Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• trifluoromethyl group. It must be noted that this methodology represented the first efficient and general preparation of chiral β-trifluoromethyl β-amino acid derivatives containing a quaternary stereocenter adjacent to the amine function. In 2014, Linclau and Poisson reported the synthesis of chiral α,α-difluoro

• -butylsulfinyl)amino]-2-oxoindolin-3-yl}acetates 33a–m exhibiting a quaternary stereogenic center which was based on the zinc-mediated diastereoselective aza-Reformatsky reaction of isatin-derived chiral N-sulfinyl ketimines 34a–m [30]. The Reformatsky reagent was in situ generated from ethyl bromoacetate (9b

• quaternary stereocenter in uniformly excellent yields (87–99%) and enantioselectivities (96–99% ee). To explain these results, the authors have proposed the catalytic cycle depicted in Scheme 26 in which ligand 65 was deprotonated by ZnMe2 to generate complex L in equilibrium with dimeric complex M. Then

Fluorogenic PNA probes

• Tirayut Vilaivan

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

• quaternary ammonium side chains (Figure 15A). Being electrostatically neutral, PNA cannot bind to these positively charged CCP unless it is first hybridized with DNA to form a negatively charged PNA–DNA complex. The CCP acts as a light harvesting antenna that transfers the energy to another label on the PNA

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• -catalyzed trifluoromethylation of N-aryl acrylamides using Langlois’ reagent (CF3SO2Na) as a trifluoromethyl source and water as the reaction medium (Scheme 36). A variety of CF3-containing oxindoles bearing a quaternary carbon center were formed under this conditions. Furthermore, more CF3SO2Na (3.0 equiv

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• moiety of 5 is resistant to hydrogenolysis, whereas the benzyl ether is readily removed. This order of reactivity is known from previous work [22]. Since it is further known that quaternary benzylammonium compounds undergo hydrogenolysis easier than the corresponding tertiary benzylamines [22], we

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• -condensation of the resulting quaternary products. Carrying out the reaction in bulk without solvents allows scale-up of the quaternary salt synthesis and prevents possible environmental pollution. The known synthetic procedure [50][51] for the target dyes (Scheme 3) was modified to obtain the model compound

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• analogue of streptopyrrolidine was accomplished in 65% overall yield. Keywords: azlactones; dimerization; diasteoreselective synthesis; kinetics; streptopyrrolidine analogue; Findings Azlactones have been acknowledged as a common nucleophilic reagent to introduce a quaternary carbon stereocenter in the α

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• tertiary and quaternary structures. To have a good amide bond isostere, these different aspects should be reproduced, which is mostly the case with the monofluoroalkene moiety [8]. The monofluoroalkene is a rigid molecule as it possesses a double bond. Furthermore, the fluorine atom bears a partial

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• methine groups, as well as three quaternary carbons (Table 1). Only a single carbon (C-19) was sp2-hybridized; its resonance at δ 212.2 ppm indicated the presence of a ketone group. It was hence concluded that the structure of 1 must comprise two ring structures in order to comply with the required

• one occurred with a quaternary carbon (C-12). It was hence evident that the methyl group is attached to the hydroxy-substituted C-12, which itself is further connected with C-11 and C-14. HMBC interactions from H-15a and H-15b to C-12 lend additional support for the placement of the latter. The

• singlets in the 1H NMR spectrum. They were positioned next to the quaternary carbon C-2 on the basis of HMBC interactions. Interpretation of 2D NMR data allowed an extension of this residue with CH-4 and CH2-5. Ultimately, a heteronuclear long-range correlation from H-4 to C-6 linked the two fragments to

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• or L-(tert-butyl)threonine methyl esters, ureido derivatives 38 and 39 were isolated in high yields (96 and 97%, respectively; Scheme 16a,b). A number of other α-amino methyl esters, quaternary amino methyl esters or β-amino methyl esters were also successfully converted to intermediate ureas

