Macrocyclic bis(ureas) as ligands for anion complexation

• Claudia Kretschmer,
• Gertrud Dittmann and
• Johannes Beck

Beilstein J. Org. Chem. 2014, 10, 1834–1839, doi:10.3762/bjoc.10.193

• Claudia Kretschmer Gertrud Dittmann Johannes Beck Institute for Inorganic Chemistry, University of Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany 10.3762/bjoc.10.193 Abstract Two macrocyclic bis(ureas) 1 and 2, both based on diphenylurea, have been synthesized. Compound 1 represents the smaller

• formation of complex building units. Tripodal tris(ureas) were synthesized, which contain tetrahedral oxoanions like phosphate or sulfate [6][7] and ligands with three concatenated urea functions were shown to form 2:2 complexes with phosphate anions [8]. Anion complexation is also possible with a rigid

• ) ligand system by cyclic bis(ureas). This opens the possibility for complexation of cations and anions with two isosteric ligands, just under exchange of the active groups within the respective ring system. Here we describe our results concerning macrocyclic bis(ureas) with a rather rigid molecular entity

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• thioformamides [28], multistep reactions involving carbonyl compounds [29][30], intramolecular electrophilic arylation of lithiated ureas [31], and Petasis-type multicomponent reaction [32][33][34] have been reported for their preparation. Although these methods propose complementary approaches to the synthesis

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• aldehydes, electron deficient alkynes and ureas/thioureas have been smoothly performed to yield a class of unprecedented 3,4-dihydropyrimidinones and thiones (DHPMs). The reactions are initiated by the key transformation of an enamine-type activation involving the addition of a secondary amine to an alkyne

• , which enables the subsequent incorporation of aldehydes and ureas/thioureas. This protocol tolerates a broad range of aryl- or alkylaldehydes, N-substituted and unsubstituted ureas/thioureas and alkynes to yield the corresponding DHPMs with specific regioselectivity. Keywords: alkynes; DHPMs; diversity

• attractiveness in biological and medicinal researches, DHPMs have also been demonstrated as quite flexible precursors for the synthesis of many other derived heterocyclic scaffolds [13]. For a rather long period, the Biginelli reaction involving the condensation of aldehydes, β-ketoesters and ureas (thioureas

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• kcal/mol). The proposed ability of squaramides to form stronger hydrogen bonds than ureas is in agreement with the experimentally found higher acidity of squaramides [28]. The strength of hydrogen bonding is also thought to be dependent on the directionality of the hydrogen bonds, with an optimum of

• in activating a hydrogen-bond-acceptor than commonly employed (thio)ureas. Synthesis of chiral open-chain PV-amides We evaluated both BINOL and chinchona alkaloids as chiral backbones. BINOL is a well-established chiral motif [30], while chinchona alkaloids are sterically very demanding, can be

• donors such as (thio)ureas in the tested Michael addition. A fine tuning of the structural motifs might improve enantioselectivity even further. Especially the rigid and sterically crowded PV-cyclodiphosphazane structures will have a high potential for future catalyst designs not only in organocatalysis

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• catalyze the enantioselective three-component reaction of mono-substituted ureas 1, alkylaldehydes 2 and arylaldehydes 3 to generate enantioenriched dihydropyrimidinones 4 [32][33][34][35]. In our initial study, we examined the multicomponent model reaction between N-methylurea 1a, phenylacetaldehyde 2a

• of this multicomponent reaction. Conclusion In conclusion, we have demonstrated the first efficient, molecular iodine-catalyzed three-component synthesis of dihydropyrimidinones starting from simple readily available mono-substituted ureas, alkylaldehydes, and arylaldehydes. A significant progress

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• )PAuOTf was employed under microwave irradiation with a catalyst loading as low as 0.05 mol %, the condensation of TsNH2 to norbornene was realized in quantitative yield. In addition, the introduction of carbene ligands [44] allowed performing the intramolecular hydroamination of N-alkenyl ureas

• (ee up to 48%, Scheme 10b). The efficiency of 33 was ascribed to double activation of the substrate by the binuclear gold complex 38. The synthetic versatility of alkenyl ureas was further demonstrated by Widenhoefer employing slightly different substrates, namely N-allyl-N’-arylureas. When 39 was

• . In 2009 Widenhoefer reported the first example of enantioselective gold-catalyzed intermolecular hydroamination of simple olefins. Firstly, the authors demonstrated that functionalization of ethylene derivatives could be conveniently accessed by using cyclic ureas 49 as nucleophiles in combination

AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldoximes with α,β-unsaturated carbonyl compounds

• Qiuping Ding,
• Dan Wang,
• Puying Luo,
• Meiling Liu,
• Shouzhi Pu and
• Liyun Zhou

