Asymmetric 1,4-bis(ethynyl)bicyclo[2.2.2]octane rotators via monocarbinol functionalization. Ready access to polyrotors

• Cyprien Lemouchi and
• Patrick Batail

Beilstein J. Org. Chem. 2015, 11, 1881–1885, doi:10.3762/bjoc.11.202

• , we have chosen to explore the nucleophilic addition to acetone of the monometallated acetylenide, a reaction that requires a precise control of both the amount of n-BuLi/acetone reactants and temperature. Thus, after chromatographic separation, 1 is readily obtained with excellent purity and good

An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

• Sundaravel Vivek Kumar,
• Shanmugam Muthusubramanian,
• J. Carlos Menéndez and
• Subbu Perumal

Beilstein J. Org. Chem. 2015, 11, 1707–1712, doi:10.3762/bjoc.11.185

• -promoted decomposition of 1,4-dithiane-2,5-diol (2). This would be followed by a formal [3 + 2] annexation via nucleophilic addition of compounds 1 to the carbonyl of intermediate 4 followed by addition of the thiolate anion onto the iminium functionality thus generated to give 5. Subsequent elimination of

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• presence of phosphane catalysts an umpolung addition takes place, whereby the nucleophilic addition occurs inversely at the beta-gamma double bond [22][23]. Vinyl azides have been prepared by hydroazidation of allenyl esters through a Michael-type addition with high regio- and stereoselectivity [24

• ]. Inspired by these results we focused our attention in the present study on the reaction of allenoates with TMSX with the aim to determine the extent by which Selectfluor could influence the electrophilic versus nucleophilic addition manifolds. Results and Discussion The reaction of benzyl allenoate (1

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• unsymmetrical hexahydropyrimidine-fused 1,2- and 1,4-naphthoquinones by the reaction of 4-amino-l,2-naphthoquinone and 2-amino-1,4-naphthoquinone with amines and formaldehyde in moderate yields [37]. Ohta et al. studied the nucleophilic addition reaction of methylamine to 2-bromo-3-hydroxymethyl-1,4

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• undergoes a nucleophilic addition to a forming a dimer radical anion that is reduced to e that is then protonated to the dimer f. In path (III) the radical coupling of two radical anions b leads to the dianion e, which is protonated to the product. We first checked the cathodic reduction of (E)-2-nitro-1

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• ) was further converted by condensation with 2-N-maleimido-ethylamine and N-ethyl-N´-dimethylaminopropylcarbodiimide (EDC) [6]. The monovalent ligand peptide 2 was attached to the dextran carriers by nucleophilic addition of the thiols to the maleimide double bond furnishing peptide–polymer conjugates

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• chloride to give acrylamide 4. Treatment of 4 with dimethylamine and excess KOH leads to the nucleophilic addition of the amine and saponification of the methyl esters in one step to give the free acid 5 after acidic work-up. Subsequent coupling of 5 to dopamine acetonide 6 with EDC and HOBt gave the

• ] were converted to the corresponding triscatecholates 11 and 13 by coupling to dopamine (Scheme 2). The resulting triscatecholates 11 and 13 may be used as synthetically flexible platforms for functionalizations of surfaces via either nucleophilic addition (to the Michael acceptor in 11) or radical

Photocatalytic nucleophilic addition of alcohols to styrenes in Markovnikov and anti-Markovnikov orientation

• Martin Weiser,
• Sergej Hermann,
• Alexander Penner and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2015, 11, 568–575, doi:10.3762/bjoc.11.62

• Martin Weiser Sergej Hermann Alexander Penner Hans-Achim Wagenknecht Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany 10.3762/bjoc.11.62 Abstract The nucleophilic addition of methanol and other alcohols to 1,1-diphenylethylene (1

• -Markovnikov-type addition of cyanide to styrene [18]. Recently, we showed by a library of different chromophores that 1-(N,N-dimethylamino)pyrene (Py) can be applied as photocatalyst for the nucleophilic addition of methanol to styrene derivatives into the Markovnikov orientation [19]. Most recently, Nicewicz

• transfer that recovers the photocatalyst from the PDI radical anion after nucleophilic addition, since addition of Ph–SH as electron and proton shuttle helped to significantly accelerated reactions [20][21]. In this respect, oxidative and reductive mode behaved similarily since both types of photocatalysis

Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines from aziridines

• Hongnan Sun,
• Binbin Huang,
• Run Lin,
• Chao Yang and
• Wujiong Xia

Beilstein J. Org. Chem. 2015, 11, 524–529, doi:10.3762/bjoc.11.59

• mechanism was proposed as shown in Scheme 4. Initially, aziridine 1a might participate in single-electron transfer (SET) with the persulfate anion to render the radical cation A [32][34]. Concerted ring opening and nucleophilic addition leads to amino radical intermediate B, which is converted to the

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• involves the nucleophilic addition of N-hydroxyimides to aldehydes followed by the oxidation of the resulting adduct to form the activated ester. For example, the C–O coupling of aldehydes 153 with N-hydroxyimides 154 was carried out in the presence of the Bu4NHal/t-BuOOH system (Hal = I or Br) [145]. This

• oxidative C–O coupling of alcohols and aldehydes 161–164 with N-hydroxysuccinimide (154a) was performed in the presence of (diacetoxyiodo)benzene [147] or iodoxybenzoic acid (IBX) [148] as the oxidant. The authors hypothesized that the reaction proceeds via the nucleophilic addition of N-hydroxysuccinimide

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• electrophilic. This strong polar effect is the real driving force of the overall process, making the imine more reactive towards nucleophilic addition by the ketyl radicals (Scheme 4, reaction 7), and consequently shifting the equilibrium of reaction 6 towards the right. The catalytic cycle is concluded with

• reported optimized conditions for the selective free radical nucleophilic addition of ethers and alcohols to ketimines generated in situ under non-anhydrous conditions. The protocol consists of a three-component, one-pot reaction involving an aromatic amine, a ketone, and the source of the ketyl radical

• ketimines and promoting their reactivity towards the nucleophilic addition. The general applicability of the reaction has been demonstrated by reacting different aromatic amines, ketones, ethers and alcohols. This approach provides a new protocol for the simple and convenient synthesis of a wide range of

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• ). Vinylogous nucleophilic addition of the enamine to 5a generates 8a. This hypothesis is supported by the reaction of 5a with crotonaldehyde in the presence of a MacMillan-type imidazolidinone catalyst [41] and TFA which delivers 8b. Formation of cyclic products 8b and 9 is rationalised by intramolecular

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• acetylenedicarboxylate results in an active zwitterionic intermediate (A). In the meantime, the condensation of isatin with malononitrile or ethyl cyanoacetate in the presence of triethylamine affords isatylidenemalononitrile or its derivative (B). Then the nucleophilic addition of the zwitterionic intermediate (A) to

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions

• Carolin Fleischmann,
• Hendrik Wöhlk and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2263–2269, doi:10.3762/bjoc.10.235

• (PP-NH2) was obtained through a Michael addition reaction of PP-AAm and cysteamine hydrochloride. The hydrochloride was chosen in order to disable the competing nucleophilic addition of the amine and therefore, to prevent the formation of side products. The purified PP-NH2 was then converted into the

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• annulations of allenoates and activated alkenes, the first C–C bond forms through nucleophilic addition of the β-phosphonium dienolate intermediate to the activated alkene at its α- or γ-carbon atoms. Conversely, when allenoates are mixed with pronucleophiles that contain acidic protons in the presence of a

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

• elementary processes from acetaldehyde to aminonitrile. Bold numbers are defined in Scheme 5. Two transition states (A and B) of the nucleophilic addition of (S)-α-phenylethylamine to acetaldehyde. (H2O)10 is also included, and the molecular formula of the reaction system is C11H36N2O11. Energy changes along

• 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

Aryl substitution of pentacenes

• Andreas R. Waterloo,
• Anna-Chiara Sale,
• Dan Lehnherr,
• Frank Hampel and
• Rik R. Tykwinski

Beilstein J. Org. Chem. 2014, 10, 1692–1705, doi:10.3762/bjoc.10.178

• acetylide to pentacenequinone (Scheme 1) [21][35][36][37][38]. With these two ketones in hand, a second nucleophilic addition was initiated. Thus, commercially available aryl halides dissolved in dry THF were subjected to lithium halogen exchange at −78 °C using n-butyllithium. A substoichiometric amount of

