Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• step is the nucleophilic addition of diethyl phosphite to the C=N bond of the imines resulting in phosphonates III or IV, respectively. Then, the elimination of an amine or ethanol and the addition of another unit of diethyl phosphite may lead to (aminomethylene)bisphosphonates (VI). If the amine is in

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

• successfully used trialkyl orthoformates 13 to produce dialkyl (2-oxo-4-(trifluoromethyl)-1,2-dihydropyrimidin-5-yl)phosphonates 14 which were converted to dialkyl (4-alkoxy-2-oxo-4-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidin-5-yl)phosphonates 15 through the nucleophilic addition of the liberated alcohol to

• resulting from the reaction of 2-(2-formylphenyl)ethanones 120 with amines 121. The tandem nucleophilic addition of phosphite to the imine and subsequent condensation of the formed amine with the ketone group leads to 1,2-dihydroisoquinolin-1-ylphosphonates 123. A wide range of substituted aromatic amines

• one-pot reaction of 2-bromobenzaldehydes 169, alkynes 170, amines 171, and diethyl phosphonate under multicatalytic conditions including palladium and copper salts (Scheme 37) [75]. This process presumably involves a sequential Sonogashira coupling/cyclization-nucleophilic addition reaction, which is

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• aminovinylcysteine [62] (AviCys, Figure 5A). This is found in a variety of RiPPs that also feature conventional lanthionine rings, such as epidermin [63] (Figure 5A), mersacidin [64] and cypemycin [65]. In epidermin, a S-[(Z)-2-aminovinyl]-D-cysteine (AviCys) residue is formed by the 1,4-nucleophilic addition of an

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. Keywords: 1,2-addition; aryl iodides; ketones; nucleophilic addition; palladium catalysis; Introduction For our systematic studies on samarium diiodide promoted cyclizations

• tetralin derivatives are in the crude product mixture, but we isolated only compound 16 in pure form in 24% yield. Not surprisingly, the p-methoxy substituent favored the elimination of water from the primary addition product to generate the central double bond of 16. Discussion The nucleophilic addition

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

• steps. Heterocycle 7 is a bench stable white powder that can be stored indefinitely in a dessicator without any noticeable decomposition. The sulfonamide moiety activates sulfur towards nucleophilic addition, making the first addition of an organometallic reagent faster than the second. By performing

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• groups [38][39][40][41][42][43], is based on a sequential nucleophilic addition and an intramolecular allylic substitution reaction. It relies on the coupling of different homoallylic nucleophiles of general type 6 to diverse electrophiles 7 such as Michael acceptors, or heteroolefins as for example

• . Modular concept for manzacidin synthesis based on a Tsuji–Trost coupling of joint intermediate 5. X-ray structure of 39. General concept for heterocycles synthesis based on a nucleophilic addition and Tsuji–Trost coupling. Synthesis of homoallylic alcohol 12 by multi-component reactions. Preparation of

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• central nervous system diseases [30][31][32][33][34]. In the proposed reaction pathway, the nucleophilic addition of the indole derivatives 2 to the nitroalkene 13 progresses in a stereocontrolled manner due to the creation of a ternary complex with the chiral bifunctional thioamide ent-6 (TS4, Scheme 7

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