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

• , by a factor of >100. Linked by a thiourea moiety, as in compound 3, the fluorescent moiety is not cleaved inside the cell, as concluded from the observation that this phalloidin derivative still decorates filaments in the cell. This property of rhodamine-labeled phalloidin seems useful as a tool for

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• poor enantioselectivity (5–17% ee) (Scheme 16). Very recently, Schreiner et al. [63] reported a bifunctional thiourea XXXIb catalyzed tandem reaction of salicyl-N-tosylimines 33 with nitroolefins 27 in toluene at room temperature for the synthesis of nitrochromenes 28, which resulted in poor yield and

• pyrrolidine derivatives XIV (Scheme 20). In 2007 Wang et al. [67] presented a hydrogen-bond-mediated catalysis in order to perform highly enantio- and diastereoselective tandem Michael–aldol reactions for the synthesis of thiochromene derivatives. In a very low catalyst loading (<1 mol %) of hybrid thiourea

• bioactive succinimide-containing benzothiochromenes by condensation of 2-mercaptobenzaldehydes 34 with maleimides 42 catalyzed by a bifunctional chiral amine thiourea XXXVII. Mechanistically, the reaction proceeded through a hydrogen-bond-mediated activation mechanism by using 1 mol % catalyst loading

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

• Organic Chemistry I, University of Erlangen-Nuremberg, Henkestraße 42, 91054, Erlangen, Germany 10.3762/bjoc.8.168 Abstract A new guanidine-thiourea organocatalyst has been developed and applied as bifunctional organocatalyst in the Michael addition reaction of diethyl malonate to trans-β-nitrostyrene

• . Extensive DFT calculations, including solvent effects and dispersion corrections, as well as ab initio calculations provide a plausible description of the reaction mechanism. Keywords: bifunctional organocatalyst; DFT calculations; guanidine-thiourea; Michael addition; organocatalysis; transition states

• ; Introduction In recent years bifunctional compounds have found frequent applications as organocatalysts in modern synthetic organic chemistry [1][2][3][4][5][6][7][8]. Over the past decade, different catalytic methodologies have been reported that use chiral thiourea-based bifunctional molecules [9][10][11][12

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

• unsaturated 1,4-diketones catalyzed by thiourea and squaramide derivatives with Cinchona alkaloids afforded the formation of a new C–C bond in high yields (up to 98%) and enantiomeric purities (up to 93%). The absolute configuration of the product was suggested from comparison of the experimental and

• calculated VCD spectra of the reaction product 3a. Keywords: Michael addition; non-covalent catalysis; organocatalysis; squaramide; thiourea; Introduction The asymmetric 1,4-conjugated addition (Michael reaction) of C-nucleophiles to enones is a powerful tool for obtaining a significant variety of

• 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

• Marcus Frings Isabelle Thome Carsten Bolm Institut für Organische Chemie, Landoltweg 1, RWTH Aachen University, 52074 Aachen, Germany 10.3762/bjoc.8.164 Abstract For the first time, chiral sulfoximine derivatives have been applied as asymmetric organocatalysts. In combination with a thiourea-type

• backbone the sulfonimidoyl moiety leads to organocatalysts showing good reactivity in the catalytic desymmetrization of a cyclic meso-anhydride and moderate enantioselectivity in the catalytic asymmetric Biginelli reaction. Straightforward synthetic routes provide the newly designed thiourea-sulfoximine

• reactions in a highly enantioselective manner has no end in sight. In this context, thiourea-based organocatalysts have caught significant attention due to their ability to activate substrates through hydrogen-bonding [42][43][44][45][46][47]. Usually, these chiral thioureas are classified into several

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• pivaloylamido group (α, β, γ). The resulting MCA values vary by about 18 kJ/mol. Besides these amide-containing phosphanes (thio-)urea-containing phosphanes were also investigated. They possess lower MCA values than the previously discussed ones. In general, the ‘thiourea-phosphanes’ (258, 263) show even lower

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• that other groups have used thiourea-derivatives as successful catalysts [32], we decided to test, on a model system, whether these catalysts could increase the reaction rate based on specific hydrogen bonds. In our initial screening we used the proven Schreiner catalyst 1,3-bis(3,5-bis(trifluoromethyl

