Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• desirable products (Scheme 2, 13 to 18, up to 97% ee) with 50% aqueous K2HPO4 as base. However, under the same conditions, the PTCs with a free 9-OH (OC-17) led to 13 in low yields and enantioselectivities (21% ee). The urea catalyst OC-19 proved to be very inefficient and afforded 13 in 10% yield with 6

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• -oxathiazoline intermediate that readily rearranges into urea and eliminates the desired isothiocyanate product [37][38] (Scheme 1b). Whilst this approach appears on initial inspection to be very attractive it is somewhat hampered by the requirement to access the reactive nitrile oxide species, which once formed

Structures of the reaction products of the AZADO radical with TCNQF₄ or thiourea

• Hideto Suzuki,
• Yuta Kawahara,
• Hiroki Akutsu,
• Jun-ichi Yamada and
• Shin’ichi Nakatsuji

Beilstein J. Org. Chem. 2013, 9, 1487–1491, doi:10.3762/bjoc.9.169

• the reaction product of AZADO and thiourea We next tried to perform the reaction of AZADO (2) with thiourea (4) to see if some intriguing complexes would be formed, since a lot of inclusion compounds derived from urea or thiourea are known [13]. The reaction between 2 and 4 was first tried by mixing

Aqueous reductive amination using a dendritic metal catalyst in a dialysis bag

• Jorgen S. Willemsen,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 960–965, doi:10.3762/bjoc.9.110

• signals at 1580 and 1640 cm−1 derived from the newly formed urea functionalities. The next reaction, coordination of iridium to the dendritic ligands in methanol, afforded the corresponding iridium complexes 14 and 15 in quantitative yield. In the final step, the complex was converted into the water

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• products that may be deprotected in situ to provide a new connective route to hindered amines. Keywords: carbamate; carbolithiation; carbometallation; organolithium; stereospecificity; styrene; urea; Introduction Enamines and N-acyl enamines are in general nucleophiles, reacting with electrophiles at the

• -alkenyl carbamates. Results and Discussion Simple N-alkenyl ureas 1 were prepared by a reported method [2] entailing N-acylation of an acetophenimine with an isocyanate, followed by N-alkylation of the resulting urea. When urea 1a was treated with t-BuLi or s-BuLi in THF at −78 °C for one hour, followed

• by protonation, carbolithiated products 2a and 2b were isolated in good yield (Scheme 1 and Table 1, entries 1 and 2). Similar reactivity was observed between urea 1a and less hindered organolithiums such as iPrLi or n-BuLi [3], but in THF even at −78 °C a rearrangement [14][15][16][17][18] of the

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• -dioxides are generally synthesized either by condensation of o-aminobenzenesulfonamides with urea at elevated temperature [23] or by the reaction of o-aminobenzenesulfonamide with isocyanates in DMF under reflux [24]. Although various approaches to the preparation of 1,2,4-benzothiadiazine 1,1-dioxide

Design and synthesis of a photoswitchable guanidine catalyst

• Philipp Viehmann and
• Stefan Hecht

Beilstein J. Org. Chem. 2012, 8, 1825–1830, doi:10.3762/bjoc.8.209

• 2E. The therefore necessary urea 4 can be obtained from the addition of pyrrolidine to phenylisocyanate (3). The structure of guanidine 2E was proven by NMR spectroscopy, HRMS, as well as by single-crystal X-ray structure analysis (Figure 1). To our knowledge, this is the first example of an X-ray

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

• by three-component condensations of aldehydes, urea-type substrates and enolisable carbonyl compounds. Because of the pharmacological relevance of the products, considerable research has been directed towards asymmetric approaches of these inherently chiral heterocycles [61][62][63]. Until recently

• condensation reaction in an asymmetric fashion. Using a slightly modified procedure of the thiourea-catalyzed Biginelli reaction developed by Miao and Chen [69], we chose the condensation between urea, benzaldehyde (1.5 equiv), and ethyl acetoacetate (3 equiv) to give dihydropyrimidine 20 (Table 1) as test

