Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• -sulfonylimines proceeded in an unexpected [3 + 2] annulation mode to afford a cyclopentene ring with an all-carbon quaternary center (Scheme 1) [48]. In recent years our group has developed a family of amino acid-derived bifunctional phosphines and has intensively investigated related asymmetric transformations

• [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63]. We became interested in developing an asymmetric variant of the above transformation by utilizing our amino acid-derived bifunctional phosphine catalysts. Results and Discussion We chose the [3 + 2] annulation between α-benzyl-substituted

• allenoate 1a and β,γ-unsaturated N-sulfonylimine 2a as a model reaction and evaluated a number of amino acid based bifunctional phosphines as catalyst. As shown in Table 1, simple L-valine-derived phosphines 3a–c were found to be effective in promoting the reaction, and products were obtained in moderate to

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• in diverse biologically active substances. Here 7-azaisatins turned out to be more efficient electrophiles than the analogous isatins in the enantioselective Morita–Baylis–Hillman (MBH) reactions with maleimides using a bifunctional tertiary amine, β-isocupreidine (β-ICD), as the catalyst. This route

• allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee). Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized. Keywords: 7-azaisatins; β-isocupreidine; bifunctional catalysis; maleimide; MBH

• the identical catalytic conditions [14]. Remarkably, these reactions were usually promoted by bifunctional catalysts, such as β-ICD, whose C6’-OH group served as a H-bond donor to facilitate the proton-transfer step and to stabilize the transition state in MBH reactions [11][12][13][14]. Nevertheless

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• 100049, China 10.3762/bjoc.12.31 Abstract For the first time, a catalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones was achieved with a chiral bifunctional amine-thiourea as a catalyst possessing multiple hydrogen-bond donors. With this developed method, a range of 3-hydroxy-3-nitromethyl-1H

• -pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in acceptable yield (up to 75%) and enantioselectivity (up to 73% ee). Keywords: asymmetric catalysis; bifunctional catalysts; Henry reaction; organocatalysis; 1H-pyrrole-2,3-diones; Introduction Asymmetric organocatalysis has been

• demonstrated to be an effective and versatile strategy in facilitating a variety of organic transformations over the past decade, and numerous catalytic asymmetric reactions have been developed with various activation modes [1][2][3][4][5][6]. In this realm, chiral bifunctional catalysts, possessing two active

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• initial loading protein per gram of Immobead 150 support and the immobilized FDH (FDHI150) showed 31% activity of the free FDH upon immobilization. Another commonly used strategy to covalently immobilize enzyme is using a bifunctional reagent glutaraldehyde. A Schiff base is formed between the carbonyl

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• -substituted hexahydroisoindolinones was developed by using bifunctional tertiary amine-thioureas as powerful catalysts. As far as we know, there is no efficient synthetic method developed toward fully-substituted hexahydroisoindolinones. The products were obtained in good yield and diastereoselectivity. The

• one-pot cascade quadruple protocol features readily available starting materials, simple manipulation, mild conditions and good atom economy. Keywords: bifunctional catalysis; hexahydroisoindolinones; one-pot synthesis; quadruple cascade; Introduction Isoindolines and their congeners are one kind of

• when K2CO3 was used as the catalyst (Table 1, entry 4). When thioureas were used as the catalysts, we also did not get the expected product (Table 1, entries 5 and 6). Since bifunctional tertiary amine-thioureas have been proved as powerful catalysts that can catalyze a variety of organocascade

Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

• Minami Odagi,
• Yoshiharu Yamamoto and
• Kazuo Nagasawa

Beilstein J. Org. Chem. 2016, 12, 198–203, doi:10.3762/bjoc.12.22

• presence of a guanidine–bisurea bifunctional organocatalyst was investigated. The α-amination products were obtained in up to 99% yield with up to 94% ee. Keywords: α-amination; bifunctional catalyst; guanidine; hydrogen-bonding catalyst; urea; Introduction Asymmetric α-amination of β-keto esters is an

• particular, catalytic asymmetric α-amination of β-keto esters has been widely explored, using both metal catalysts and organocatalysts [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. We have developed a series of guanidine–bis(thio)urea bifunctional organocatalysts, and have used them in a variety of

• asymmetric reactions [19][20]. Recently, we disclosed an α-hydroxylation of tetralone-derived β-keto esters 2 using guanidine–bisurea bifunctional organocatalyst 1a in the presence of cumene hydroperoxide (CHP) as an oxidant (Figure 1a) [21]. This reaction provides the corresponding α-hydroxylation products

Versatile deprotonated NHC: C,N-bridged dinuclear iridium and rhodium complexes

• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 117–124, doi:10.3762/bjoc.12.13

• atom. Although most of the studies on NHCs together with metal moieties are based on the interaction of the carbene carbon of the NHC with the metal [23][24][25][26], the high instability due the NH group of the pNHCs can induce secondary interactions leading to bifunctional catalysis [27][28

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• the tricyclic core were controlled via Rh-catalyzed stereoselective C–H insertion and the subsequent reduction from the convex face. Keywords: bifunctional catalysis; hydrogen bonding; organocatalyst; oxa-Michael; prostacyclin; Introduction Prostacyclin (PGI2, Figure 1) is a physiologically active

