

• reaction increased with time up to 5 min a further increase in time decreased the yield, attributed to the formation of byproduct and decomposition of product. A plausible mechanism proposed by the authors indicates the Knoevenagel condensation between 5 and 93 to form adduct A and undergo an aza-ene

• functionalized dihydro-1H-pyrazolo[3,4-b]pyridines 99 under the same conditions. Moreover, the reaction preceded well even with other 1,3-diketones along with primary heterocyclic amines (Scheme 36). The modest yields of 99 compared to 97 were reasoned with the decomposition of the amines. Suprisingly, the

• adaptation of conventional strategy delivered the aromatized product in better yields (62–75%). The increased yield was attributed to the lower decomposition observed for the starting material amines. The authors proposed that the final aromatized product was derived from the initial formation of the dihydro

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

• effective in the decomposition of the inherent stoichiometric six-membered-ring byproduct from the Lawesson’s reagent to a highly polarized diethyl thiophosphonate. The treatment significantly simplified the following chromatography purification of the desired thioamide in a small scale preparation. As

• following the same procedure as described above for the EtOH treatment. To our surprise, the decomposition was much slower as expected (TLC monitoring, see Supporting Information File 1). It was assumed that the ring-opening could be influenced by water or by the in situ-generated thiophosphonic acid. Thus

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• significant thermal decomposition of the substrate and/or the product (Table 1, entries 15–17). The varying acetonitrile/water ratio demonstrated no impact on the product yield (Table 1, entries 18 and 19). The reaction was found to proceed well in pure acetonitrile as well (Table 1, entries 20–22) and even

[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

• can be due to a number of reasons. First, two cyclopropanation mechanisms are equally likely in the thermal reaction of diazo compounds with C60 fullerene: a) preliminary carbene formation due to the thermal decomposition of diazo compounds, followed by synchronous addition to the double [6,6]-bond in

• the synthesis of fulleropyrazolines is available, their decomposition has been studied insufficiently. The factors determining the relative stability of monoadducts obtained in reactions of C60 with diazo compounds also remain an open issue. Some of the studies by Wudl and co-workers [108] deal with

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

• usually synthetic polymers recalcitrant to decomposition, and hence liable to accumulate in landfills or the environment when discarded [5][6]. Not all plastics can be reused, and thus having limited economic value [7][8]. Plastics may release toxic compounds dangerous to human health and the habitat [9

• decomposition of the polymeric chain, monomers or oligomers, depending on the waste polymer and the process. The as-obtained compounds can be reused as raw materials for the process industry (hence the term feedstock) to produce chemicals, fuels or other polymers. Thermochemical processes include pyrolysis [55

• ]. However, solvolytic methods are usually not cost-competitive and energy-intensive [86], while they may involve the management of large amounts of noxious solvents and a variety of (decomposition) byproducts [87][88]. Depolymerisation products of course depend on the polymer, the solvent and the reaction

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

• (m/z = 422.3 and 424.3 Da) showed at the first step the loss of an aminoalkyl fragment (C2H3NMe2 = 71.1 Da) to form the ions 9 ⇌ 10 (m/z = 351.2 and 353.2 Da). Because of the lactam–lactim tautomerism the further complex decomposition can proceed through two fragmentation routes: 1) with the loss of

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

• complete decomposition giving mainly the isoindigo derivatives 9a–e. Similar issues were observed when the secondary or tertiary thiobenzamides 3a–i or 4a–c were used. The following Scheme 2 summarizes the main possible reaction routes starting from 3-bromooxindoles 1a–e and various primary, secondary, and

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• (Table 1, entries 1–4), only the CoNPs/MgO catalyst gave a modest 28% conversion to the desired epoxide 2a (Table 1, entry 2) together with undesired formamide byproducts, probably coming from DMF decomposition under the reaction conditions. Then, we decided to use acetontrile (MeCN) as the solvent with

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

• CF3− to K+, preventing decomposition into CF2 and KF. The isolated CF3 is rather naked with a highly nucleophilic character, which is suitable for nucleophilic trifluoromethylation reactions. The K+ and glyme combination is particularly useful for the nucleophilic trifluoromethylation of carbonyl

• . Trifluoromethyl ketones. a) Hydrolysis of trifluoromethyl ketones. b) Selected examples of biologically active trifluoromethyl ketones. Chemistry of the CF3 anion generated from HCF3. a) Decomposition of the trifluoromethyl anion to difluorocarbene and fluoride. b) A hemiaminaloate adduct of CF3 anion to DMF. c

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• N2) [63] is the driving force for the decomposition of 47, generating collaterally bis(trifluoromethyl)-substituted carbenium ion intermediate 48fOTf. Finally, triflate 45f is formed after ion pair recombination (Scheme 11). Similar experiments conducted with 18O-labeled 44 confirmed the proposed

• -tert-butyl alcohol (Scheme 14) [63]. No further decomposition was observed in this case, suggesting that the especially challenging perfluoro-tert-butylcarbenium ion 55 cannot be generated. Highly deactivated bis(trifluoromethyl)-substituted carbenium ions and their precursors were also explored in

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

• the avoidance of gaseous byproducts [49]. Other mild sources of difluorocarbene include trifluoro(trifluoromethyl)silane (CF3SiF3 [50]) and difluorotris(trifluoromethyl)phosphorane ((CF3)3PF2 [51]). Difluorocarbene generation through the decomposition of hexafluoropropylene oxide upon heating

• : Hexafluoropropylene oxide (HFPO, 41) is an effective and cheap reagent for the difluorocyclopropanation of simple alkyl- and aryl-substituted alkenes [52]. It undergoes decomposition to form difluorocarbene (Scheme 16) at temperatures above 170 °C either under autoclave conditions or by gas-phase co-pyrolysis [53

• Difluorocarbene methods with organometallic sources Decomposition of phenyl(trifluoromethyl)mercury in the presence of sodium iodide: The preparation of difluorocyclopropanes using phenyl(trifluoromethyl)mercury (PhHgCF3, 45, Seyferth's reagent) as a source of difluorocarbene, results in good yields of the

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

• -one (4f). Unfortunately, after conducting this reaction, only trace amounts of 4f were obtained, and decomposition of the carbonyl compounds was observed. Thereafter, we explored the potential of the methodology for the ethyl 3-oxo-3-arylpropanoates 1l and 1m. When substrate 1l, containing an