Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• 10.3762/bjoc.8.132 Abstract The synthesis of diverse substituted indole structures on solid supports is described. The immobilization of nitrobenzoic acid onto Merrifield resin and the subsequent treatment with alkenyl Grignard reagents delivered indole carboxylates bound to solid supports. In contrast to

• purchased from CalBiochem-NovaBiochem. General washing procedure for resins: After reaction the resins are subsequently washed according to the following procedure: (MeOH, THF, n-pentane, CH2Cl2) three times, (MeOH, DMF, n-pentane, THF) once, (n-pentane, CH2Cl2, n-pentane) twice. GP 1 - Immobilization of

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• immobilization of Cinchona organocatalysts using thiol–ene chemistry, in which catalyst immobilization and bead polymerization is combined in a single step. A solution of azo initiator, polyfunctional thiol, polyfunctional alkene and an unmodified Cinchona-derived organocatalyst in a solvent is suspended in

• ; Introduction Polymer-supported chiral organocatalysts have emerged as a rapidly expanding field of research in recent years [1], in part due to the traditionally emphasized advantages of polymeric immobilization (facilitated separation and recovery procedures, recycling etc.), but perhaps even more due to the

• , we have been engaged in the development of scalable and expedient syntheses of polymer-supported organocatalysts for some time now [6][7]. In our bottom-up approach for the preparation of polymer-supported organocatalysts, the catalyst immobilization and the preparation of the polymer scaffold are

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• yields of 78–98% (Table 3). Conclusion Diaryltriazoles were obtained in an efficient three-step solid-phase procedure. Immobilization of aromatic azides on commercial Wang resin followed by copper(I)- or ruthenium(II)-catalyzed 1,3-cycloaddition and subsequent cleavage of the product from the resin gave

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• azides and alkynes (CuAAC) used as the immobilization strategy [44][45][46], led to improved efficiency, both in terms of catalytic activity and asymmetric induction, and different behaviour of the resulting materials in terms of hydrophilicity or hydrophobicity [47][48][49][50]. An even better

• chemistry with solid-supported catalysts allows the advantages inherent to both technologies to be added together. Thus, the physical immobilization of the catalyst in a packed-bed reactor allows it to be submitted constantly to the reaction conditions, avoiding possible degradation of the catalyst during

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• was used for cofactor regeneration, and immobilization of NADH on PEG prevented loss of the cofactor in the continuously operated reactor. Space-time yields of 700 g L−1 day−1 were achieved with the optimized reactor at 95% conversion. Deactivation of enzyme and PEG–NADH led to a decrease of

• achieved without immobilization or addition of charged polymer, but by using nanofiltration membranes instead of ultrafiltration ones [25]. The reactor for the synthesis of L-tert-leucine (11) from trimethylpyruvate (10) catalyzed by leucine dehydrogenase (Scheme 4) was operated for 10 days with a total

• continuous multistep enzymatic synthesis of fine chemicals, where cofactor regeneration is required. In such cases the whole-cell in vivo approach is advantageous over in vitro approaches, because it is not necessary to use immobilization or nanofiltration membranes for the retention of small cofactor

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• of an appropriate immobilization strategy facilitates catalyst isolation and reuse; (iii) the development of highly efficient selective or, when applicable, enantioselective chemical transformations. Although the examples reported in the literature and considered in this review are currently confined

• catalyst, the use of immobilized systems is clearly preferred [10]. Besides, this is often associated with an increase in the long-term stability of the corresponding catalytic system [11]. For this purpose, immobilization was carried out on different supports. The most usual approach involved the

• has increased significantly over the past few years [31]. Different approaches to the immobilization of catalysts in order to design flow processes in scFs can be mentioned: a) Solid heterogeneous catalysts: Hydrogenation processes, in particular those based on solid heterogeneous catalysts derived

Continuous flow hydrogenation using polysilane-supported palladium/alumina hybrid catalysts