• nucleophile and relatively unreactive Michael acceptors [27][28][29][30][31][32][33]. We envisioned that our recently developed powerful hydrogen bond (HB)-donor bifunctional organocatalyst [33] could promote the desired reaction of 7 or 8, which can be synthesized from commercial sources 9 or 10. Overall

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• Salerno, Via Giovanni Paolo II, 132, 84084-Fisciano, SA, Italy Institute of Organic Chemistry, Johannes Kepler University Linz Altenbergerstraße 69, 4040 Linz, Austria Dipartimento di Medicina Sperimentale, Università di Napoli, Napoli, Italy 10.3762/bjoc.11.279 Abstract New bifunctional chiral ammonium

• cascade reaction, investigating novel trans-1,2-cyclohexane diamine-based bifunctional ammonium salts 8. These catalysts were recently introduced by our groups in a variety of different reactions [27][28][29], as exemplified by a related aldol-initiated cascade reaction of glycine Schiff base with 2

• already discussed [21][22][23], the bifunctional nature of organocatalysts plays an important role in this reaction to attain satisfactory levels of enantioselectivity. The presence of additional hydrogen donors such as urea groups positively affected the enantioselectivity both in the presence of chiral

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• nitroalkenes has been studied in the presence of two bifunctional catalysts both containing the same absolute chirality at the carbon backbone. The reaction performed in similar conditions allows us to control the syn or anti selectivity of the Michael adduct obtaining good yields and high enantiocontrol in

• of bifunctional tertiary amine/squaramide catalysts [28][29][30][31][32] and, interestingly, we found that catalysts containing the same backbone chirality provided different diastereoisomers, thus allowing the development of a diastereodivergent process. In this report, we wish to present the

• facial stereoselection of those versions in which two stereocentres are generated in the reaction become of special utility to synthetic chemists. In this case, using two different bifunctional tertiary amine/squaramide organocatalysts [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52

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

• (OAc)2) could catalyze the Huisgen alkyne-azide cycloaddition reactions without the addition of the reducing agents and could be produced in high yield when the substrate contains the chelating azide group [67]. Then they synthesized the bifunctional compounds with chelating azide groups and

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• sesterfisherol (59, Scheme 10), the product of a bifunctional sesterterpene cyclase (C25) from Neosartorya fischeri [69]. In this case, [1-13C,2H3]acetate was fed and the resulting labeling pattern of an epoxidation product was analyzed by 13C NMR, revealing a loss of deuterium from carbons C-2, C-6 and C-10 by

• signals mentioned above. To investigate the 1,5-hydride shift, (8,8-2H2)GGPP and IPP were used for an in vitro reaction with the recombinant terpene synthase, utilizing the bifunctional character of the enzyme to form (12,12-2H2)GFPP and its subsequent cyclization to (2H2)-59. NMR data of the obtained

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• 10 is fed to central metabolism while the other is used in a subsequent cycle. As seen in Scheme 4, acetyl-CoA (10) is carboxylated by a bifunctional acetyl-CoA/propionyl-CoA carboxylase to malonyl-CoA (15) with HCO3− and hydrolysis of ATP. The malonate 15 is reduced to 3-hydroxypropionate (16), in

• two steps catalysed by NAD(P)H dependent dehydrogenases. Later in the pathway, propionyl-CoA (17) is the substrate for a second carboxylation with HCO3− to methylmalonyl-CoA (18), performed by the same ATP-dependent bifunctional carboxylase that carries out the first step [71][72]. Succinyl-CoA (5) is

• increased rates of carbon fixation under higher CO2 partial pressures [93][94]. Acyl-CoA carboxylases Though acetyl-CoA carboxylases are widely distributed in living organisms, the existence of bifunctional variants with a role in autotrophy has attracted further interest for their biotechnological

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• performances (Table 1, entries 7 and 8). Similarly, the cross metathesis of 1 with acrylonitrile was conducted to furnish the bifunctional derivative 3 in 71% yield as a mixture of stereoisomers. In that case, high conversions and yields could only be obtained by means of slow addition of the catalyst and high

Robust bifunctional aluminium–salen catalysts for the preparation of cyclic carbonates from carbon dioxide and epoxides

• Yuri A. Rulev,
• Zalina Gugkaeva,
• Victor I. Maleev,
• Michael North and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2015, 11, 1614–1623, doi:10.3762/bjoc.11.176

• efficient for polycarbonate production [12]. Further modification of the salen moiety by the introduction of basic or ammonium salts through alkyl spacers attached to the salen aromatic rings led to the formation of a family of bifunctional catalysts possessing both Lewis acid and nucleophilic catalysis

• of these catalysts was also greatly improved by the introduction of bifunctional versions of the catalyst system, combining an electrophilic aluminium centre with an ammonium cation/nucleophilic-counteranion combination within the framework of a single catalytic species as reported by North [15], Liu

