Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• epimerisation. Amongst the many syntheses [53][54][55][56][57][58] of N-glycan oxazolines using this approach, the use of Lev protection on the donor, first developed by Boons [59], and then triflation and nucleophilic substitution by acetate aided by sonication, first developed by Fürstner [60][61], appear to

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• the unmasking of quenched or caged fluorophores by chemical reactions, such as the Staudinger reaction [98][99][100][101], hydrolysis [102] and group transfer mediated by nucleophilic substitution [103][104]. Optimizing the conditions requires a good balance between the affinity of the probe to the

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• , which in the presence of base (triethylamine or DBU) and trimethylchlorosilane transform into indolo[3,2-b]quinoline derivatives in moderate to good yields. Keywords: carbanions; cyclization; heterocycles; nitroarenes; nucleophilic substitution; silylation; Introduction The indolo[3,2-b]quinoline

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• reactions using a mixture of nucleophiles (for direct substitutions) and aryls (for Friedel–Crafts reactions) to give products 5–9. The nucleophilic substitution reactions of 1 are shown in Table 1 and Table 2, and were all conducted using either a mixture of water/isopropanol, or tris(hydroxymethyl)propane

• that some nucleophiles (such as N-methylbenzylamine and morpholine [not shown]) were unsuitable for this study, as the resulting products 7 could not be resolved in the 2H NMR with PBLG assay. Two different activator systems were investigated for the nucleophilic substitution of 1: a mixture of water

• by 2H NMR. Overall, the nucleophilic substitution of 1, using either of the described hydrogen bond activating systems, afforded enantioenriched benzylated products with little erosion in stereointegrity. In contrast to the above nucleophilic substitutions, which all proceeded with good

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• –S bonds were developed and already excellently reviewed, including nucleophilic substitution reactions between S-nucleophiles and organic electrophiles, metal-catalyzed C–S bond formations and organocatalytic or enzymatic approaches [15][16][18][20][21][22]. This review provides a brief overview

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• ligand exchange properties. A two-phase Brust–Schiffrin method (BSM) [49] was first used to synthesize decanethiol-stabilized AuNPs. These particles were then reacted with 11-bromo-1-undecanethiol to replace some of the decanethiol ligands with Br-terminated undecanethiol ligands (Scheme 2). Nucleophilic

• substitution by reaction with NaN3 then resulted in AuNPs with mixed monolayers containing 52% N3- and 44% CH3-terminated alkanethiol ligands. A series of alkynes were synthesised, including derivatives of nitrobenzene (1), ferrocene (2), anthracene (3), pyrene (4), aniline (5), and polyethylene glycol (6) all

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• -dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms. Keywords: anesthetics

• compound 4, originating from intramolecular nucleophilic substitution, was obtained as a byproduct in 25–30%. Noteworthy, compound 4 is formed as the only product when 1a is treated with organometallic reagents [48][49][50]. When the photoreaction was repeated in a 1:1 mixture of acetone and pH 7 buffer at

• File 1). Notably, irradiation of N-(bromomethyl)phthalimide (1c) in the presence of phenylacetate (2a) did not furnish the desired addition product, but the benzylated ester 5 in 37% yield instead (Scheme 4). The electron-withdrawing character of the phthalimide group favored thermal nucleophilic

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• described (Scheme 41). Depending on the structure of the nucleophile used, the salts either convert into resonance-stabilized, relatively stable ylides 62 or undergo intramolecular nucleophilic substitution with the triphenylphosphine departure to form products 63. The latter usually undergo further

• , generated easily in situ from acetylenedicarboxylic acid diester, triarylphosphine and a nucleophile. Depending on the structure of the nucleophile used, the salts convert into the corresponding resonance-stabilized, relatively stable ylides or undergo intramolecular nucleophilic substitution with

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• probed by DFT calculations. Keywords: chlorination; copper mediated perfluoroalkylation; crystal structure; DFT calculations; fluorous; hypervalent iodine; nucleophilic substitution; polar space group; Introduction A number of fluorous alkyl iodides, usually of the formula RfnCH2CH2I or RfnI (Rfn = CF3

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• as colorless crystalline solids. It is assumed, that the undesired side products 9k and 10k were formed by a ligand transfer from the Lewis acids to imine 5k. Nucleophilic substitution of N/O-acetal 9k with two equivalents of (trimethylsilyl)ethynyllithium, in analogy to the conversions reported by

• to avoid nucleophilic substitution of the halide at a late stage, we decided to start the synthesis with 4-azidobutanal, which was prepared by opening THF with iodine and NaBH4, nucleophilic substitution by sodium azide and Swern oxidation of the alcohol. 4-Azidobutanal was converted with chiral

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• ) followed by a formal [4 + 1]-annulation reaction with ylide (tandem Michael addition/intramolecular nucleophilic substitution of dimethylsulfide by oximate anion in intermediate 94). The addition of sulfonium ylides to nitrosoalkenes can end up not only with cyclic products, but also with α,β-unsaturated

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• could consist in a nucleophilic substitution (SN2) involving chloride ions as nucleophilic species to produce the intermediate II. Then, a repetition of this mechanism yields phosphonic acid. The preponderant route is likely governed by the stability of the carbocation and the steric hindrance around

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• , France Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France 10.3762/bjoc.13.217 Abstract Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution

• aminolysis. This strategy has been extensively used [1], involving milder conditions and provides access to unsymmetrical dipeptides and DKPs. Furthermore, substituted prolines could be obtained by nucleophilic substitution of benzylamine from dimethyl dibromoadipate, allowing the addition of functional