• Hidekazu Oyamada,
• Takeshi Naito and
• Shū Kobayashi

Beilstein J. Org. Chem. 2011, 7, 735–739, doi:10.3762/bjoc.7.83

• decreased catalytic activity, are both serious problems with the use of conventional heterogeneous catalysts. To address these problems, we recently developed novel methods for the immobilization of metal and non-metal catalysts on supports. This involved the development of microencapsulated (MC) and

• and substantially increase production. We also recently reported novel transition metal catalysis involving the immobilization of Pd or Pt onto polysilane supports by the microencapsulation method [12]. The Pd catalyst (Pd/PSi) had high activity with no or very little leaching of Pd, and it could be

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• , following immobilization on glass slides, their binding to the lectin DC-SIGN was assessed [31]. Significant questions remain in the area of PIM/LM/LAM biosynthesis that could be assisted by suitable well-defined mannan substructures. For example, the identity of the α-1,2-mannosyltransferase(s) involved in

Synthesis and self-assembly of 1-deoxyglucose derivatives as low molecular weight organogelators

• Guijun Wang,
• Hao Yang,
• Sherwin Cheuk and
• Sherman Coleman

Beilstein J. Org. Chem. 2011, 7, 234–242, doi:10.3762/bjoc.7.31

• into 3-dimensional networks. The resulting gels may find applications as soft materials for drug delivery, enzyme immobilization, scaffolds for tissue engineering, etc. [10][11][12][13][14]. The structures of LMWGs span a diverse range; carbohydrates have frequently been used in the synthesis of LMWGs

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• -component, two-step “catch and release” solid-phase synthesis of 3,4,5-trisubstituted pyrazoles was reported which involved a base-promoted condensation of a 2-sulfonyl- or a 2-carbonyl-acetonitrile derivative (29 or 33) with an isothiocyanate and in situ immobilization of the resulting thiolate anion (30

Hoveyda–Grubbs type metathesis catalyst immobilized on mesoporous molecular sieves MCM-41 and SBA-15

• Hynek Balcar,
• Tushar Shinde,
• Naděžda Žilková and
• Zdeněk Bastl

Beilstein J. Org. Chem. 2011, 7, 22–28, doi:10.3762/bjoc.7.4

• : alkene metathesis; catalyst immobilization; hybrid catalysts; mesoporous molecular sieves; Ru–alkylidene complexes; Introduction Ru–alkylidene complexes (Grubbs and Hoveyda–Grubbs catalysts, 1 and 2, respectively, Figure 1) belong to the most active and frequently used metathesis catalysts. These

• catalysts are important tools in organic synthesis due to their high tolerance of heteroatoms in substrate molecules. Immobilization of these complexes on solid supports has attracted attention, because it opens the possibility for easy catalyst–product separation and catalyst reuse. The production of

• products free from catalyst residues is especially important in the synthesis of drugs and some other fine chemicals. Several strategies have been developed for the immobilization of Grubbs and Hoveyda–Grubbs catalysts on solid supports [1][2][3][4][5][6]. Generally, the complex can be attached to the

Expanding the gelation properties of valine-based 3,5-diaminobenzoate organogelators with N-alkylurea functionalities

• Hak-Fun Chow and
• Chin-Ho Cheng

Beilstein J. Org. Chem. 2010, 6, 1015–1021, doi:10.3762/bjoc.6.114

• immobilization of solvent molecules. These molecules possess many potential applications in biomedical science, environmental and separation technology [1][2][3][4][5][6]. One key problem in the design and synthesis of organogelators lies in the difficulty in predicting their gelation properties beforehand. Most

Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical effects

• Janja Makarević,
• Milan Jokić,
• Leo Frkanec,
• Vesna Čaplar,
• Nataša Šijaković Vujičić and
• Mladen Žinić

Beilstein J. Org. Chem. 2010, 6, 945–959, doi:10.3762/bjoc.6.106

• entrapped by capillary forces, the formation of a dense network composed of thin fibers should possess smaller compartments and hence a higher solvent immobilization capacity compared to those less dense formed by thick fibers. The TEM observed thicknesses of gel aggregates existing in water/DMSO and