• and Darensbourg [14], and Lu [16] (Figure 1). Unfortunately, the bifunctional derivatives with an alkyl spacer are not very stable at higher temperatures because of the well-known ammonium salt decomposition pathways including: Zaitsev and Hoffman type eliminations [17][18][19] and retro-Menschutkin

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• rupture. Results and Discussion Regarding the synthesis, pyridine nanorod 3, which was also precursor for the synthesis of complex 2a [27], was hydrogenated to receive intermediate 4 (Scheme 1). Subsequent coupling with bifunctional poly(ethylene glycol) (PEG) and purification by dialysis gave compound 5

• bifunctional PEG as written above. Figure 1 shows the expected coordination complexes of our mono- and bivalent model systems with Cu2+ in aqueous solution. In the present work, we analyzed the bivalent systems 2b and 2c by DFS, similarly as for the recently published reference case of 2a [27]. We modified

• , 136.3, 136.8, 147.2, 149.3, 149.7 (7 d, pyr), 157.6 (s, pyr) ppm; IR (ATR) ν: 3305 (OH), 3030–2860 (=C-H, -C-H), 1600–1570 (C=C) cm−1; HRMS (ESI–TOF): m/z [M + H]+ calcd for C16H21N2O, 257.1648, found, 257.1634. Synthesis of pyridine-PEG conjugate 5, ligand of 2b: To a solution of the bifunctional poly

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

• formation of molecular monolayers by chemisorption of bifunctional anchor molecules. This approach depends critically on the choice of a suitable anchor group. Recently, bifunctional catecholates, inspired by mussel-adhesive proteins (MAPs) and bacterial siderophores, have received considerable interest as

• . Keywords: bifunctional anchors; catecholates; multivalency; poly(ethylene glycol); ZnO nanoparticles; Introduction An elegant approach to generate tailored materials and nanoparticles is the formation of molecular monolayers by chemisorption of bifunctional anchor molecules (Figure 1A) [1]. The

• needs to form a stable (in most cases covalent) connection to the target surface. Various bifunctional anchors have been reported for immobilization on different materials and nanoparticles. Basically, silane derivatives are used for glass surfaces [2][3], thiols for noble metal surfaces [4

CO₂ Chemistry

• Thomas E. Müller and
• Walter Leitner

Beilstein J. Org. Chem. 2015, 11, 675–677, doi:10.3762/bjoc.11.76

• fixation of CO2, which can be applied in the synthesis of carboxylic acids [8]. Also highly interesting is the combination of enzymatic and photocatalytic approaches for activating CO2 [9]. Bifunctional catalyst systems are frequently needed and well-understood in the synthesis of cyclic carbonates [10

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• -acylpyrroles [265] (Scheme 39). In their work, diethylzinc and 147 acts as a bifunctional catalyst system where the α,β-unsaturated system is activated through Lewis acid coordination and the catalyst acts as a directing group for the phosphite. Overall the reaction proceeds in both high yield and

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• bifunctional behavior of Cu(OAc)2∙H2O in the reaction sequence. Experimental General procedure for the synthesis of fused triazoloquinoxaline derivatives 4 Substituted phenylpropiolic acids (2) were prepared by the literature procedure [50]. To a mixture of 1-(2-azidophenyl)-1H-benzo[d]imidazole (1a) or 1-(2

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• studies on multicomponent heterocyclizations involving different N-containing polynucleophiles and salicylaldehyde are of particular interest due to the bifunctional reactivity of the latter component. The presence of both electrophilic and nucleophilic reaction centers in salicylaldehyde enables

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• that oligogalactans as long as pentamers can be generated in a single reaction by the activation of a bifunctional galactosyl donor/acceptor in the presence of an initiating alcohol. While isolated yields of the tri-, tetra-, and pentasaccharides are modest, the obtained yields of 19%, 10%, and 4

Synthesis and characterization of a hyper-branched water-soluble β-cyclodextrin polymer

• Francesco Trotta,
• Fabrizio Caldera,
• Roberta Cavalli,
• Andrea Mele,
• Carlo Punta,
• Lucio Melone,
• Franca Castiglione,
• Barbara Rossi,
• Monica Ferro,
• Vincenza Crupi,
• Domenico Majolino,
• Valentina Venuti and
• Dominique Scalarone

Beilstein J. Org. Chem. 2014, 10, 2586–2593, doi:10.3762/bjoc.10.271

• following equation: where f is the number of functional groups in the polyfunctional monomer. For β-CDs, αc is 0.05, meaning that the branching coefficient must be kept lower than 0.05 in order to avoid gelation. In simple systems involving a trifunctional and a bifunctional monomer the branching

• monomer and B the bifunctional one. At the gelation point p = pc and c = cc, which means that gelation can be prevented by stopping the reaction after a short time, when p < pc. However, in the case of complex polyfunctional monomers, such as CDs, the critical branching coefficient differs significantly

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• conventional U-4CR protocol in three-component fashion by the incorporation of bifunctional 2-amino-substituted heterocycles provides an alternative route via an intramolecular N-trapping procedure, leading to various N,N-heterobicyclic systems [5][6][7][8][9][10][11][12]. A number of bifunctional 2