Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• at C4 could contribute to a new fluorine effect in nucleophilic substitution. Finally, with the continuous objective of synthesizing novel multi-vicinal fluorosugars, we prepared one difluorinated and one trifluorinated alditol analogue. Keywords: deoxyfluorination; Et3N·3HF; fluorine effect

• exclusively products with inversion of configuration, although in a lower yield for compound 18. These results highlighted the likely influence of the stereochemistry of the fluorine atom at C2 in particular when we compared the reactivity between compounds 13 and 16. The nucleophilic substitution with

• simple Et3N·3HF with or without addition of triethylamine. The role of the reagent and the remote influence of the fluorine atom at C2 on reactivity at C4 could concomitantly contribute to a new fluorine effect in nucleophilic substitution [49]. Finally, the synthesis of two distinct polyfluorinated

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• obtained through nucleophilic substitution reactions between BImNs (N = 4, 10, 12, 14) and 3. All synthesized compounds were characterized by NMR spectroscopy and high-resolution mass spectrometry. Self-assembly properties of PBImNs in aqueous buffer The self-assembly properties of the four PBImN

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• . Azopyridines 14, 16 and 18 were prepared by nucleophilic substitution with 2-methylpropane-2-thiol (13) and methyl 3-mercaptopropionate (15) as nucleophiles (Scheme 2). 3-(3-Bromophenylazo)-4-cyanopyridine (20) was directly obtained by conversion of 3-amino-4-cyanopyridine (19) and 3. Alkaline hydrolysis as

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

• have also reported the functionalized sumanene derivatives 73–75 at the convex side of the internal carbon commencing from the bromination of the hydroxysumanene 68 using NBS and subsequent nucleophilic substitution reaction [47][48]. To their surprise, when they used molecular bromine instead of NBS

• 74 into the stable derivatives 75 having a strong C–C bond through the nucleophilic substitution reaction with phenol and anisole in the presence of trifluoromethanesulfonic acid (TfOH) with total stereoinversion. This suggests that the nucleophile attacks occur from the concave face of the π-bowl

• [48]. Although, for the nucleophilic substitution reaction with phenol derivatives, they have tried several reaction conditions including the amount of acid as well as phenols. After several experimentations, they found that 30 equivalents of phenol and 1 equivalent of TfOH at 0 °C provided the best

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• nucleophilic substitution and then methylated. NDI 4 could be isolated in a yield of 60% after purification by column chromatography. In the last synthetic step, the molecule was triply methylated with iodomethane in acetonitrile at room temperature for three days. After complete methylation, purification by

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• carbanions or alcoholates was also attempted but the starting bromide E-1d degraded under these conditions. Finally, this expeditious synthesis of tetrasubstituted fluoroalkenes by sequential ring-opening and nucleophilic substitution reactions was applied to test the robustness of a selective preparation of

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• ][3]. As part of our ongoing research in DES chemistry, we reported recently on the preparation of valuable heterocycles by (a) nucleophilic substitution (tetrahydrofuran derivatives) [4], (b) heterocyclodehydration reactions (2-aminoimidazoles, 2-pyrazinones, benzoxazines, thiophenes) [5][6][7][8

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• (6) [23][24]. In contrast with bromobenzene, hexafluorobenzene (7) is sufficiently reactive in nucleophilic substitution reactions, and thus the synthesis of 2-(perfluorophenyl)malonate (3) is straightforward. A synthesis of diethyl 2-(perfluorophenyl)malonate (3) was first described in patent

• -fluorophenyl)-2-methylmalonate (9) [32], diethyl 2-(3-fluorophenyl)-2-methylmalonate (10) [33], and diethyl 2-(4-fluorophenyl)malonate (11) [6][32] (Figure 2) with minor variations in the alkali concentration and temperature. No nucleophilic substitution of activated fluorine atoms or other side reactions were

• with the formation of acid 12. The nature of these byproducts was not analyzed. Probably, they are formed by nucleophilic substitution of fluorine atoms in the perfluorophenyl moiety. Acid 12 is fairly soluble in water and the separation of reaction products is cumbersome (see Supporting Information

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

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• nucleophilic substitution reaction (SNAr) by transit the sulfur anion in 9 followed by dismissal of the nitrite ion may result in the formation of the β-carboline-tethered benzothiophenone derivative 2bA. It is anticipated that the role of DMSO is to stabilize the ionic intermediates, specifically 10 and to

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

• a multistep synthesis route. A first approach relied on the nucleophilic substitution of chlorine in cyanuric chloride with Grignard reagents, ammonia or amines [25][26], which suffered from the high reactivity of the Grignard reagents that prevents further functionalization. Moreover, this protocol

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

• corresponding mesylate 38b proved sufficient for the synthesis of N-tethered substrates 37 (Z = NTs), through simple nucleophilic substitution (via c). It is noteworthy that under standard PK reaction conditions, fluoroenyne 39 evolves to diene 40. The formation of compound 40 is possible by elimination of HF

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

• best of our knowledge, there were no reports on using BTMS for the nucleophilic substitution of alkyl chlorides. A similar exchange reaction was reported only for 2-chloropyridines [51], and required harsh reaction conditions, such as heating at 90–100 °C for 100 h. In this study we investigated the

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• intramolecular nucleophilic substitution followed by an intermolecular nucleophilic displacement with the in-situ generated 1-thiabicyclo[1.1.0]butan-1-iums 399 as key intermediates. Following this route, 3-substituted thietanes 400 were prepared from reactions of 2-(1-chloroalkyl)thiiranes 398, especially

• generated thiolate in the zwitterionic intermediates 427 then further underwent an intramolecular nucleophilic substitution to yield the desired thietanes 425 by loss of a molecule of DMSO [22] (Scheme 94). 4.1.3 Synthesis via electrophilic ring expansion of thiiranes: To realize the synthesis of