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• tolerated. Alkylketone substrates were also successfully converted to 2-oxazolines. Installation of substituents on the tether led to facile formation of product 6m containing a quaternary carbon and compounds 6n and 6o but without any observed diastereoselectivity. Interestingly, the selectivity for 6o

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

• industrial applications [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Different catalytically active structural motives have been used for this purpose so far, and amongst them chiral quaternary ammonium salts have become the most privileged class of chiral PTCs [9][10][11][12][13][14][15

• ][16][17][18][19][20]. Following the pioneering reports of Wynberg et al. [25] and Merck scientists [26] who employed cinchona alkaloid-derived quaternary ammonium salts for asymmetric epoxidations [25] and the α-methylation of a phenylindanone derivative [26] in the late 1970s, early 1980s already

• last millennium then witnessed an increasing interest in the design of new chiral ammonium salt phase-transfer catalysts, with remarkable contributions especially by Maruoka’s group, who developed very efficient and highly versatile chiral binaphthyl-based quaternary ammonium salt catalysts [12][13][14

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• hexahydropyrrolo[1,2-b]isoquinolone derivatives fused with benzene 10 that have pronounced three-dimensional features and potentially contain several quaternary carbon centers (Figure 2). The first aspect has been recently recognized [29] as a central principle in drug design ensuring effective interaction of

• small molecules with protein targets and lower off-target effects. The presence of quaternary carbons is characteristic of the natural products domain and is also gaining prominence in medicinal chemistry [30]. Herein, we disclose the results obtained and observations made in the course of our attempt

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

• , which showed an important four-bonded interaction between the hydrogen of the methylene C(3)=CH- group and the quaternary carbon C(4a) (Figure 2). The carbon C(4a) was interconnected in the HMBC with 2 other three-bonded interactions with hydrogen H-C(8) and H-C(6), whereas for the 16d (SYN) isomer the

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• addition, the electrophilicity of the reacting carbon center of nitrovinylacetamide is likely enhanced by H-bonding, thereby enabling the Michael addition to construct a unique quaternary stereogenic center complex A which would cyclize concurrently via Henry reaction to give the product 3 and regenerates

• stereocenters and a unique quaternary stereogenic center, with good yields, and excellent diastereoselectivity and enantioselectivity using thiourea-catalyzed Michael–Henry cascade reactions. We anticipate that this reaction will simplify the synthesis of complex spirooxindoles containing multiple chiral

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• ) equipped with a Shimadzu LC-6AD pump and a Shimadzu RID-10A refractive index detector. UPLC analysis was performed on an Acquity H-Class UPLC system consisting of a quaternary solvent delivery system, an auto-sampler, and a DAD detector. For column chromatography, silica gel 60 (100–200 mesh, Qingdao

Use of costic acid, a natural extract from Dittrichia viscosa, for the control of Varroa destructor, a parasite of the European honey bee

• Kalliopi Sofou,
• Demosthenis Isaakidis,
• Apostolos Spyros,
• Anita Büttner,
• Athanassios Giannis and
• Haralambos E. Katerinopoulos

Beilstein J. Org. Chem. 2017, 13, 952–959, doi:10.3762/bjoc.13.96

• showed the presence of four quaternary carbons at 36.04 (C-10), 145.44 (C-11), 150.73 (C-4), and 172.83 (C-12) ppm. The tertiary carbons appear at 50.00 (C-5) and 39.48 (C-7) ppm as shown by a DEPT 135° experiment, and the eight secondary carbons appear at 23.58 (C-2), 27.44 (C-8), 30.12 ppm (C-6), 36.96

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• target the primary structure of the terpene synthases or indirectly aim to alter or optimize the product spectrum by changing the tertiary or quaternary structure, respectively [23]. The following paragraphs should give an overview of selected current developments in the areas of mutational engineering