• (urea) concentration from 0.25 mol/L to 0.025 mol/L caused a distinct improvement of the enantiomeric excess and the enantiomer ratio of the product 20 raised from 58:42 to 72:28 (Table 1, entry 6 vs entry 10). In addition, product 20 was isolated in a slightly better yield (92%). The attempt to reduce

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

• MCA values than the ‘urea-phosphanes’ (262, 265, 272). Can MCA values be increased through integration of the P-atom into a ring system? With respect to the results obtained for a small set of cyclic phosphanes (Table 7) it appears that there is at least no general trend for cyclic and acyclic

• respective ACA values (Table 14). Most of the 3,4-diaminopyridines (58, 59, 63, 399–408) show ACA values which are roughly between 235 and 243 kJ/mol. However, the introduction of a (thio)urea moiety as in 383–387, 389–394, and 397 lowers the ACA value by 10 to 25 kJ/mol. Annelation of an additional six

Restructuring polymers via nanoconfinement and subsequent release

• Alan E. Tonelli

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

• ; inclusion compounds; nanoconfinement; organization; polymers; properties; release; urea; Introduction The behaviors and properties of polymer materials are closely related to the organizations, structures, and morphologies of their constituent chains, which can be significantly altered during their

• 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

• distinguished [20]. Finally, examination by DSC can determine whether the guest polymer has been included in the columnar CD lattice or not, by the absence or presence, respectively, of the thermal signature(s) characteristic of the polymer, i.e., Tg and/or Tm. The formation of polymer ICs with host urea (U

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• their preliminary biological evaluation as inhibitors against porcine and insect trehalase from C. riparius. Results and Discussion In previous studies by us and other research groups it was reported that 1-deoxynojirimycin (7) and its benzyl urea derivative 8 (Figure 2) [17][18] are trehalase

• possibility to synthesize a few nojirimycin and pyrrolidine derivatives bearing a benzyl urea moiety and a different alkyl substituent on the adjacent carbon (10, 11, 15 and 18, Figure 3). Thus the presence of a benzyl urea moiety was expected to be a common feature of the majority of the iminosugar

• derivatives (piperidines and pyrrolidines). However, during the final deprotection step by hydrogenolysis, the reaction resulted in the formation of the disubstituted urea 10 or, unexpectedly, monosubstituted ureas 12, 16 and 19 (Figure 3), depending on the starting material. Pyrrolidine derivatives were

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• Yagang Zhang Steven C. Zimmerman Department of Chemistry, 600 South Mathews Avenue, University of Illinois, Urbana, IL 61801, USA 10.3762/bjoc.8.55 Abstract The facile coupling of azobenzene dyes to the quadruply hydrogen-bonding modules 2,7-diamido-1,8-naphthyridine (DAN) and 7-deazaguanine urea

• orange–yellow in color. Azobenzene coupled DAN and DeUG modules were successfully used as colorimetric indicators for specific DAN–DeUG and DAN–UPy (2-ureido-4(1H)-pyrimidone) quadruply hydrogen-bonding interactions. Keywords: azobenzene dye; colorimetric indicators; 7-deazaguanine urea (DeUG); 2,7

• -diamido-1,8-naphthyridine (DAN) unit was linked to azobenzene dyes through one of its amide groups, giving compounds 5, 8, and 10, and the 7-deazaguanine urea (DeUG) unit was linked to an azobenzene dye by a Steglich esterification, giving 12, or by the copper-catalyzed azide–alkyne cycloaddition (click

Carbamate derivatives and sesquiterpenoids from the South China Sea gorgonian Melitodes squamata

• Li-Si Huang,
• Fei He,
• Hui Huang,
• Xiao-Yong Zhang and
• Shu-Hua Qi

Beilstein J. Org. Chem. 2012, 8, 170–176, doi:10.3762/bjoc.8.18

• were very similar to those of compounds 3–5 [5][6]. Compound 3 is a symmetric urea derivative that was formed from the amidation of two molecules of 4 [6]. Comparison of the NMR data of 1 with 3–5 suggested that 1 was an asymmetric urea derivative that was formed from the amidation of 4 and 5 [5][6

