Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• , enantiospecific nucleophilic displacement reactions [66][67]. α-Fluorinations The stereoselective electrophilic α-fluorination of carbonyl compounds became a thoroughly investigated field over the course of the last 15 years [68][69][70][71][72]. A variety of different catalytic approaches, either relying on the

• ][101]. Several strategies to access these valuable motives in an enantioenriched fashion have been reported in the past. One option would be to use already α-functionalized (i.e., halogenated) carbonyl compounds and carry out functional group interconversions, like, e.g., stereospecific nucleophilic

• displacement reactions [87]. Another powerful strategy would be the use of prochiral α-halocarbonyl compounds for asymmetric Darzens-type reactions to obtain chiral α,β-epoxycarbonyl compounds, which has been rather successfully demonstrated under chiral phase-transfer catalysis in the past [18][102][103][104

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• transformations as well. Under the same conditions but using a C2–OH sugar, the corresponding isolatable 1,6-anhydrosaccharide is formed in good to excellent yield [71]. The authors proposed as the intermediate species the unstable 1,2-anhydrosaccharide resulting from nucleophilic displacement of the activated

• to provide the 1,2-trans β-diastereomer. Only in pathway A, by direct nucleophilic displacement of the β-activated complex, does the minor α-diastereomer form. To demonstrate the potential utility of this methodology in labeling strategies, the Shoda group has also accessed fluorescent thioglycosides

• displaced by the 2-acetamido group to provide the observable oxazoline prior to nucleophilic displacement by the azide, N3−. Due to neighboring group participation, only the β-anomer is observed. In a 2014 follow-up study using C2–OH GSH donors, the Nitz group reported that, in fact, the anomeric ratio (α:β

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

• University, Department of Chemistry, Lower Mountjoy, Stockton Road, Durham DH1 3LE, UK 10.3762/bjoc.13.11 Abstract Vibration ball-milling in a zirconia-lined vessel afforded clean and quantitative nucleophilic displacement reactions between 4-methoxybenzylthiolate salts and nucleoside 5′-halides or 5

• 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

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• length via stereospecific nucleophilic displacement of the chiral auxiliary with complete inversion of configuration at the sulfur center [46][47]. Sulfoxide 3 is incorporated into the catalyst via a [3 + 2] oxidative cycloaddition with allylruthenium complex 4. Desilylation of cationic complex 5, ion

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• imidazolones to nitroalkenes are shown by the transformations depicted in Scheme 4. Thus, nucleophilic displacement of the thioether group gives access to various types of heterocycles of interest in medicinal chemistry [66][67] (i.e., imidazolidinones 19 and 20, 2-arylimidazolone 22, 2-aminoimidazolone 23 and

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

• previous results from our [24] and other groups [25][26][27][28], we designed an approach based on stereoselective introduction of an azide as a masked amine group at C-2, and fluorine at C-3 and C-4 by nucleophilic displacement. Resulting 3-fluoro, 4-fluoro, and 3,4-difluoro analogs of 2-azido-1,6

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• in gram scale preparations and so the prepared compounds need further purification steps. Additionally, these environmentally unfavorable solvents present other disadvantages; both in their decomposition and toxicology profile. A study of the nucleophilic displacement of 6-monosubstituted β-CDs and

Amino-functionalized (meth)acryl polymers by use of a solvent-polarity sensitive protecting group (Br-t-BOC)

• Helmut Ritter,
• Monir Tabatabai and
• Markus Herrmann

Beilstein J. Org. Chem. 2016, 12, 245–252, doi:10.3762/bjoc.12.26

• explained above, the protecting group undergoes a polar solvent driven intramolecular nucleophilic displacement (Figure 1). In contrast, in nonpolar solvents such as benzene, toluene, chloroform (CHCl3) or dichloromethane (CH2Cl2) 3a,b are very stable, whereas in polar protic solvents such as ethanol (EtOH

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• benzylated using BnBr and NaH in DMF to afford 3a (Scheme 1). Further, the C6-tosyl intermediate was converted into 6-azido-6-deoxy-1,2;3,4-di-O-isopropylidene-β-D-psicofuranose (4a) by a nucleophilic displacement of the C6-O-tosylate with NaN3 in DMF at 70 °C [48]. The spectral data and the specific

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• acids are known to undergo acid and alkaline hydrolysis at rates 105–108 times faster than their acyclic analogs [17]. Thus, cyclic esters may be regarded as a halogen equivalent in terms of their leaving group ability under nucleophilic displacement conditions [18]. The rapid hydrolysis of 2-methoxy

One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2015, 11, 1265–1273, doi:10.3762/bjoc.11.141

• reaction of thiourea with benzoic anhydrides, which were subjected to conjugate addition with electron-deficient alkenes or a nucleophilic displacement reaction with alkyl halides. Keywords: benzoic anhydride; Michael addition; nucleophilic displacement; thioester; thiourea; Introduction Thioesters have