• aggregation. The TEM investigations have shown that in the highly lipophilic solvents the extensive intermolecular hydrogen bonding may lead to the formation of wide and relatively short tapes giving a gel network of low solvent immobilization capacity. Molecular modeling studies revealed that the homochiral

Pyridinium based amphiphilic hydrogelators as potential antibacterial agents

• Sayanti Brahmachari,
• Sisir Debnath,
• Sounak Dutta and
• Prasanta Kumar Das

Beilstein J. Org. Chem. 2010, 6, 859–868, doi:10.3762/bjoc.6.101

• the immobilization of solvents. Low-molecular-weight-gelators (LMWG) have received more attention than their polymeric analogues for a number of scientific applications due to their thermo-reversible nature and their prompt response to external stimuli [19]. A critical balance between hydrophilic and

Organic gelators and hydrogelators

• Jean-Pierre Desvergne

Beilstein J. Org. Chem. 2010, 6, 846–847, doi:10.3762/bjoc.6.99

• liquid) which behaves as a visco-elastic material (soft matter) due to the immobilization of solvent molecules in a three-dimensional network. This network results from the self-assembly of the gelling agent into fibres via non-covalent interactions such as hydrogen bonding, π–π stacking, van der Waals

Hybrid biofunctional nanostructures as stimuli-responsive catalytic systems

• Gernot U. Marten,
• Thorsten Gelbrich and
• Annette M. Schmidt

Beilstein J. Org. Chem. 2010, 6, 922–931, doi:10.3762/bjoc.6.98

• the immobilization of amino functional targets are obtained in a single polymerization step by grafting-from copolymerization of an active ester monomer from superparamagnetic cores. The comonomer, oligo(ethylene glycol) methyl ether methacrylate, has excellent water solubility at room temperature

• , biocompatibility, and a tunable lower critical solution temperature (LCST) in water. The phase separation can alternatively be initiated by magnetic heating caused by magnetic losses in ac magnetic fields. The immobilization of porcine pancreas trypsin to the core–shell nanoparticles results in highly active

• nanoparticles; immobilization matrix; thermoflocculation; Introduction The use of an external stimulus for the activation of (bio)chemical reaction processes can be a valuable tool in fundamental research and in applications such as reaction kits or lab-on-a-chip systems, as it allows for on-demand triggering

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• pyrrolidone) as the starting copolymer. Poly(NVP) is known to be biocompatible and to promote adhesion. NVP-based maleic copolymers have been reported for BSA immobilization [14] as well as for the preparation of polymer nanoparticles [10][15]. The choice of the carbohydrate moieties to be grafted onto the

Ring opening metathesis polymerization-derived block copolymers bearing chelating ligands: synthesis, metal immobilization and use in hydroformylation under micellar conditions

• Gajanan M. Pawar,
• Jochen Weckesser,
• Siegfried Blechert and
• Michael R. Buchmeiser

Beilstein J. Org. Chem. 2010, 6, No. 28, doi:10.3762/bjoc.6.28

• N,N-dipyrid-2-ylacetamide and their use in hydroformylation reactions [9]. Here, we report on the immobilization of a Rh-N,N-dipyrid-2-ylacetamide-based catalyst on a soluble, amphiphilic, ring-opening metathesis polymerization- (ROMP) derived block copolymer and its use in hydroformylation [10

Convergent syntheses of Le^X analogues

• An Wang,
• Jenifer Hendel and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2010, 6, No. 17, doi:10.3762/bjoc.6.17

• competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N-acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40 °C under excess of BF3·OEt2 activation and proceeded best if the acceptor

• three Lex derivatives 1–3 (Figure 1) from one common protected trisaccharide intermediate. These three Lex analogues (1–3) will be used respectively for competitive binding experiments (1), conjugation to carrier proteins (2) and immobilization to a gold plate (3). Results and Discussion Our synthetic

