Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• nucleophile and then as a leaving group in cyanide-catalysed benzoin reactions [8]. Analogously, Breslow invoked the generation of a nucleophilic thiazolylidene species 1 via deprotonation of the thiazolium salt by base. The ylide 1 may also be represented as its resonance structure 1’ (carbene). Nucleophilic

• addition of 1 to aromatic aldehyde generates the tetrahedral intermediate 2. The latter then undergoes a proton shift to furnish an enaminol derivative 3. The aldehyde carbonyl carbon has now transformed into a nucleophilic entity by virtue of conjugation to the nitrogen and sulfur lone pairs. This acyl

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• diazides with substitued alkynes. There are mainly two types of methods for the construction of bistriazoles from diazides: (1) Starting from the substrate-containing good-leaving groups, the diazides could be generated in situ by nucleophilic addition with NaN3, and then the double CuAAC reactions could

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

• in toluene through nucleophilic addition of electron-rich nitriles to the oxacarbenium ion intermediate of 1,2;3,4-di-O-isopropylidene-β-D-psicofuranose derivatives with concomitant intramolecular trapping of the C2 hydroxymethyl group on the electrophilic nitrilium carbon. These carbohydrate-derived

• , the complete consumption of the starting material and the formation of spiro 2-substituted-2-oxazoline 6a in 69% yield was observed. This Ritter-like reaction is known to proceed via TMSOTf-mediated in situ cleavage of the 1,2-O-isopropylidene group, generating an oxacarbenium ion and its nucleophilic

• addition to the nitrile (Scheme 2, 6ab). This occurs with simultaneous intramolecular trapping of the C2 hydroxymethyl group on the electrophilic nitrilium carbon (Scheme 2, 6ac) giving spiro 2-substituted-2-oxazoline 6 (Scheme 2). It is important to note that the 3,4-O-isopropylidene group is unaffected

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• reaction. It has been shown that the priority path of the reaction at the nitrogen atom unsubstituted 2-methylbenzimidazole with o-chloranil includes the nucleophilic addition of the quinone to the NH group [28], whereas the interaction of 3,5-di(tert-butyl)-1,2-benzoquinone with 2-methylbenzimidazole

• of 2-acyl-5,6,7-trichloro-1,3-tropolones under the action of alcohols [17][32] or hydrazines [32] has been previously reported. The suggested primary step of these reactions is a nucleophilic addition to the carbonyl carbon of an acyl group. In our case (compounds 5 and 6), the reaction most probably

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• results in hand, two possible reaction mechanisms were proposed and shown in Scheme 3. 5-Aminopyrazole-4-carbonitrile 6 was obtained from the reaction of hydrazine 1 and methylenemalononitrile 2 through nucleophilic addition, cyclization and aromatization. The nucleophilic attack of the amino group of 6

• undergoes a nucleophilic addition and loses a water molecule to afford the final product 5. All products were characterized by IR, 1H NMR, 13C NMR and HRMS. A final confirmation of the structure of the reaction product 5g was determined by X-ray diffraction (Figure 2) [50]. Conclusion In summary, we have

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• , enaminoketone 16ae, and pyridine 9ae was observed [54][55]. Further heating this mixture of intermediates for 4 h resulted in the sole formation of pyridine 9ae. This experiment suggests that the conversion of nitrone 8ae to pyridine 9ae proceeds by oxygen transfer to give 16ae and nucleophilic addition of the

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• to form a cyclic imine – a highly strained three-membered 2H-azirine, 4. Subsequent attack by the acid results in the aziridine adduct 5, which then undergoes intramolecular nucleophilic addition on the carboxylic group with the nitrogen lone pair, ultimately yielding α-amido-1,3-diketone 3 by ring

• acid and not with other carboxylic acids. A plausible mechanism has been illustrated for the formation of substituted oxazoles (Scheme 6). Initial attack of trifluoroacetic acid on the azide via Michael addition affords active intermediate 9. Subsequently, an intramolecular nucleophilic addition takes

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• Lewis acid, only EtAlCl2 is able to trigger the reaction toward the formation of the desired cycloadducts 3/3'. Similarly, Piersanti and co-workers reported the unique capability of EtAlCl2, with respect to related hard Lewis acids, to activate 2 toward the nucleophilic addition of indoles [29]. They

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• iminyl radicals (Scheme 2). However, the instability of N–H ketimines [50] limits their use as starting materials. Recently, we have studied the chemical reactivity of N–H ketimines towards copper-catalyzed aerobic reaction conditions [51][52][53]. In these studies, we employed the nucleophilic addition

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• and death. This explains why it is down-regulated during carcinogenesis and opens the door for nucleophilic addition of amines to 5,6α-EC as a new lead for developing potential anticancer drugs [15]. Apart from antimicrobial and antiproliferative activities of cholesterol derivatives, other

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