Beilstein J. Org. Chem. 2013, 9, 1949–1956, doi:10.3762/bjoc.9.231

• -workers also reported many other highly functionalized isoquinoline derivatives by cascade reactions in good yields under mild conditions, such as 1-aminoisoquinolines [37] and 1-(isoquinolin-1-yl)ureas [38][39]. Recently, Deng and co-workers also described a new Pd-catalyzed C–H oxidation system for the

Self-assembly of 2,3-dihydroxycholestane steroids into supramolecular organogels as a soft template for the in-situ generation of silicate nanomaterials

• Valeria C. Edelsztein,
• Andrea S. Mac Cormack,
• Matías Ciarlantini and
• Pablo H. Di Chenna

Beilstein J. Org. Chem. 2013, 9, 1826–1836, doi:10.3762/bjoc.9.213

• stimuli such as light, ultrasound or chemical stimuli [8][9][10][11][12]. A wide variety of structurally diverse molecules have the ability to form physical gels (e.g., saccharides, peptides, ureas, nucleobases, steroids, dendrimers, etc. [13]). Although a great effort has been made to investigate the

• possess a complementary donor–acceptor hydrogen bond motif, such as for instance amides, ureas, carbamates, saccharides, ammonium carboxylate salts, etc. A rod-like molecular shape is also a general structural requirement for steroid derived LMOGs because it allows a good face to face molecular contact to

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• (to give 46 or 47 after deprotection) (Scheme 5). Finally, a selection of fluorous-tagged products was derivatised (typically on a 50 μmol scale) to yield a range of amides and ureas (Table 4). The fluorous tag facilitated the purification of the derivitised products by F-SPE. The final products 60–71

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

• Julien Lefranc Alberto Minassi Jonathan Clayden School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK 10.3762/bjoc.9.70 Abstract N-Alkenyl ureas and N-alkenyl carbamates, like other N-acyl enamines, are typically nucleophilic at their β-carbon. However, by

• incorporating an α-aryl substituent, we show that they will also undergo attack at the β-carbon by organolithium nucleophiles, leading to the products of carbolithiation. The carbolithiation of E and Z N-alkenyl ureas is diastereospecific, and N-tert-butoxycarbonyl N-alkenyl carbamates give carbolithiation

• reversed when N-acylenamines (especially N-vinyl ureas [8]) meet organolithium nucleophiles. N-Carbamoyl enamines bearing α-aryl substituents (in other words, α-acylaminostyrenes), may undergo reaction as electrophiles, with the carbon atom β to nitrogen succumbing to attack by organolithium nucleophiles

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• using DMPU as an additive to accelerate the aryl migration [17], probably by favoring the formation of solvated ion pairs [18]. Thus, this tandem enantioselective carbolithiation–rearrangement of vinylic ureas bearing an N-aryl group leads to the formation of two new carbon–carbon bonds with control of

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

• 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

• isocyanate in dimethoxyethane at 85 °C afforded urea 23 (15% yield over two steps). Reaction of compound 24 directly with benzyl isocyanate in dimethoxyethane at 85 °C afforded urea 25 in 72% yield (Scheme 1B). The hydrogenolysis of benzyl ureas 23 and 25 unexpectedly proceeded in a different manner

• dimethoxyethane at 85 °C produced ureas 28 and 29 in 47 and 50% overall yields, respectively. As previously observed, hydrogenolysis of 28 and 29 afforded monosubstituted ureas 16 and 19, with loss of the N-benzyl group. In addition, while derivative 19 was obtained with comparable purity (85%) to compound 12

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

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• for the synthesis of “nonstandard” atropisomer structures containing rigid fragments joined by a hindered single bond, but which are different from the typically well-studied biaryl compounds [4][5]. These non-biaryl atropisomers have included aromatic amides [6][7][8], ureas [9], ethers [10][11][12

• organolithium compounds having varying degrees of configurational stability [17][18], and in our studies on ureas and amides we were able to identify correlated inversion processes linking configurational inversion at organolithium centres with conformational inversion of atropisomeric chirality by bond

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

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

• extensively employed in synthetic anion receptors comprising groups such as amides, pyrroles, indoles, ureas and triazoles, as well as in ammonium, guanidinium and imidazolium moieties used as hydrogen bond donors [16][17][18][19][20][21][22][23]. Amongst neutral anion receptor systems, indole and related

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

• involves mild conditions and short reaction times. 3.3 Amides, sulfamides and ureas as nucleophiles Using AuPPh3Cl/Ag2CO3-catalyzed 5-endo-dig cyclization in water under microwave irradiation, our group developed a fast and green route to prepare indole-1-carboxamides 137 from N'-substituted N-(2