• as those reported by de la Fuente and Penadés for a similar analogue [33]. Following published procedures, the disulfide dimer 3 will be reduced immediately prior to its conjugation to proteins [53] or immobilization on gold surface or gold nanoparticules [34]. In conclusion, we have reported above

Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

• Julien Rolland,
• Xacobe C. Cambeiro,
• Carles Rodríguez-Escrich and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2009, 5, No. 56, doi:10.3762/bjoc.5.56

• ], methylation [17], and arylation [18] of a wide family of substrates at low catalyst loadings. In recent times, we have developed strategies for the immobilization of analogues of 1 onto solid supports [19][20][21][22]. Among the ligands resulting from these studies, the polystyrene-supported catalyst 2

Synthesis of novel photochromic pyrans via palladium- mediated reactions

• Christoph Böttcher,
• Gehad Zeyat,
• Saleh A. Ahmed,
• Elisabeth Irran,
• Thorben Cordes,
• Cord Elsner,
• Wolfgang Zinth and
• Karola Rueck-Braun

Beilstein J. Org. Chem. 2009, 5, No. 25, doi:10.3762/bjoc.5.25

• the presence of an Fmoc protecting group for the direct synthesis of ω-amino acid 6. Also, a Sonogashira reaction was conducted towards the synthesis of naphthopyran precursor 4, which is suitable for attachment to tripodal linker systems for the immobilization on surfaces [26]. Results and Discussion

Polyionic polymers – heterogeneous media for metal nanoparticles as catalyst in Suzuki–Miyaura and Heck–Mizoroki reactions under flow conditions

• Klaas Mennecke and
• Andreas Kirschning

Beilstein J. Org. Chem. 2009, 5, No. 21, doi:10.3762/bjoc.5.21

• heterogenization of transition metals. A major hurdle for industrial applications of heterogenized homogeneous metal catalyst is associated with keeping metal leaching down to a minimum. Immobilization can be regarded as one enabling technique in organic chemistry [5][6] that in conjunction with continuous flow

• processes creates an ideal setup for an automated solution-phase synthesis. Furthermore, this combination of enabling techniques has great potential in the production of fine chemicals [7][8]. In continuation of our efforts in developing immobilization concepts for reagents and catalysts including

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• of asymmetric synthesis using solid-supported catalysts is the development of an immobilization strategy that maintains both good stereoselectivity and catalyst activity. Selectivities obtained using homogeneous catalysts that work well in solution phase can often be significantly reduced when

A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed- bed microreactor

• Andrew Bogdan and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2009, 5, No. 17, doi:10.3762/bjoc.5.17

• liquids [38] have been extensively studied and are useful because the oxidation conditions are mild, selective, and the catalysts do not require regeneration. TEMPO, however, is expensive and difficult to remove from reaction mixtures. For these reasons, TEMPO immobilization is an important goal because

• it enables facile removal and recycling. We recently reported the development of an effective solid support for use in packed-bed microreactors [39], AMBERZYME® Oxirane (AO, 1), a commercially available resin with pendant epoxide functionalities designed for enzyme immobilization. AO is readily

• functionalized with a range of catalysts and works well as packing material for flow chemistry [39]. In this report, we demonstrate the immobilization of TEMPO and its use in a flow system using the Anelli-Montanari protocol for the oxidation of primary and secondary alcohols [30][40]. Our simplified reactor is

The first salen- type ligands derived from 3',5'-diamino- 3',5'-dideoxythymidine and -dideoxyxylothymidine and their corresponding copper(II) complexes

• Daniel Koth,
• Michael Gottschaldt,
• Helmar Görls and
• Karolin Pohle

Beilstein J. Org. Chem. 2006, 2, No. 17, doi:10.1186/1860-5397-2-17

• as the replacement of the thymine base by different functional groups or the immobilization of the complexes by the nucleobase enables the resulting complexes to become promising candidates as catalysts for enantioselective reactions. Conclusion In summary, an effective route for the synthesis of 3