• )phenyl)thiourea, which gave a satisfying 60% yield. In order to optimize the yield and to introduce chiral elements, we screened a number of analogues. These thiourea catalysts 9a–l were easy to obtain from the corresponding isothiocyanates 7a,b and chiral amines 8a–f in a one-step synthesis (Scheme 1

• from 68% to 99% depending on the substitution of the thiourea-catalyst 9a–l (Table 2). When the substitution of the various thioureas 9a–l is further compared with the obtained yields in the Diels–Alder reaction (Table 2), the following tendencies are also observed. A noticeable fact is that, in

Restructuring polymers via nanoconfinement and subsequent release

• Alan E. Tonelli

Beilstein J. Org. Chem. 2012, 8, 1318–1332, doi:10.3762/bjoc.8.151

• coalesced bulk polymer sample. This process is illustrated in Figure 1, in which the cyclic starches, cyclodextrins (CDs), are the host molecules used to form ICs with guest polymers [1][2]. In polymer ICs formed with CDs and other small-molecule hosts, such as urea, thiourea, cyclotriphosphazenes, and

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• , catalyzed by cinchonine-derived bifunctional thiourea catalyst has been described. The desired β-amino ketones were obtained in excellent yields and with moderate to good enantioselectivities. Keywords: decarboxylative addition; β-keto acid; Mannich reaction; organocatalysis; Introduction Chiral β-amino

• , entry 1). Quinine-derived sulfonamide [40], β-isocupreidine (β-ICD) [41][42] and biscinchona alkaloid (DHQ)2AQN were all found to be poor catalysts (Table 1, entries 2–4). On the other hand, cinchona alkaloid derived bifunctional thiourea tertiary amine catalysts afforded much improved results (Table 1

• , entries 5–7). Among them, the cinchonine based thiourea C-1 turned out to be the best catalyst, and the Mannich product was isolated with 58% ee (Table 1, entry 7). In addition, we also examined several other bifunctional catalysts based on amino acids [43][44], including threonine derived Thr-1 [45], and

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• intermediates 26–28 is described in Scheme 2. First, acceptors 23–25 were prepared in good yields through the selective removal of the chloroacetate (thiourea) in disaccharides 20–22. Fucosylation of acceptor 23 with ethylthioglycoside 12 was first attempted under NIS and TMSOTf activation at low temperature

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

• organocatalyst 2 was prepared from quinine, via the azide, in a two-step sequence by using the Bose–Mitsunobu reaction followed by Staudinger reduction, as described by others [15]. Thiourea Cinchona organocatalyst 3 was easily obtained from catalyst 2 by reaction with the appropriate aromatic isothiocyanate [15

• supported thiourea catalyst 12 in the Michael addition of thiophenol and cyclohex-2-enone [17], a transformation known to be very efficiently catalysed by the free thiourea catalyst 3 (Table 3) [19][20]. The immobilized catalyst 12 proved highly active (the uncatalysed reaction is very slow), rapidly giving

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• of Chemistry & Molecular Engineering, East China University of Science and Technology, and 130 MeiLong Road, Shanghai 200237, People’s Republic of China 10.3762/bjoc.8.121 Abstract We have developed a multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman

• previous literature. Keywords: asymmetric [3 + 2] annulation; maleimides; Morita–Baylis–Hillman carbonates; multifunctional thiourea-phosphine; organocatalysis; Introduction Highly functionalized cyclopentene derivatives are important subunits in a variety of biologically active molecules and have

• intermolecular [3 + 2] cycloaddition of MBH carbonates with methyleneindolinones to afford the corresponding spirocyclopentaneoxindoles in good yields and high ee values in 2011 [49]. Moreover, Lu and co-workers have recently explored a series of thiourea-phosphine catalysts derived from L-threonine, which are

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• chloroacetamide with thiourea gave the free amine [21], which was then protected with Boc anhydride. Finally, cross metathesis with ethyl acrylate furnished the desired compound 4 in 24% overall yield. Cyclisation reactions The first attempts at the tandem Boc-deprotection/bicyclisation of these substrates were

Enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes catalyzed by binaphthyl-derived organocatalysts

• Saet Byeol Woo and
• Dae Young Kim

Beilstein J. Org. Chem. 2012, 8, 699–704, doi:10.3762/bjoc.8.78

• addition. This reaction exhibited good yield and high enantioselectivity (89% ee, Table 1, entry 1). In order to enhance the enantioselectivity, other bifunctional organocatalysts II–VIII were evaluated in the model reaction (Table 1, entries 2–8). The quinine-derived thiourea catalyst II was less