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• broad singlet. The double bond proton in 12c resonating at 6.94 ppm as a singlet shows strong correlation in the HMBC spectrum with the quaternary carbon atoms resonating at 132.3, 130.8, and 123.1 as well as with the tertiary carbon atoms (=CH) at 118.6 ppm (Figure 4). This information clearly shows

• that the double bond (CH=C) is located between the pyrrole nitrogen atom and the benzene ring (Figure 4). On the other hand, the methylene protons in 13c resonating at 4.26 ppm as a singlet shows strong correlation with the quaternary carbon atoms resonating at 137.2 and 135.2 as well as with the

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• , France Laboratoire CEISAM, UMR 6230, University of Nantes, 2 rue de la Houssinière, Nantes, France 10.3762/bjoc.13.74 Abstract An efficient synthetic pathway leading to two carbonated analogues of ribavirin is described. The key-steps in the synthesis of these ribosyltriazoles bearing a quaternary

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• group (δC 211.3 , C-2). The 13C NMR spectrum of compound 5 contained a total of 21 resonances attributable to 5 methyl, 6 methylene, 5 methine and 5 quaternary carbons as indicated by a DEPT 135 experiment. Six characteristic shifts in the 13C NMR spectrum at δC 130.5 (C-4) and 142.8 (C-5), 121.6 (C-7

• correlations for assembling the complete structure were from H3-20 to C-11, C-12 and C-13 connecting fragments A and C. The fragments B and C were then connected according to HMBC cross peaks of the methyl group resonance H3-19 with quaternary C-8 and with C-7 and C-9 (see Figure 6). The absence of a further

• 1H,1H spin system required heteronuclear long range correlations for the elucidation of the remaining structural features and the closure of the cembrane ring. Methylene group CH2-3 exhibited HMBC correlations with resonances of the keto at C-2, sp2 quaternary carbon C-4 and tertiary carbon C-5 and

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• quaternary center with high diastereoselectivity as a consequence of the Stetter–Aldol–Aldol (SAA) reaction sequence. The Stetter–Aldol–Aldol conversion of the phthaldialdehyde derivatives 75 and o-formyl substituted chalcones 76 using the thiazole based carbene 78 as a precatalyst allowed to obtain spiro

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• , and is ideally suited for use in flow applications. Modern HPLC systems are typically equipped with a binary or quaternary pumping system (flow rates ≈0.01–10 mL/min), thermostatted heated compartments (temperatures ≈20–100 °C), multiport sampling valves, as well as separation, purification and UV–vis

Stabilization of nanosized titanium dioxide by cyclodextrin polymers and its photocatalytic effect on the degradation of wastewater pollutants

• Tamás Zoltán Agócs,
• István Puskás,
• Erzsébet Varga,
• Mónika Molnár and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2016, 12, 2873–2882, doi:10.3762/bjoc.12.286

• -M/P) and quaternary ammonium β-cyclodextrin polymer (QABCD-P) in a concentration of 1% (50 mg/5 mL). The polymers were prepared by crosslinking the proper monomers with epichlorohydrin and contained 4–200 β-CD units. None of the monomers could hinder the aggregation of nanoTiO2 in 0.1% NaCl solution

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• substrates, and chiral products were obtained in good yields and selectivities. Remarkably, the performance of tetrakistriazoles was found to be comparable (or in some cases superior) to the well-established thiourea- and squaramide-based catalysts developed for similar transformations. Quaternary

• tetraalkylammonium and alkylpyridinium salts as C–H hydrogen bond donors While quaternary ammonium salts have extensively been used as phase transfer catalysts to activate ionic nucleophiles, recent studies suggest that these compounds can also serve as effective hydrogen bond donors. In 1993 Reetz and co-workers

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• protein across the whole molecule. It describes the interactions between the different elements of the secondary structure. Finally, the assembly of several protein subunits to form a functional complex is described by the quaternary structure [54]. As some amino acids have hydrophobic side chains (e.g