Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• of 4-hydroxycoumarin in an efficient way since conversions are often in the quantitative range. Furthermore, the catalysts provide very mild pH conditions, since the pH values are in the range of 9. This is very unusual, since ordinary primary amine catalysts require strong acids as additives, which

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• assembly of the 2-nitrobenzenesulfonyl-(Nosyl, further abbreviated with Ns)-protected spermine backbone 8 on a solid phase via Fukuyama Ns strategy [51]. The next step was the Ns protection of the residual primary amine with 6.00 equiv of Ns-chloride and 12.0 equiv 2,4,6-collidine in CH2Cl2 followed by N

• (amination) a primary amine is used to substitute the bromine to give the peptoid residue. This approach avoids the use of N-terminally protected monomers, which have to be synthesized in advance. For the incorporation of the alkyne side chains we chose propargylamine as building block. A sixfold repetitive

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• phthalimide in DMF at 90 °C, affording the corresponding N-allylphthalimide. Deprotection of the phthalimide by hydrazinolysis followed by protection of the resulting primary amine as a tert-butyl-carbamate gave the Boc-protected amine 13 required for the synthesis of the substrate of the anionic cyclization

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• ester). Thus, the activated ester end of excess SPDP was reacted with the primary amine group in aminophalloidin to form an amide linkage. In general, 63 µmol aminophalloidin were dissolved in 3.4 mL H2O and 1.7 equiv SPDP, dissolved in 900 µL dimethylformamide, were added. The solution was adjusted to

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• -protected piperazine (Table 4, entry 8). The reaction works equally well for aliphatic primary amine too (Table 4, entry 7) resulting in 90% isolated yield. There was a feeble change in yield by varying the substitution on the 7-azaindole nitrogen (N1) from a methyl to an ethyl group (Table 4, entries 6–8

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• dienophiles, vinyl enol ethers, vinyl enamides, vinyl sulfides, cyclopentadienes, indenes, alkynes and enamines have been mostly used in this method [12][13][14][15][16][17][18][19][20][21][22]. β-Enamino esters [23][24][25][26], which may be readily generated in situ by the addition of a primary amine to

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• group and that of Jacobsen reported the first successful application of primary amine-thiourea organocatalysts with the synchronous dual activation of a nucleophile and an electrophile in nitro-Michael addition reactions [36][37][38][39][40][41][42]. Bifunctional organocatalysts that contain both a

• -Diaminocyclohexane (1) and (R)-1-phenylethyl isothiocyanate (2) were employed for the synthesis of primary amine-thiourea 3 [36][38][40][54]. Subsequent treatment of 3 with a guanidinylation reagent, N,N′-di-Boc-N″-triflylguanidine (4) [54][55], gave the intermediate 5 in 98% yield. The next step involved cleavage

• , 57.00, 125.39, 128.18, 128.88, 140.11 ppm. Primary amine-thiourea 3: To a solution of (S,S)-1,2-diaminocyclohexane (1) (1.273 g, 11.15 mmol, 1.0 equiv) in anhydrous dichloromethane (100 mL), at ambient temperature and under a nitrogen atmosphere, a solution of 2 (1.820 g, 11.15 mmol, 1.0 equiv) in

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• bicyclic guanidines [7][9][12]. Xiao et al. reported the addition of nitroalkanes to 4-oxo-enoates, using chiral urea derivatives [7]. Miura et al. achieved an asymmetric addition of α,α-disubstituted aldehydes to maleimides catalyzed by primary amine thiourea organocatalyst [13]. Wang et al. reported the

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• aqueous work-up followed by the addition of 3,5-bis(trifluoromethyl)phenyl isothiocyanate to each crude primary amine completed the syntheses of ethylene-linked sulfonimidoyl-containing thioureas (SS,SC)-18 and (RS,SC)-19 providing them in very good yields (98% and 87%, respectively) over two steps. One

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

• 4–9, thereby adjusting the degree of cross-linking. As for the Cinchona organocatalysts, we wanted to incorporate either unmodified quinine (1), the primary amine organocatalyst 2, or thiourea organocatalyst 3 into the thiol–ene network (Figure 1). While quinine is available directly, primary amine