• = 8.0 Hz, 1H). The 1H and 13C NMR spectral data of 2 show similarities to those of 3 [5] (Table 1). Comparison of the NMR data of 2 and 3 suggests that 2 is an asymmetric urea derivative that was formed from the amidation of two molecules of 4 [5][6], and the only difference between 2 and 3 is the

• amidation position of the two molecules of 4. Based on the 1H NMR, 13C NMR HSQC, HMBC and 1H–1H COSY spectral data analysis, the structure of 2 was elucidated to be as shown above and named as obtucarbamate D. Urea derivatives are closely related in structure to carbamates. Urea is synthesized in the body

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

• implemented in flow with reasonably short residence times using a urea additive. Many researchers, including us [36][37], have found that urea [45] additives increase the rate of various proline-catalyzed reactions [46][47][48][49][50]. The role that ureas play remains unclear, and a number of hypotheses have

• been suggested. Initially, researchers gathered 1H NMR, UV, and fluorescence data to show that ureas enhance the solubility of proline through a host–guest interaction between the urea and proline carboxylate: A substrate-independent model [49][50]. However, it has been proposed that substrate–urea

• –proline interactions may also contribute to the rate enhancement [50]. Our group observed that a urea tethered to a tertiary amine increases the rate of a number of batch reactions, including the α-aminoxylation reaction [36][37]. For the α-aminoxylation reaction, we proposed that the urea promotes

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• to make mixtures containing detectable quantities of unequal pairs of diastereoisomeric derivatives. We have previously made isotopically labelled anilines [6] for related studies on oligo-urea foldamers [7][8][9]. Achiral quaternary amino acids such as Aib and its substituted congeners are powerful

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

• leads for AIDS therapies [2]. The Biginelli reaction of a β-keto ester, an aldehyde, and urea is considered as one of the most efficient ways to synthesize dihydropyrimidinones [3]. This acid-catalyzed reaction can be conducted under conventional or microwave heating [4][5]. Reported in this paper is a

• 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

A simple and convenient one-pot synthesis of substituted isoindolin-1-ones via lithiation, substitution and cyclization of N'-benzyl-N,N-dimethylureas

• Keith Smith,
• Gamal A. El-Hiti,
• Amany S. Hegazy and
• Benson Kariuki

Beilstein J. Org. Chem. 2011, 7, 1219–1227, doi:10.3762/bjoc.7.142

• compounds can be quite subtle. For example, lithiation of N,N-dimethyl-N'-(substituted phenyl)ureas can occur predominantly on the N,N-dimethyl group (e.g., for the unsubstituted, 4-methyl or 4-methoxy-compounds with t-BuLi at −20 °C) or on the ring next to the urea group (e.g., for the 4-chloro-, 4-fluoro

• observation that lithiation of N'-(2-methoxybenzyl)-N,N-dimethylurea (1) with two equivalents of t-BuLi in THF at −20 °C for 2 h followed by reactions with a range of electrophiles gave mixtures of products (Scheme 3) involving ring substitution both next to the urea-containing group (o-substitution; 47–51

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

• deshielding of ureido protons and moderate deshielding of indole NH was observed upon the addition of acetate, benzoate, bicarbonate and dihydrogen phosphate, which indicated that the predominant hydrogen bond interactions occurred at the urea donor groups. Binding of oxo-anions caused conformational changes

• recently analyzed the conformational preferences of several 2,7-disubstituted indoles with amide substituents at C2 and urea substituents at C7, which showed preference for distinct conformations in the presence and in the absence of anions [33][34][35]. In addition, indole and urea groups were strongly

• urea analogues, such as 1, this is accompanied by higher order complex formation with oxo-anions in the solid state. For example, with dihydrogen phosphate, three equivalents of receptor complex to a single anion, which has doubly deprotonated, resulting in the formation of a complex in which twelve

Scalable synthesis of (1-cyclopropyl)cyclopropylamine hydrochloride

• Sergei I. Kozhushkov,
• Alexander F. Khlebnikov,
• Rafael R. Kostikov,
• Dmitrii S. Yufit and
• Armin de Meijere

