The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• ether cleavage. Aluminium- and borohydrides and the use of sodium hydride Reduction of α-aminonitriles Bifunctional α-aminonitriles exhibit several modes of reactivity. Recent reviews demonstrated the richness of this chemistry and emphasized synthetic applications particularly in heterocyclic chemistry

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• benzoylated thioglycosides with high chemoselectivity and was therefore used in a range of high yielding oligosaccharide syntheses [38]. The bifunctional silicon protective group DTBS (Figure 1) has been used both to increase and decrease the reactivity of glycosyl donors. The 4,6-O-DTBS-protected

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• performed first, in order to avoid undesired transesterification reactions (of the Passerini product) due to the acidic conditions of the Biginelli reaction [33]. A general challenge, which has to be faced in this context, is the choice of solvent and the selection of bifunctional components (which can

• products, however, are in most cases very poorly soluble in non-polar solvents. In our investigations, a solvent mixture of dichloromethane with a small amount of dimethyl sulfoxide (polar but aprotic) allowed the successful combination of both chemistries. All possible bifunctional components for the

• Biginelli–Passerini reaction are represented in Figure 1. Compared to the above mentioned multicomponent tandem approaches, our strategy provides higher yields and makes use of more bifunctional linker components. Careful evaluation of the bifunctional components allowed a pre-selection: A3, B3 and C3 in

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• of phenolic lipids, we have synthesized novel derivatives of phenolic lipids from undecenoic acid where the phenolic acids were linked to the olefinic group of undecenoic acid via a thioamide spacer. Among the various fatty acids reported, 10-undecenoic acid is unique due to its bifunctional nature

Green chemistry

• Luigi Vaccaro

Beilstein J. Org. Chem. 2016, 12, 2763–2765, doi:10.3762/bjoc.12.273

• , including “Strategies in asymmetric catalysis” by Tehshik P. Yoon [6], “Organometallic chemistry” by Bernd F. Straub and Lutz H. Gade [7], “C–H functionalization/activation in organic synthesis” by Richmond Sarpong [8], “Bifunctional catalysis” by Darren J. Dixon [9], “Sustainable catalysis” by Nicholas J

Isosorbide and dimethyl carbonate: a green match

• Fabio Aricò and
• Pietro Tundo

Beilstein J. Org. Chem. 2016, 12, 2256–2266, doi:10.3762/bjoc.12.218

• glucose by hydrolysis. Hydrogenation of glucose to D-sorbitol. An appropriate catalyst for this process should provide both acid sites (hydrolysis) and metallic sites (hydrogenation). Thus, several bifunctional catalytic systems have been investigated [40][41][42][43][44]. The use of ionic liquids as

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• ][14]. Ammonium betaines are defined as intramolecular ion-pairing quaternary ammonium salts. In 2008, we employed this structurally distinct molecular scaffold for designing a novel bifunctional organic base catalyst [23], namely axially chiral ammonium betaines of type 1 (Figure 1) [24][25], and

Cross-linked cyclodextrin-based material for treatment of metals and organic substances present in industrial discharge waters

• Élise Euvrard,
• Nadia Morin-Crini,
• Coline Druart,
• Justine Bugnet,
• Bernard Martel,
• Cesare Cosentino,
• Virginie Moutarlier and
• Grégorio Crini

Beilstein J. Org. Chem. 2016, 12, 1826–1838, doi:10.3762/bjoc.12.172

• distinct commercial materials. To our knowledge, materials able to combine the two functions are rare. Recently, bifunctional natural derivatives have been proposed for this purpose. For example, Zhao et al. [3] proposed a new cyclodextrin-based material for the simultaneous adsorption of metals and

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• isatins has been achieved. This method affords practical and efficient access to chiral 3-amino-3-phosphonyl-substituted oxindole derivatives in high yields with excellent enantioselectivities (up to 99% ee). Keywords: 3-amino-3-phosphonyl-substituted oxindole; α-aminophosphonates; bifunctional

• phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified bifunctional organocatalysts (Figure 1). Results and Discussion To determine suitable reaction conditions for the organocatalytic enantioselective addition reaction of diphenyl phosphonate to ketimines derived from isatins, we

• initially investigated a reaction system with ketimine 1a derived from N-allylisatin and diphenyl phosphonate (2) with organocatalyst in the presence of 4 Å molecular sieves. We first surveyed the effect of the structure of bifunctional organocatalysts I–VI (Figure 1) on enantioselectivity in ethyl acetate

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• domains. Within a module, PS domains are usually located adjacent to DH domains and act on their transiently formed dehydration product [14]. The arrangement is somewhat different in the case of AmbDH3 from ambruticin biosynthesis (Scheme 4) [15]. This bifunctional domain catalyses both steps, dehydration

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• bifunctional molecules substituted by amines, thiols, carboxylates, sulfonates, phosphonates or bisphosphonates [5][6][7]. Particularly, a strong interaction between the NPs and the phosphonic moiety was observed and more interestingly the best results were obtained with bisphosphonate products [8][9]. For the

• past years, our group has focused its interest in the synthesis of various functionalized hydroxymethylene bisphosphonates (HMBPs) [10] and their applications in health science, especially in antitumor therapy [11][12][13]. Herein, we described the synthesis of novel bifunctional PEG-HMBP compounds in

• obtain the expected HMBP-PEG-COOH 23 in 85% yield. Conclusion In summary, novel bifunctional PEG-HMBPs ligands for the coating of iron oxide nanoparticles have been synthesized. The procedure is efficient to introduce different functional groups such as azide, carboxylic acid, amine permitting further

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple

• for the synthesis of MGB-fluorophore and MGB-TFO conjugates via CuAAC (Figure 2). Properties of the conjugates obtained are discussed. Results and Discussion Synthesis of bifunctional linkers Two components in MGB-TFO conjugates must be connected by a linker, which is at least 12 chemical bonds long

• [10][11][34]. Several different bifunctional linkers were designed and synthesized (Figure 3). All of them contain, on one side, an alkyne or azide group for "click chemistry” and, on the other side, either an amino group for interaction with electrophiles (for example, activated terminal phosphates

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

• cyclisation reactions are catalysed by bifunctional lanthionine synthetases for classes II–IV [47][49][54]. Furthermore, dehydration in each of these classes has been shown to proceed via phosphorylation of the amino acid side chain rather than by glutamylation [54]. Class II synthetases (“LanM”) have an N

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• reported the enantioselective conjugate addition of thiols to unactivated α-substituted acrylates followed by enantioselective protonation (Scheme 9) [28]. To overcome the low inherent electrophilicity of 38, the authors postulated that bifunctional iminophosphoran (BIMP) organocatalysts with increased

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• pronucleophile to a substituted furanyl nitroolefin catalysed by a bifunctional cinchonine-derived thiourea has been used as the key stereocontrolling step in a new synthetic strategy to the heavily functionalised piperidine core of keramaphidin B. Keywords: bifunctional organocatalyst; enantioselective Michael

• 1 as a suitable synthetic target. Our plan was to design and implement a new synthetic route that integrated some of our newly developed bifunctional organocatalytic reactions, as well as cascade technologies, to rapidly and stereoselectively build up the core of this fascinating molecule. Herein we

• nitroolefin 9 under the control of a cinchona-derived bifunctional Brønsted base/H-bond donor organocatalyst developed in our group and others [16][17][18][19]. Bifunctional organocatalysed Michael addition studies In our previous total syntheses of nakadomarin A [5][7][20] and manzamine A [10] the

Bifunctional catalysis

• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1079–1080, doi:10.3762/bjoc.12.102

• Darren J. Dixon Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK, Tel: +44 (0)1865 275648; Fax: +44 (0)1865 285002 10.3762/bjoc.12.102 Keywords: bifunctional catalysis; Bifunctional catalysis concerns the use of low molecular weight, structurally defined

