Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• important method in the synthetic toolbox for anomeric modification of sugars and glycoconjugate preparation. Left: The Mitsunobu reaction is essentially a nucleophilic substitution of alcohols occurring with inversion of configuration at the alcohol stereocenter. The auxiliary reagents are involved in a

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• , Slovakia 10.3762/bjoc.14.115 Abstract The aromatic nucleophilic substitution reaction based synthesis of a three-armed cryptand displaying 2,4,6-triphenyl-1,3,5-triazine units as caps and pyridine rings in the bridges, along with NMR, MS and molecular modelling-based structural analysis of this compound

• are reported. Appropriate NMR and molecular modelling investigations proved the formation of 1:1 host–guest assemblies between the investigated cryptand and some polynuclear aromatic hydrocarbons or their derivatives. Keywords: aromatic guests; aromatic nucleophilic substitution; cryptand; NMR

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• intermediate (path A). Alternatively, the benzyl radical formed in situ couples with the iodanyl radical to give the pseudo halide, benzyl-λ3-iodane, which is more reactive to nucleophilic substitution by a carboxylic acid [77][78]. Another possible course of the reaction mechanism assumes the formation of a

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• subsequent 5-exo-type cyclization by nucleophilic attack on the iodonium then leads to the isoxazoline or pyrazoline cores (C) bearing the hypervalent iodine(III) group. Following iodine activation by the Lewis acid, the iodonium ion D undergoes nucleophilic substitution with excess acetonitrile to form

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• -catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc). Keywords

• -diethyl tartrate (L-DET) directing the reaction towards the D-galacto-configured epoxythreitol 5a. Alternatively, epoxidation of 4b with D-DET was used to access L-galacto-configured epoxythreitol 5b. A procedure by Miyashita et al. [19] for nucleophilic substitution of epoxides by an azide functionality

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• syntheses have contributed to structural diversity and drug discovery efforts. Convergent and modular approaches to synthesis have garnered much attention in this regard. Among them nucleophilic substitution at C1' has seen wide applications providing flexibility in synthesis, good yields, the ability to

• that is also based on the nucleophilic substitution of ribonolactone. Review Nucleophilic addition to D-ribonolactone and its stereochemistry Two prominent methods of C-nucleoside syntheses involve either i) the linear construction of a (hetero)aryl moiety on a C1'-functionalized ribose or ii) coupling

• ascribed to the modular nature of syntheses that allows for simultaneous alterations in the sugar and the nucleobase to generate diverse analogues in a facile manner. Within this approach, nucleophilic substitution of ribonolactone (Figure 6A) has garnered much attention [61][62][63][69][70][71][72][73][74

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• intermediate. The functionalities required for the secondary transformations like the leaving group (-Cl) for nucleophilic substitution, alkyne and azide for IAAC can be assembled via the Ugi reaction (Scheme 1). Results and Discussion We initiated our studies with the Ugi 4-component reaction of o

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