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• -trans relative configuration. The resemblance between 3-hydroxypyrrolidines 1 and 4-hydroxyisoxazolidines 2 (Figure 1) makes the latter valuable structural fragments in drug discovery [13][14][15][16][17][18]. Up to now, this class of compounds was commonly prepared using intramolecular nucleophilic

• substitution reactions of properly substituted hydroxylamines [19][20] and N-hydroxyphthalimides [21][22][23][24] as well as by Tamao oxidations of 4-silylisoxazolidines [25][26]. Very recently, Tomkinson et al. described a simple and effective method for an intramolecular oxyamination of allylic N-tosyl

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• electron-withdrawing substituents decreases it (example 82e, 64%). Non-aromatic oximes of chloro- or bromoacetone are not suitable for this method; product 82f was observed in trace amounts. According to the proposed reaction pathway, the nucleophilic substitution of the halogen atom with the formation of

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• an electron acceptor in donor–acceptor systems [14]. The target compounds were obtained by nucleophilic substitution reaction of the intermediate quinazoline derivative Q1 with the corresponding donor compounds. The chemical structures were characterized by 1H NMR, 13C NMR, ATRIR spectroscopy and

• compounds 1–3 were synthesized through nucleophilic substitution reactions between quinazoline derivative Q1 and the respective donor compound in the presence of sodium hydride in dry dimethylformamide (DMF). The reaction mixtures were refluxed for 24 h. After completion of the reactions, the reaction

• ): Quinazoline derivative (Q1, 0.25 g, 0.79 mmol), 3,6-di-tert-butylcarbazole (0.48 g, 1.7 mmol) and sodium hydride (0.50 g, 1.6 mmol) in dry dimethylformamide (DMF) were used for the nucleophilic substitution reaction. The title compound was obtained as yellowish crystals in a yield of 0.25 g, 37%; Tm = 181 °C

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• on a Sandmeyer thiocyanation reaction followed by a Langlois-type nucleophilic substitution of the cyano group by the CF2PO(OEt)2 residue [55]. Several (diethylphosphono)difluoromethylthiolated products were obtained and this report further showcased the potential of using a copper-based reagent for

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• ], and borylation [32]), has been in great demand recently rather than the conventional multistep synthesis with nucleophilic substitution/cross-coupling via halogenation of BODIPYs [33] or from the activated precursors [34] via unstable pyrrolic intermediates. In particular, halogenation (e.g

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• the generation of sodium 1,3-thiaselenol-2-ylmethylselenolate from 1,3-thiaselenol-2-ylmethyl selenocyanate or bis(1,3-thiaselenol-2-ylmethyl) diselenide followed by nucleophilic substitution reactions. Sodium 1,3-thiaselenol-2-ylmethylselenolate underwent nucleophilic addition to alkyl propiolates in

• -thiaselenole; nucleophilic addition; nucleophilic substitution; rearrangement; seleniranium intermediate; Introduction The regio- and stereoselective synthesis of organoselenium compounds based on selenium-centered electrophilic reagents has been one of the most important and effective directions in

• represent a very interesting class of compounds with a wide range of synthetic applications [28][29]. The anchimeric assistance effect, also known as the participation of neighbouring groups, is usually considered mainly as a factor accelerating the rate of nucleophilic substitution reactions. At present

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• -dihydrothiazole (Scheme 8). These experimental results suggest that the reaction may proceed through a nucleophilic substitution rather than a radical pathway. On the basis of the results collected from the control experiments and previous works in the literature, a plausible mechanism for this KOt-Bu-promoted

• ring-opening N-alkylation is illustrated in Scheme 9. The reaction is proposed to begin with the generation of iminium ether A [27][28], generated from the reaction of 2-metyl-2-oxazoline with benzyl bromide in the presence of KOt-Bu with release KBr. A subsequent second nucleophilic substitution of

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• material for the synthesis of relevant groups of compounds, many of these synthetic procedures are based on nucleophilic substitution of the carbon chlorine bond. Oxidative or reductive activation of monochloroacetic acid results in radical intermediates, leading to reactivity different from the

• traditional reactivity of this compound. Here, we investigated the possibility of applying monochloroacetic acid as a substrate for photoredox catalysis with styrene to directly produce γ-phenyl-γ-butyrolactone. Instead of using nucleophilic substitution, we cleaved the carbon chlorine bond by single-electron

• glycine and diethyl malonate, are based on nucleophilic substitution of the chlorine [6][7][8][9][10]. In an attempt to find new synthetic applications of monochloroacetic acid we turned our attention to photoredox catalysis. We were inspired by the rebirth of visible light photoredox catalysis, induced

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• Preparation of N-heterocyclic phosphines via P–C bond formation Nucleophilic substitution of halogens There are different methods that have been reported for the construction of the P–C bonds. Two approaches are possible using halogenated precursors. The first one is the organometal-halogen-phosphine route

• nucleophiles compared to organometallic or metal phosphides generated through metalation processes. Hayashi et al. [66] used tris(trimethylsilyl)phosphine to control the nucleophilic substitution in the preparation of P,N-(phosphino)triazine ligands (Scheme 5). It was shown that the use of other nucleophiles

• and/or alkoxy derivatives 29–31. Selectively varying the molar ratio of the silylphosphine nucleophile and the starting reagent 25 resulted in the corresponding bis- and tris(diphenylphosphine)triazine motifs 27 and 28. A subsequent nucleophilic substitution reaction of 27 gave compounds 32 and 33

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• formed dication V underwent an intramolecular nucleophilic substitution through transition state VI, which proceeded with a small activation barrier, leading to the cyclic intermediate VII and further to the rearranged product 54. The tentative mechanism discussed above does not explain the formation of