• , stereochemically defined products through the action of the bifunctional catalyst system. Many bifunctional catalysts possess either Lewis or Brønsted basic functionality and a hydrogen-bond donor group suitably positioned over a chiral scaffold. Compared to single functional group catalysts, the cooperative

• reactivity and selectivity in synthetically relevant reactions. Furthermore, owing to the great number of pronucleophiles and electrophiles that are available, the number of polar addition reactions that are amenable to catalysis through the action of bifunctional catalysts is enormous, and consequently, the

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• state for the observed stereoselectivity. Pyrrole attacked the ketone from the Si face to generate (R)-3-pyrrolyl-3-hydroxyoxindoles. Very recently, Feng et al. revealed that the bifunctional guanidine (L3)/CuI catalyst can catalyze asymmetric alkynylation of isatins with terminal alkynes, affording

• ). Interestingly, a satisfactory result (89% yield and >99% ee) was also obtained when the reaction was performed on a 7.0 mmol scale using 15% of catalyst loading. Similarly, Chen and co-workers reported that β-ICD, as a bifunctional catalyst, can also efficiently catalyze the MBH reactions of 7-azaisatins with

• of the bifunctional thiourea catalyst (cat. 24, 10 mol %), affording the E-adducts in high yields (up to 95%) and with moderate to good enantioselectivities (up to 99% ee). Different allyl ketones were examined under these conditions, affording the corresponding products in good yields, especially

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

• reactions. Keywords: asymmetric catalysis; bifunctional catalysts; 1H-imidazol-4(5H)-ones; pronucleophiles; thiazol-4(5H)-ones; Introduction Asymmetric catalysis [1][2][3] constitutes a very powerful tool for the preparation of enantiomerically pure compounds [4]. Recent efforts in the field have been

• acceptors in reactions promoted by bifunctional Brønsted bases. 1.2.1 Nitroalkenes as acceptors. Investigation of the base-catalyzed Michael addition reaction of 2-thio-1H-imidazol-4(5H)-ones 4 to nitroalkenes 5 [55] revealed that cinchona alkaloids such as quinine, (DHQ)2Pyr or even thiourea tertiary amine

• an heuristic model (Figure 3) to account for the experimentally encountered selectivity where the catalyst is proposed to act in a bifunctional way. In this proposal the imidazolone would be coordinated to the two NH bonds of the squaramide and the ortho-ArH in C1, whilst the nitroalkene would form a

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• novel amino acid-derived chiral bifunctional organophosphine catalysts, which have successfully applied to catalyze various asymmetric reactions [40][41]. As a general concept, a tertiary phosphine adds to an electrophilic reactant to form a zwitterion which serves as either a nucleophile or a Bronsted

• (diethyl azodicarboxylate, 2a) was selected as the model reaction for the evaluation of chiral phosphine catalysts (Table 1). Using bifunctional thiourea catalysts 4a and 4b, the reaction proceeded smoothly at room temperature to afford the product 3a in good yields, albeit with low enantiomeric excesses

• face of the enolate, driving the electrophile to attack from the Si face. Conclusion In summary, we have realized enantioselective α-aminations of 3-substitued oxindoles with azodicarboxylates by using amino acid-derived bifunctional phosphine catalysts. These reactions afford a variety of chiral 2

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• [22] with 1,4-dithiane-2,5-diol. Based on all above considerations and prompted by our interest in asymmetric synthesis of functionalized tetrahydrothiophenes [14], we wondered whether we could use bifunctional organocatalysts to develop a diastereo- and enantioselective cascade sulfa-Michael

• -dithiane-2,5-diol as precursor of mercaptoacetaldehyde, using 10 mol % loading of different bifunctional organocatalysts (Scheme 1, Table 1). In the case of trans-β-nitrostyrene (1), a mixture of diastereoisomers 5 and 6 were rapidly formed, irrespective of the catalyst used, with a poor level of diastereo

