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

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• macrocycles by Pd-catalyzed Buchwald–Hartwig amination [36]. Though this method is often preferable for the macrocyclization in comparison to classical nucleophilic substitution [28][31], it is limited to bile acid derivatives bearing groups with C(sp2)–Hal bonds. In addition, the use of bile acid moieties

• ). Consequently, this system was used for the synthesis of bis-steroidal arylamines 5a and 5b starting from 24-aminocholanol 3a. Activated chlorinated substrates, such as 1,8- and 1,5-dichloroanthraquinones, are very promising substrates for nucleophilic substitution. For instance, 1,8-dichloro-9,10-anthraquinone

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• corresponding 5′-selenocyanates in variable yields over the course of between one and eleven hours thereby avoiding the preparation and use of hygroscopic tetrabutylammonium salts. Keywords: ball mill; chalcogen; mechanochemistry; nucleophilic substitution; nucleoside; Introduction Nucleophilic displacement

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• time of 120 h to completely convert the allyl alcohol 1a into the phosphonate 2a in 45% yield (Table 1, entry 3). The nucleophilic substitution of alcohol 1a with triethyl phosphite in THF at reflux was significantly less effective (Table 1, entry 4). The TLC and 1H NMR analyses of the crude reaction

• nucleophilic substitution reaction worked also well and gave the allylphosphonate 4a in 90% yield within 1 h (Table 3, entry 1). More interestingly, repeating this reaction without DMAP and under solvent-free conditions at 80 °C gave, in only 30 min, the phosphonate 4a in 92% yield (Table 3, entry 2

• -hydroxyphosphonates may display interesting biological activities [51][52]. The next step was to realize the nucleophilic substitution of the γ-hydroxyphosphonate 5a with a variety of differently substituted tosylamines catalyzed by 15 mol % of iodine [53] in refluxing methylene chloride. Under these optimized

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• introduction of the methylseleno moiety was performed by nucleophilic substitution of the α-bromide in 5 with methylselenol obtained by in situ reduction of dimethyl diselenide with NaBH4 [23]. The obtained crude methyl β-selenofucoside was anomerized under Lewis acid catalysis to give the anomeric mixture in

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• nucleophilic substitution mechanism: the higher the electronic density on the carbinol C atom, the higher the reaction rate. When the electronic density is somewhat lower, competitive formation of the ether occurs but subsequent nucleophilic addition of the thiol to the ether restores a very high selectivity

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• occurs during the attack of the sp2 hybridized N-1 atom of the pyrimidine base to the anomeric C-1 carbon atom of α-D-PF-1P in the nucleophilic substitution of phosphoric acid residue of the latter catalyzed by E. coli UP and TP. It was unequivocally proven by the physicochemical and theoretical methods

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• . Only when treated with hydrazine, nucleophilic substitution was observed and after reduction with Raney nickel the desired 3-deazaadenosine was isolated. Our own attempts towards direct ammonolysis failed as well. Additionally, the limited commercial availability of hydrazine and its inconvenience in

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• compounds has been well documented [3]. The predominant site of reactivity is at the electrophilic β-carbon, which results from the combined influence of the amide and chloro substituents, mitigating the electron-donating effect of the sulfide moiety. Nucleophilic substitution [4], Diels–Alder reactions [5

• the β-chloroacrylamide cascade was not investigated. Furthermore, the potential vulnerability of α-thio-β-chloroacrylamides towards nucleophilic substitution by an aqueous ethanol component of the reactant stream (from α-thioamide 2 preparation), particularly at elevated temperatures, strongly

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• generate a π-allylpalladium intermediate I that further undergoes a nucleophilic substitution reaction with the β-keto ester carbanion derived from 2j, affording the monoallylated compound 3j. The conversion of the keto ester 3j into the tricyclic product 6j was further performed through an intramolecular

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• millimolar scale, they are easily scalable. Keywords: green chemistry; nucleophilic substitution; planetary ball mill; siRNA delivery intermediate; sugammadex; Introduction Cyclodextrins (CDs) are cyclic α(1→4)glucopyranosides and have been fully described in a number of publications [1][2][3]. They are

• simplicity and flexibility [18][19][20][21]. While the mechanochemical manipulation of covalent bonds is hardly a brand new concept, its diffusion into carbohydrate chemistry, and particularly into CD derivatization, has been rather slow [22][23]. The ability of HEBM to favour the nucleophilic substitution

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• synthesized by nucleophilic substitution of the ethoxy group of (CO)5W=C(OEt)Fc (M(CO)5(1Et)) by ferrocenyl amide Fc-NH– (Fc = ferrocenyl). W(CO)5(E-2) thermally and photochemically eliminates bulky E-1,2-diferrocenylimine (E-3) via a formal 1,2-H shift from the N to the carbene C atom. Kinetic and

• complexes [16][17]. First representatives of multimetal carbene complexes M(CO)5(1R) bear α-ferrocenyl alkoxy carbenes :C(OR)Fc (1R, M = Cr, Mo, W; R = Me, Et; Fc = ferrocenyl) [18][19][20][21][22]. Nucleophilic substitution of the alkoxy substituent OR by amines gives access to α-ferrocenylamino Fischer

• of ferrocenyl carbene complexes has been extensively investigated [25][26][27][34][35][36][37][38][39]. A second ferrocenyl unit can be incorporated by employing aminoferrocene (Fc-NH2) [40][41] in a nucleophilic substitution reaction [27]. The trimetallic complex Cr(CO)5(E-2) with the

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• contains a cysteine residue at position 545 for conjugation [31], an NHC ligand containing a maleimide function was prepared (Scheme 1). The imidazolium salt 3 was synthesized by nucleophilic substitution of mesityl imidazol 1 with maleimide derivative 2. These salts were used to generate the Cu(I) NHC

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• converted to diethyl (2-methyl-2-pyrrolidinyl)phosphonate 48 by ring closure through an intramolecular nucleophilic substitution (Scheme 12). Subsequent oxidation of 48 with m-chloroperbenzoic acid afforded the corresponding N-oxide 49 which was used for the in vitro and in vivo spin trapping of hydroxyl

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• prepared from 3-chloropivaloyl chloride (3) by amide formation and subsequent cyclization with the Burgess reagent (methyl N-(triethylammoniumsulfonyl)carbamate) using standard procedures (Scheme 2). Subsequent nucleophilic substitution with KPP2 in refluxing THF proved to be much faster than the analogous

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• activation; chiral catalysis; diazo compounds; total synthesis; Introduction One of the major challenges met in organic synthesis is the formation of carbon–carbon bonds, in particular in a stereoselective way. Nucleophilic substitution reactions, radical reactions, cross-coupling reactions and the Heck

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• Bu4NBr resulted in bromohydrine 47, followed by levulinyl (Lev) protection of the hydroxy group (product 48). Nucleophilic substitution at the 6'-position with Bu4NN3 gave the naturally occurring (5'S,6'S)-stereochemistry of the uridine core structure in a double inversion manner [78][99]. DDQ oxidation

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• - and stereoselective introduction of both fluorine and nitrogen (as an azide) by nucleophilic substitution before acetolysis of the 1,6-anhydro bridge. The characteristic feature of the synthesis is the introduction of fluorine at C-3 by the reaction of D-gluco-configured 3-hydroxy derivatives with