Beilstein J. Org. Chem. 2011, 7, 1003–1006, doi:10.3762/bjoc.7.113

• , otherwise the yield of 3 dropped dramatically, and the desired product was accompanied by 1,3-di(bicyclopropyl)urea (5) in up to 50% yield (Scheme 1). The structure of the latter was confirmed by an X-ray crystal structure analysis (Figure 1) [26]. The carbamate 3 was deprotected by treatment with hydrogen

• preparation of 3 was not sufficiently dried, the thermolysis in t-BuOH along with tert-butylcarbamate 3 gave the 1,3-di(bicyclopropyl)urea (5) in up to 50% yield. Compound 5 was isolated as a colorless solid after deprotection of 3 with HCl/Et2O by evaporation of the mother liquor followed by

• ); 13C NMR (62.9 MHz, CDCl3) δ 158.8 (C), 33.9 (2 C), 15.5 (2 CH), 12.6 (2 CH2), 2.8 (6 CH2); EIMS (70 eV) m/z: 219 (M+ − H), 205 (M+ − H−CH2), 191 (M+ − H−C2H4), 124 (M+ − H−NC6H9), 96 (M+ − H−NC6H9−CO), 82 (M+ − H−NC6H9−CH2−CO). Structure of 1,3-di(bicyclopropyl)urea (5) in the crystal [26

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

Tribenzotriquinacenes bearing three peripheral or bridgehead urea groups stretched into the 3-D space

• Jörg Tellenbröker and
• Dietmar Kuck

Beilstein J. Org. Chem. 2011, 7, 329–337, doi:10.3762/bjoc.7.43

• bridgeheads of the rigid, convex–concave, C3v-symmetrical molecular framework are reported. 1H NMR data point to supramolecular aggregation of these TBTQ derivatives in low-polarity solvents. Keywords: convex–concave structures; polycyclic compounds; supramolecular chemistry; tribenzotriquinacenes; urea

• of TBTQ derivatives 5–7 with three urea units located at the molecular periphery (Figure 1). Owing to the rigidity of their molecular framework, these compounds were considered of potential interest for the formation of supramolecular aggregates consisting of two or more multiply hydrogen-bonded TBTQ

• units. Research on the formation and chemical properties of host–guest compounds bearing urea units as linker groups has become an exciting field of scientific interest over the past few decades [8][9][10][11][12][13][14][15]. For example, cone-like building blocks such as those based on calix[4]arenes

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

• formation of the dibenzosemibullvalene with moderate stereoselectivity (68:32 er). In contrast, the thioureido derivative showed no such effect upon complexation of chiral anions. Keywords: dibenzobarrelenes; dibenzosemibullvalenes; di-π-methane rearrangement; supramolecular photochemistry; (thio)urea

• 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

• spectrometry. To assess whether the influence of the anions on the photoreactivity of the dibenzobarellenes is caused by complex formation, the propensity of the urea and thiourea functionalities to associate with anions was investigated by spectrophotometric titrations of selected tetrabutylammonium salts

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

Anthracene appended pyridinium amide–urea conjugate in selective fluorometric sensing of L-N-acetylvaline salt

• Kumaresh Ghosh,
• Tanmay Sarkar and
• Asoke P. Chattopadhyay

Beilstein J. Org. Chem. 2010, 6, 1211–1218, doi:10.3762/bjoc.6.139

• Kumaresh Ghosh Tanmay Sarkar Asoke P. Chattopadhyay Department of Chemistry, University of Kalyani, Kalyani-741235, India, Fax +91-33-25828282 10.3762/bjoc.6.139 Abstract A new anthracene labeled pyridinium amide–urea conjugate 1 has been designed and synthesized. The receptor shows a different

• ; pyridinium amide–urea conjugate; Introduction The design and synthesis of artificial receptors capable of recognizing α-hydroxy and N-acetyl-α-amino acid carboxylates (i.e., salts of α-amino acids) is an active area of interest in supramolecular chemistry due to the biological significance and practical

• with 4-nitrophenyl isocyanate (obtained from 4-nitroaniline by reaction with triphosgene in dry THF) in dry THF to give urea derivative 5. Subsequent reaction of 5 with 9-chloromethylanthracene under refluxing conditions in dry CH3CN gave the chloride salt 6. Anion exchange of the salt 6 with NH4PF6