• nucleophilic addition (yields given are for the pentacene product 3, over the two steps from either 4a or 4b). Functionalization of iodoaryl pentacene 3g using the Suzuki–Miyaura cross-coupling reaction. Optical properties of pentacenes 3a–k, unsubstituted pentacene (PEN), and TIPSPc. Thermal properties of a

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• 7) resulted in a decrease of the dr. This may be caused by a minor stereofacial differentiation of the intermediate carboxylate iminium ion during the nucleophilic addition of the isocyanide. Isocyanide 2b (Table 2, entry 3 and entry 4), formally derived from glycine, afforded satisfactory results

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• the farnesyl residue (for atom numbering see Scheme 1), followed by regio- and stereoselective nucleophilic addition of water (and methylation) would deliver heronapyrroles A and B. Similarly, regio- and stereoselective nucleophilic addition of water to a tris-epoxy farnesyl intermediate 4 could

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• is in favor of the first mechanism (Scheme 3-i), since differences of the reaction rate should be expected for the nucleophilic addition of trialkylamine on carbon tetrachloride (Scheme 3-ii) depending on the structure of the alkyl chains. The works of Steinberg eliminated the possibility of a

• expected phosphoramidate was jointly isolated with 5 to 10% of thiophosphoramidate resulting from a cyclization reaction. The chiral phosphoramidates (Scheme 32-ii and iii) were tested as a chiral catalyst for the nucleophilic addition of diethylzinc [107] on benzaldehyde or for the asymmetric borane

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• unit. Representative synthetic reactions of fullerene C60 (2) include cyclopropanation [29][30], [3 + 2] cycloaddition [31][32], [4 + 2] cycloaddition [33], nucleophilic addition [34], and radical addition reactions [35]. Two of the earliest and most widely used reactions, the Bingel–Hirsch reaction

• The Bingel–Hirsch reaction produces 3-membered rings by a reaction that begins with a nucleophilic addition to a fullerene (Scheme 1). It is considered to be one of the most valuable preparative methods for functionalizing fullerenes, since it changes both the solubility and the electrochemical

• used to functionalize the existing polyarenes and/or to extend them to larger PAHs. The most common class of reactions is the electrophilic aromatic substitution; however, free radical, nucleophilic addition, reduction, and oxidation reactions are also possible. To synthesize larger PAHs that are not

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• Lukasz Gorecki Artur Mucha Pawel Kafarski Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland 10.3762/bjoc.10.85 Abstract The Abramov reaction, a base-catalyzed nucleophilic addition of dialkyl H

• we planned to envisage a nucleophilic addition of dialkyl phosphites to quinine-based carbonyl compounds and obtain 1-hydroxyalkylphosphonate derivatives (Abramov reaction, phospha-aldol reaction [22][23]). The scope, stereochemistry and side-reactions of the addition are described. Results and

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• . Results and Discussion Synthesis The synthesis of 1–3 requires the three different 2,2’-bipyridines that carry isothiocyanate functions and a monoaminated β-cyclodextrin that could be coupled with each other via two-fold nucleophilic addition. Symmetrically 4,4’- and 6,6’-disubstituted 2,2’-bipyridines

• furnished 19 [30] which could by peracetylated into 20 [31] using acetic acid anhydride both in decent yields. Staudinger reduction of the azide group of 20 then afforded the desired monoaminated cyclodextrin 21 (Scheme 4). Finally, nucleophilic addition of 21 to the diisothiocyanato-2,2’-bipyridines 14–16

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• proteinogenic and nonproteinogenic α-amino acids were prepared. The synthetic methodology was based on nucleophilic addition of (trifluoromethyl)phosphinic acid or (difluoromethyl)phosphinic acid or its ethyl ester to substrates with C=N or activated C=C double bonds. Analogues of glycine, phenylglycine

• P–H compounds with CF3 or CHF2 groups attached to phosphorus. Three-component one pot Mannich-type reactions of CF3(H)P(O)(OH) with dibenzylamine and aldehydes were investigated. Also nucleophilic addition of CF3(H)P(O)(OH) or CHF2(H)P(O)(OEt) to Shiff bases, aminoacrylates and

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• ][2][3], because the ester group can serve as an activator to enhance the reactivity of the C=N double bond, thus making the following nucleophilic addition easier [4][5]. More attractively, the transformation of α-imino esters can provide an easy access to various natural and unnatural α-amino acid