• the desired product 3a with high enantioselectivity (97%, Table 1, entry 3), whereas the diastereomeric catalyst VII afforded product 3a in lower enantioselectivity (78% ee, Table 1, entry 7). These results demonstrate that the central and axial chiral elements in the chiral amine-thiourea catalyst

• (97% ee, Table 2, entry 11). In conclusion, we have developed a highly efficient catalytic, enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinone to nitroalkenes using a binaphthyl-derived tertiary amine-thiourea organocatalyst. The various types of nitroalkylated naphthoquinone

Continuous proline catalysis via leaching of solid proline

• Suzanne M. Opalka,
• Ashley R. Longstreet and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2011, 7, 1671–1679, doi:10.3762/bjoc.7.197

• homogeneous catalyst can be prepared continuously via reaction with a packed-bed of a catalyst precursor. Specifically, we perform continuous proline catalyzed α-aminoxylations using a packed-bed of L-proline. The system relies on a multistep sequence in which an aldehyde and thiourea additive are passed

• . Keywords: aminoxylation; flow chemistry; heterogeneous catalysis; packed-bed microreactor; proline/thiourea catalysis; Introduction Continuous flow chemistry [1][2][3], performed in small dimension tubing or channels, differs from batch chemistry in that mixing and heat transfer are significantly faster

• combined with nitrosobenzene in the coil, the desired product was not detected by crude 1H NMR analysis (Table 1, entry 1). This indicates that, with this reactor setup, the reaction is too slow without a urea additive to be a viable method. Additionally, flowing thiourea 3b (0.047 M in EtOAc) through the

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• by the reaction of phenols with perfluorooctanesulfonyl fluoride, by following the reported procedure [13]. Compounds 1 were used as a limiting agent to react with urea/thiourea 2 and acetylacetone 3 for the Biginelli reactions. The reactions were promoted by Yb(OTf)3 as a catalyst [14][15

NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

• Damjan Makuc,
• Jennifer R. Hiscock,
• Mark E. Light,
• Philip A. Gale and
• Janez Plavec

Beilstein J. Org. Chem. 2011, 7, 1205–1214, doi:10.3762/bjoc.7.140

• hydrogen bonds stabilize the PO43− anion. In solution, the thiourea analogues such as compound 2 show significantly lower affinities for oxo-anions than do the urea analogues. We had previously proposed that this may be due to the larger size of the sulfur atom resulting in a lower propensity of these

• anion binding relative to thiourea 2 (the data were supported by the stability constant determinations performed previously and shown in Table 1). The larger sulfur atom can prevent the receptor 2 from adopting a planar conformation, which may reduce the affinity of this receptor for anionic guests

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• ee values have been obtained with thiourea-cinchonine [176], chiral carbene [177], BINAP [178][179][180], and BIPHEP [181][182][183][184][185][186][187][188][189][190] analogs. Monge et al. reported a direct asymmetric one-pot synthesis of optically active 2,3-dihydropyrroles from propargyl

• malononitriles 375 and N-Boc-protected imines 374 (Scheme 60) [176]. In the alkyne hydroamination (which is based on a bifunctional organocatalytic Mannich-type reaction, subsequent gold-catalyzed alkyne hydroamination and isomerization) thiourea-based hydrogen bonding organocatalyst 373 and PPh3AuNTf2 proved to

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• of the enantiomers of hindered enone 46 by addition, oxidation and elimination of a sulfenic acid under basic conditions (Scheme 18) [45]. Xiao and co-workers developed an organocatalytic process for the addition of thiols to nitroalkenes [46]. Using thiourea organocatalyst 48, conjugate addition of

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

Air-stable, recyclable, and time-efficient diphenylphosphinite cellulose-supported palladium nanoparticles as a catalyst for Suzuki–Miyaura reactions

• Qingwei Du and
• Yiqun Li

Beilstein J. Org. Chem. 2011, 7, 378–385, doi:10.3762/bjoc.7.48

• ], N-heterocyclic carbenes [13][14][15], P,O-based ligands [16], bis(thiourea) ligands [17], and thiosemicarbazone [18], etc. However, the separation of the catalyst and ligands from the final product is problematic. In this regard, studies on heterogeneous catalysts have drawn much attention because