• -based reactions have a foul smell, making them unpleasant. Thioesters can also be prepared through the conjugate addition and nucleophilic displacement reactions using thioacid nucleophiles. Nevertheless, the reactions of thioacids have not been widely studied because they are not sufficiently available

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• nucleophilic displacement at the 3'-position of the 3'-xylo intermediate with azide as a nucleophile [61][62][63][64][65]. We have found that robust results for this reaction could be achieved by activation of the 3'-hydroxy group as a mesylate, followed by treatment with sodium azide in DMF at elevated

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• Lisa F. Becker Dennis H. Schwarz Gerhard Wenz Organic Macromolecular Chemistry, Saarland University, Campus C4.2, 66123 Saarbrücken, Germany 10.3762/bjoc.10.310 Abstract Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic

• displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• phosphonamides: (A) Arbuzov reaction, (B) condensation of diamines with phosphonic acid dichlorides, (C) nucleophilic displacement, and (D) alkylation of 2-oxo-1,3,2-diazaphospholidine (Scheme 9). All of these methods were employed to prepare the phosphonamide reagents used in the synthesis of the natural

• an unsymmetrical phosphonamide of type 64 was used in the synthesis of PTP inhibitors [68], and methyl jasmonate [48], as discussed later in this review. Nucleophilic displacement The stereoselective synthesis of unsymmetrical phosphonamides 67 by nucleophilic displacement was reported by Hua and co

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• formation of aminonitrile from acetaldehyde. A short-cut path by the nucleophilic displacement and the concomitant proton transfer. “The first bypass” in Scheme 5. A contrast of the nucleophilic addition. Elementary processes of the acid-catalyzed hydrolysis of 2-amino-propanonitrile. Summary of the present

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• nucleophilic displacement of the halogen at the phosphorus atom of a halophosphine with a metal acetylide. Grignard

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• , nucleophilic aromatic substitution reactions of halopyrimidines are smooth and high-yielding, especially when an electron-withdrawing group is present in this heterocycle. It is noteworthy that in the case of non-activated dihalopyrimidines, the first nucleophilic displacement reaction deactivates the

• facilitates a very useful and convenient synthetic possibility for the preparation of pyrimidinediamines [16] or 5-nitroso-4,6-pyrimidinediamines. An N-nitroso moiety, which assisted the nucleophilic displacement reaction, does not require harsh reaction conditions and it is a high-yielding process. The

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• with [18F]fluoride, an alternative procedure to afford 3 was envisaged. Esters of sulfonic acids can be also prepared by nucleophilic displacement of carbon-bound halogens with sulfonates, which works best with alkyl iodides and silver salts of sulfonic acids [23]. Therefore, the required 3-iodopropyl

Molecular solubilization of fullerene C₆₀ in water by γ-cyclodextrin thioethers

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1644–1651, doi:10.3762/bjoc.8.188

• procedures Hydrophilic thioethers 1–7 at all primary carbon atoms of γ-CD were synthesized from octakis(6-deoxy-6-iodo)-γ-CD by nucleophilic displacement reaction with sulfur nucleophiles by using standard procedures described previously [38]. Phase-solubility investigations Solubility measurements of C60 in

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• analysis [35]. Nevertheless, subsequent cross-coupling reactions under palladium catalysis were successfully achieved. Similarly to the Passerini reaction, it was hypothesized that the crucial transmetalation step proceeds throught a nucleophilic displacement of the halogen from the σ-arylpalladium complex

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• /heteroaryl substituted 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates. The synthesis of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters was carried out by nucleophilic displacement by aziridine of the chloro atom from electron-poor activated 2-(1-alkyl/aryl/heteroaryl-1

• carbanion during the nucleophilic displacement of the iodo leaving group (Table 2, entries 1 and 5). It was also observed that in the presence of electron withdrawing groups on aryl rings, the rate of iodide ion mediated aziridine ring expansion to pyrrolines was slow compared to N-vinylaziridines bearing

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• tertiary thiols 57 directly (Scheme 21), with only the electron rich para-methoxyphenyl substituent performing poorly. As with stereospecific nucleophilic displacement, only specific substrates are tolerated in conjugate additions, and further functionality is always required to activate the electrophilic

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• the azido derivative 3 in almost quantitative yield, by nucleophilic displacement of the chlorine atom by azide ion. Deprotection of the latter under Zemplén conditions [17] afforded the expected derivative 4 in quantitative yield (Figure 1). The copolymer backbones, namely the poly(propargyl acrylate

Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• step however, on switching to L-selectride for the stereoselective reduction [26], the allosamine derived thioglycoside 10 was obtained in good overall yield. For an alternative route, 7 was transformed into the 3-O-triflate 9 and then subjected to nucleophilic displacement with sodium nitrite in the

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• , Chiara and co-workers have described a novel complementary approach in which the oxazoline ring is generated by SN2 nucleophilic displacement reaction from the β-hydroxyurea 30 via the triflate intermediate 31 (Scheme 3) [65]. A similar methodology was used by the same authors to prepare the trehazolin