• 23% ee), and probably not very useful for benchmarking, the supported catalysts 10a–d were obviously catalytically active, albeit modestly selective compared to the free catalyst, giving quantitative yields and a selectivity of 11–14% ee. Of greater interest was the performance of the primary amine

• organocatalysts 11. Polymer-supported catalysts 11a,b were tried out in the asymmetric preparation of the anticoagulant warfarin from benzylideneacetone and 4-hydroxycoumarin, a transformation that we have investigated in our group as part of developmental work in primary amine organocatalysis on a previous

Enaminones in a multicomponent synthesis of 4-aryldihydropyridines for potential applications in photoinduced intramolecular electron-transfer systems

• Nouria A. Al-Awadi,
• Maher R. Ibrahim,
• Mohamed H. Elnagdi,
• Elizabeth John and
• Yehia A. Ibrahim

Beilstein J. Org. Chem. 2012, 8, 441–447, doi:10.3762/bjoc.8.50

• -piperidinoacrylonitrile (13) with the appropriate aldehyde and primary amine under the same reaction conditions (A, B) (Scheme 4). Compounds 2a–c and 6a were readily oxidized to the corresponding pyridine derivatives 15a–d by stirring in aqueous nitric acid (70%) at 5 °C to room temperature (Scheme 5). The X-ray

• . This is a one-pot three-component reaction; on the other hand, the reported method involves two steps starting with the reaction of phenylpropynone with a primary amine, followed by reaction with different aldehydes. The synthesis of suitable substituted derivatives, such as 6 and 7, possessing

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• product. The initiation module of curacin biosynthesis contains a GCN5-related N-acetyltransferase (GNAT) domain. These enzymes typically catalyze acyl transfer to a primary amine. The curacin GNAT, however, was shown to be bifunctional and to exhibit decarboxylase/S-acetyltransferase activities [45]. The

Synthesis of dye/fluorescent functionalized dendrons based on cyclotriphosphazene

• Aurélien Hameau,
• Sabine Fuchs,
• Régis Laurent,
• Jean-Pierre Majoral and
• Anne-Marie Caminade

Beilstein J. Org. Chem. 2011, 7, 1577–1583, doi:10.3762/bjoc.7.186

• [15]. The method elaborated is also useful for the grafting of dyes, as will be illustrated with the dabsyl dye. We also paid particular attention to the nature of the remaining function (usable for the grafting of the dendron). We choose an aldehyde and a primary amine, both being well-known for

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• , giving good to excellent yields (Scheme 10) [9]. Barluenga and coworkers reported a synthesis of spiroacetals 22, through a Pd(II)-catalyzed three-component cascade reaction, starting from an alkynol, an aldehyde and a primary amine. The authors suggested that the first step of the reaction was the

• reported by Wu and coworkers. Initial Sonogashira coupling was effected between a 2-bromobenzaldehyde and an alkyne in the presence of catalytic amounts of PdCl2(PPh3)2 and CuI. After complete conversion of the aldehyde into the coupling product 25 (TLC control), a primary amine and diethylphosphite were

• substituted pyrroles involving a dihalogeno substrate and a sequential Sonogashira coupling followed by an hydroamination was developed by Duchêne and Parrain [32]. In this one-pot sequence, the first reaction is an allylic amination between the 3,4-diiodobut-2-enoic acid (54) and a primary amine, which can

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• powerful tool for the synthesis of acylated α-hydroxyacid amides [10]. Later on, in 1961, Ugi and Steinbrückner reported the extension of this protocol by incorporating also a primary amine as a fourth component [11]. Therefore, the Ugi reaction is even more flexible than the Passerini approach, but both

Reductive amination with zinc powder in aqueous media

• Giovanni B. Giovenzana,
• Daniela Imperio,
• Andrea Penoni and
• Giovanni Palmisano

Beilstein J. Org. Chem. 2011, 7, 1095–1099, doi:10.3762/bjoc.7.125

• process could be considerably simplified by the development of a one-pot procedure involving the combination of a primary amine, aldehyde, and zinc in water, thereby avoiding the isolation of the intermediate imine. Although this combination appears to be plausible, its success is far from obvious: i) the

Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

• Peter Wipf and
• Marija D. Manojlovic

Beilstein J. Org. Chem. 2011, 7, 824–830, doi:10.3762/bjoc.7.94

• methodology, we demonstrated that the homoallylic amine products could be readily converted to synthetically useful building blocks, such as β-amino acids (Scheme 4). N-Boc-protection of the primary amine 12 followed by ozonolysis under Marshall’s conditions [40] yielded the β-amino acid derivative 24. The

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• synthetic approach was based on the classical Paal–Knorr cyclocondensation of a highly substituted 1,4-diketone with a primary amine bearing a masked aldehyde functionality. The 1,4-diketone component, which can be accessed via a 3-step sequence [5] starting from aniline, was refluxed with 3

• the indole ring and the pendant primary amine group in a single operation (Scheme 17). However, the main disadvantage of this process is the need for high temperatures which leads to the formation of dimeric impurities and results in the requirement for extensive chromatographic purification. An

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• catalytic synthetic sequence is an inexpensive and efficient route to the target compounds (Scheme 12) [64]. A three-component coupling reaction of 2-bromobenzenethiol 57, a primary amine 58 and 1-bromo-2-iodobenzenes 59, also targeting promazine derivatives 60, was successfully under palladium catalysis

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

• methacrylate (SIMA (S), Figure 1) as an active ester-functional monomer in DMSO by using surface-modified Fe3O4 nanoparticles as macroinitiators (Scheme 1). Subsequently, subunits carrying primary amine groups, such as proteins or enzymes, can be immobilized via the active ester pendant groups of the brush

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors

• Georg Schitter,
• Elisabeth Scheucher,
• Andreas J. Steiner,
• Arnold E. Stütz,
• Martin Thonhofer,
• Chris A. Tarling,
• Stephen G. Withers,
• Jacqueline Wicki,
• Katrin Fantur,
• Eduard Paschke,
• Don J. Mahuran,
• Brigitte A. Rigat,
• Michael Tropak and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2010, 6, No. 21, doi:10.3762/bjoc.6.21

• substituent. For the synthesis of compound 16, 4-isopropylbenzoic acid was reacted with the primary amine under amide coupling conditions with O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoro-borate (TBTU) as the coupling reagent in DMF and triethylamine. Likewise, nicotinic acid under the same

• )-1-deoxygalactonojirimycin (15) from 12 via 14. Synthesis of lipophilic 1-deoxy-D-galactonojirimycin derivatives 16–18 by chemoselective acylation of 15. Synthesis of compounds 19 as well as 20 from primary amine 15. Synthesis of compound 22. Inhibitory activities of compounds 16–20 and 22 with β

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• which provided the products with high enantioselectivities. Beside indoles, anilines have gained much attention as target for hydroarylation reactions. However, the main issues for FC alkylations of anilines are the deactivation of the catalyst due to coordination of the primary amine and/or concurrent

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• requisite eight membered ring was formed by the well-established chemistry of quinones using an intramolecular Michael addition by the primary amine 157 (Scheme 44) [118]. The synthesis began with the known phenol 158 which was reacted with allyl bromide to trigger a Claisen rearrangement (Scheme 45). This

• selectively reduced to the corresponding amine with stannous chloride and thiophenol and the aziridine was fashioned by protection of the primary amine followed by an intramolecular Mistunobu reaction. The tetracyclic framework was completed by an intramolecular Michael addition to give desmethoxymitomycin A

N-acylation of ethanolamine using lipase: a chemoselective catalyst

• Mazaahir Kidwai,
• Roona Poddar and
• Poonam Mothsra

Beilstein J. Org. Chem. 2009, 5, No. 10, doi:10.3762/bjoc.5.10

• ) the high reactivity of primary amine, (ii) the fact that use of excess fatty acid or ester 1a–h is not required to convert virtually all the amine to its ion-pair form and (iii) in aminoalkanols NH2(CH2)nOH, where n < 3, there is migration of acyl groups from O→N spontaneously when excess of fatty