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• , however, are efficiently transformed to the dibenzosemibullvalene product upon irradiation, presumably by suppressing the self-quenching of the thiourea units in the complex. The association of the ureido-substituted dibenzobarrelene derivative with (S)-mandelate and irradiation of this complex led to the

• latter in solution. For that purpose the dibenzobarrelene chromophore was functionalized with ureido or thioureido substituents, since these functionalities are strong hydrogen bonding donors, which may associate with (chiral) anions [38][39]. Moreover, the versatile use of urea and thiourea derivatives

• -substituted derivatives 1h and 1i have significantly improved solubility in organic solvents; i.e., compound 1h has good solubility in acetone, acetonitrile and alcohols, while thiourea 1i dissolves in most polar organic solvents. Because of their favorable solubility in organic solvents, the dibenzobarrelene

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

• Benan Kilbas and
• Metin Balci

Beilstein J. Org. Chem. 2011, 7, 246–253, doi:10.3762/bjoc.7.33

• of 6 [18]. Selective reduction of the peroxide linkage in 6 was carried out with thiourea under very mild conditions to give the diol 7 [19]. Since only the oxygen–oxygen bond is broken in this reaction, the configuration at all carbon atoms is preserved. Oxazolidinone 9 was synthesized by two

• than the trans-coupling [23][24], we assigned the exo-configuration to the cyano group in 12. Selective reduction of the peroxide linkages in 12 and 13 with thiourea under very mild conditions afforded the diols 14 and 18a, respectively. For further characterization, the diols were converted to the

• , 56.08; H, 4.67; N, 3.85; S, 8.63. rel-(1R,2S,5R,6S)-2,5-Dihydroxybicyclo[4.1.0]hept-3-ene-7-exo-carbonitrile (14): To a magnetically stirred solution of endoperoxide 12 (1.00 g, 6.71 mmol) in MeOH/CHCl3 solution (30 mL), was added thiourea (513 mg, 6.75 mmol) over a 10 min period at room temperature and

An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids

• Xiao-bo Zhou,
• Yuk-Wang Yip,
• Wing-Hong Chan and
• Albert W. M. Lee

Beilstein J. Org. Chem. 2011, 7, 75–81, doi:10.3762/bjoc.7.11

• Xiao-bo Zhou Yuk-Wang Yip Wing-Hong Chan Albert W. M. Lee Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China 10.3762/bjoc.7.11 Abstract Two mesitylene based neutral receptors 1 and 2 bearing two thiourea binding sites were constructed as fluorescent probes

• molecular platform via thiourea formation to give the key intermediate 4 in 70% yield. As a result of steric hindrance, an attempt to make the corresponding bis-thiourea adduct from 3 and 9-aminomethylanthracene was unsuccessful. However, 4 underwent a smooth addition reaction with the structurally less

• charge neutral thiourea-based fluorescent PET sensor motif, which is immune from cross pH interference, was adopted in our approach [28]. The congested mesitylene derivative type of structure built in 1 may confer the molecule with sufficient rigidity favoring its selective binding with guest molecules

A new fluorescent chemosensor for fluoride anion based on a pyrrole–isoxazole derivative

• Zhipei Yang,
• Kai Zhang,
• Fangbin Gong,
• Shayu Li,
• Jun Chen,
• Jin Shi Ma,
• Lyubov N. Sobenina,
• Albina I. Mikhaleva,
• Guoqiang Yang and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2011, 7, 46–52, doi:10.3762/bjoc.7.8

• reported in recent years, those employing polarized NH groups as anion-binding motifs have attracted considerable attention. Typical examples are charge neutral receptors containing pyrrole, amide, indolocarbazole, guanidium, imidazolium and urea/thiourea moieties. Usually, the anions are recognized via H

• -bonding, which is not easy to differentiate from deprotonation of protons on the receptor-NH [4][5]. Some urea/thiourea-containing receptors could particularly recognize Y-shaped oxoanions by H-bonding and more basic anions such as fluoride by deprotonation. Fluoride is primarily used for prevention of

• advantageous to develop high-effective sensors that can detect fluoride anion in food and animal feed. In this work, we report a new fluoride receptor 1 (Figure 1), 3-amino-5-(4,5,6,7-tetrahydro-1H-indol-2-yl)isoxazole-4-carboxamide [9], which contains receptive groups toward anions and no urea/thiourea