• groups on the Pro–Pro-based framework [17]. Recently, mechanochemistry has become a powerful synthetic technique for making new organic molecules [18][19]. In the course of this project, we applied mechanochemistry to a nucleophilic substitution and the efficient coupling of two proline residues. Results

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• spectroscopy to investigate how the choice of base influences the course of a base-catalysed nucleophilic substitution reaction [39]. Raman spectroscopy is particularly well-suited for monitoring and tracking organic reactions. It is a generally accessible and inexpensive, with an output based on changes to

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• , respectively. On the other hand, two nucleophilic substitution reactions using phenol and morpholine gave the expected heterocycles 10 and 11 in 73% and 23% yields, respectively. Conclusion In summary, we developed a short and completely regioselective method for the synthesis of imidazo[1,2-a]-N-heterocycles

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• ) (Cp′ = C5Me4(n-Pr)). Mechanochemical synthesis of the Ar-BIAN ligands and indium(III) complexes (top). One-pot synthesis of an indium complex (bottom). Synthesis of germanes from germanium (Ge) or germanium oxide (GeO2). Ball-milling nucleophilic substitution reactions to produce acyclic and cyclic

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• in 1:1 ratios – were always formed, which is a serious drawback of this approach. Another well-known method based on retrosynthetic disconnections at the same C–C bond employed intramolecular vicarious nucleophilic substitution of hydrogen in the substituted N-(3-nitrophenyl)chloromethylsulfonamides

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• effect on the nucleophilic reaction. Keywords: cyclodextrins; milling parameters; nucleophilic substitution; planetary ball mill; Introduction Their hollow structures make cyclodextrins (CDs) a class of carbohydrates that can form inclusion complexes with organic molecules, inorganic salts and complex

• . The reaction was performed in a planetary ball mill and the processing parameters were systematically varied with the aim of pointing out their influence on the nucleophilic substitution reactions in terms of rate and yield. Specifically systematic variation involved rotation speed, milling tool

• the reactor, the nucleophilic substitution with NaN3 was performed using glass reactors 2 and 25 mL in volume and the same number of balls of equal size (30 balls of 1 mm in diameter). The experimental findings are summarized in Figure 1 and Supporting Information File 1, Table S1 entries 18 and 19

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• advantages when compared with other conjugated aromatic systems [2][3][4]. First of all, 9H-carbazole is a relatively cheap starting material. At the same time, its fully aromatic system renders this heterocycle a good chemical and environmental stability. Nucleophilic substitution of a 9H atom proceeds

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• substituted o-phenylenediamine 11. Sakata et al. reported an interesting one-pot procedure yielding 6-substituted SYN quinoxalin-2(1H)-ones from substituted N-(2-nitrophenyl)-3-oxobutanamides [28]. Another example for preparation of the desired regioisomer starts from the nucleophilic substitution of o

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• of diselenides as starting reagents, under an oxygen atmosphere and using PEG 200 as the solvent. This procedure involves the in situ generation of dialkyl diselenides through a K3PO4-assisted reaction of an alkyl selenocyanate obtained by a nucleophilic substitution reaction between KSeCN and alkyl

• acetylenes. Keywords: alkynyl selenide; electrophilic cyclization; nucleophilic substitution; potassium selenocyanate; terminal alkynes; Introduction Alkynyl selenides, as many other selenium compounds, have potential anti-oxidant activities, and may play a role in certain diseases such as cancer, heart

• three-step one-pot procedure using KSeCN (2), alkyl (3) and styryl halides (4) with good yields (Scheme 1, A) [38]. This reaction proceeds through an initial nucleophilic substitution reaction between the alkyl halide and KSeCN to afford the corresponding alkyl selenocyanate (RSeCN). The treatment of

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• Bu, the nucleophilic substitution of the fluorine atom at the para position to boron is the predominant route. When R = Ph, the ratio M[4-RC6F4BF3]/M[2-RC6F4BF3] is ca. 1:1. Substitution of the fluorine atom at the ortho position to boron is solely caused by the coordination of RLi via the lithium

• atom with the fluorine atoms of the BF3 group. This differs from the previously reported substitution in K[C6F5BF3] by O- and N-nucleophiles that did not produce K[2-NuC6F4BF3]. Keywords: C-nucleophile; NMR spectroscopy; nucleophilic substitution; pentafluorophenyltrifluoroborate; Introduction

• alkoxydefluorination of K[C6F5BF3] with the corresponding O-nucleophiles RONa or ROK [31]. The nucleophilic substitution of a fluorine atom in K[C6F5BF3] with sodium (potassium) azolides in polar aprotic solvent (DMF, DMSO) at 100–130 °C resulted in K[4-R2NC6F4BF3] (R2N = pyrrolyl, pyrazolyl, imidazolyl, indolyl, and

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• nucleophilic substitution [39]. In 2015, the Chae group found difunctionalized ethanes including 2-dimethylaminoethanol and ethylene glycol can function as ligand to work with Cu(OAc)2 in the presence of KOH, affording phenols from aryl iodides in moderate to excellent yields (Scheme 17) [40]. In 2010, a

• of these specific precursors often needs laborious work. The direct nucleophilic substitution of aryl halides with sodium alkyl sulfate was considered a simple strategy for the synthesis of aryl thiols [90][91][92]. However, these non-catalyzed conversions require excess amounts of sodium alkyl

• converted in situ to aryl thiols through C–S bond cleavage by an intramolecular nucleophilic substitution. The protocol tolerated a broad range of functional groups such as amino, hydroxy, trifluoromethyl, ester, carboxy and formyl groups. As described above, although it seems more difficult to develop an