• increased to 50% ee for diastereoisomer 7a when using chlorobenzene as the solvent at room temperature (Table 2, entry 5). It is worth noting that bifunctional organocatalyst VII appears to be more effective in terms of diastereocontrol than previously employed Brønsted base/Lewis acid system TMG/ZnI2

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• bifunctional thioureas on sulfonylpolystyrene resins has been studied in the nitro-Michael addition of different nucleophiles to trans-β-nitrostyrene derivatives. The activity of the catalysts depends on the length of the tether linking the chiral thiourea to the polymer. The best results were obtained with

• the thiourea derived from (L)-valine and 1,6-hexanediamine. The catalysts can be used in only 2 mol % loading, and reused for at least four cycles in neat conditions. The ball milling promoted additions also worked very well. Keywords: bifunctional organocatalysts; organocatalysis; stereoselective

• nitro-Michael addition; supported catalysts; thioureas; Introduction The use of chiral bifunctional thioureas that allow the simultaneous activation of a electrophile, by hydrogen bonding, and a nucleophile, by deprotonation, plays a major role in the stereoselective formation of C–C bonds in different

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

• The 1,2-aminoindanol scaffold has been found to be very efficient, enhancing the enantioselectivity when present in organocatalysts. This may be explained by its ability to induce a bifunctional activation of the substrates involved in the reaction. Thus, it is easy to find hydrogen-bonding

• ; bifunctional; organocatalysis; hydrogen bonding; Introduction The structural and chemical properties of the 1,2-aminoindanol scaffold 1 have transformed aminoindanol derivatives into versatile building blocks for the construction of catalysts and the efficient induction of chirality in asymmetric processes

• disulfides and sulfides, which are involved in the synthesis of ligands and pharmaceutical chiral synthetic precursors [1][2] and in (b) the transfer-hydrogenation reaction catalyzed by bifunctional chiral ruthenium complexes, employed in the synthesis of peptide mimics with an interesting

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• main tools a synthetic chemist has to perform asymmetric catalysis. In this review the synthesis of six-membered rings, that contain multiple chiral centers, either by a ring closing process or by a functionalization reaction on an already existing six-membered ring, utilizing bifunctional (thio)ureas

• involves hydrogen bonding, which is also postulated to be present in enzymatic reactions. (Thio)urea moieties have been employed in order to activate electrophiles and in order to allign them, in a specific manner, so as to react with nucleophiles (Scheme 3) [6][7]. In addition, many bifunctional (thio

• of a bifunctional catalyst. The first family of these bifunctional catalysts, that are going to be discussed, are the "primary amine-thioureas". Initially, catalyst 4 was studied as an organocatalyst in the addition of isobutyraldehyde (1) to (E)-methyl 2-oxo-4-phenylbut-3-enoate (2) for the

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

• developed the pyroglutamic acid-derived triazolium salt 10 which mediated benzoin reactions in similar enantioselectivities [14]. The chiral triazolium catalyst 11 transfers chiral information to the benzoin products by engaging in hydrogen-bonding interactions [15]. Waser’s chiral bifunctional (thio)urea

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• asymmetric organocatalysis. This fascinating class of bifunctional catalyst offers a genuine alternative to the more commonly used thiourea systems and because of the different spacing between the functional groups, can control enantioselectivity where other organocatalysts have failed. In the main, this

• . Keywords: bifunctional; cupreidine; cinchona; cupreine; organocatalysis; Introduction The cinchona alkaloids, comprising quinine (QN), quinidine (QD), cinchonidine (CD), cinchonine (CN, Figure 1), and their derivatives have revolutionized asymmetric catalysis owing to their privileged structures. The

• optimize their stereoselective behaviour has seen their utility burgeon dramatically over the last decade. Of particular note is the use of these cinchona systems within bifunctional thiourea catalysis [3][4][5][6][7][8][9][10][11][12]. Cupreine (CPN) and cupreidine (CPD), the non-natural demethylated