• -alkynylphenyl)ureas 136 (Scheme 25) [64]. A variety of functional groups including N'-aryl, alkyl, heterocyclic, various N-substituted-2-ethynylphenyl and N-(2-ethynylpyridin-3-yl)ureas, are tolerated and gives moderate to high yields of the desired products. In another study [65], bicyclic imidazolidin-2-ones

• 139 were obtained via gold(I)-catalyzed intramolecular dihydroamination of allenes with N,N′-disubstituted ureas 138. Iglesias et al. reported a complimentary diamination of alkenes 140 with homogeneous gold catalysts [66]. The key step is an intramolecular alkyl–nitrogen bond formation from a gold

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

• with electrophiles is general for a range of structures, but until very recently it has not been applicable to arylation reactions. However, we have discovered [75] a variant of a rearrangement reaction of lithiated ureas that we first reported in 2007 [76] in which a lithiated thiocarbamate undergoes

• an intramolecular aryl transfer. Treatment of an N-aryl S-benzyl thiocarbamate 92 leads to formation of a lithio derivative 93 comparable with those reported by Hoppe (Scheme 32). As in the case of lithiated N-aryl ureas [76][77][78][79][80] and N-aryl carbamates [81][82], the N-aryl ring is

• to a range of products 96 (Table 1) and amounts to an intramolecular arylation, allowing the formation of otherwise inaccessible doubly benzylic tertiary thiols in enantiomerically enriched form from benzylic alcohols 91. Similar to the rearrangement of lithiated ureas [76] (but interestingly in

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

• 11 shows two sets of three lines at δ 61.1, 61.7 and 62.2 and at δ 25.7, 25.9 and 26.1, respectively. The triamino-substituted TBTQs 10 and 11 readily added three equivalents of phenylisocyanate to give the corresponding C3- and C1-symmetrical TBTQ-based tris-ureas 5 and 6 in very good yields (Scheme

• identical mass spectra that clearly showed the expected [M + H]+ peaks at m/z 739 along with very minor signals for the twofold condensation product. However, the 1H NMR spectra of compounds 5 and 6 gave no hint to such impurities. In analogy to the triamino precursors 10 and 11, the TBTQ-tris-ureas 5 and 6

• pronounced magnetic anisotropy effects. In the case of the peripheral TBTQ tris-ureas 5 and 6, 1H NMR measurements in DMSO and tetrachloroethane revealed a surprising effect which may also be attributed to aggregation of these molecules in low-polarity solvents. Both of these compounds were found to be only

Fluorometric recognition of both dihydrogen phosphate and iodide by a new flexible anthracene linked benzimidazolium-based receptor

• Kumaresh Ghosh and
• Debasis Kar

Beilstein J. Org. Chem. 2011, 7, 254–264, doi:10.3762/bjoc.7.34

• hydrogen bond donors and acceptors are of considerable importance. Among the different binding motifs for anions, the hydrogen bonding properties of NH groups in neutral amines [13], amides [14], ureas/thioureas [15][16], indoles [17][18][19] and pyrroles [20] as well as in guanidinium [21] and imidazolium

Chain stopper engineering for hydrogen bonded supramolecular polymers

• Thomas Pinault,
• Bruno Andrioletti and
• Laurent Bouteiller

Beilstein J. Org. Chem. 2010, 6, 869–875, doi:10.3762/bjoc.6.102

• viscosity of these solutions can be controlled by adding monofunctional compounds, which interact with the chain extremities: chain stoppers. We have synthesized new substituted ureas and thioureas and tested them as chain stoppers for a bis-urea based supramolecular polymer. In particular, the bis-thiourea

• analogue of the bis-urea monomer is shown not to form a supramolecular polymer, but a good chain stopper, because it is a strong hydrogen bond donor and a weak acceptor. Moreover, all substituted ureas tested reduce the viscosity of the supramolecular polymer solutions, but the best chain stopper is

• [33]. The rigidity of the cyclic ureas forbids any conformational rearrangement and should make it possible to probe whether the presence of NH functions in S1 significantly affects the chain stopper efficiency. In order to see if both urea carbonyls in S2 interact cooperatively with EHUT assemblies

Anion receptors containing thiazine-1,1-dioxide heterocycles as hydrogen bond donors

• Hong-Bo Wang,
• James A. Wisner and
• Michael C. Jennings

Beilstein J. Org. Chem. 2010, 6, No. 50, doi:10.3762/bjoc.6.50

• of nitrogen-based hydrogen bond donor groups such as amides [3][4], ureas [5], pyrroles/indoles/carbazoles [6][7] and sulfonamides [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] to complex the anionic targets in a topologically complementary fashion. Sulfonamides are an interesting

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

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• activities, probably due to the presence of a hydrophilic sugar substituent at the nitrogen atom of the nor-tropane ring [71][72]. Several groups have shown that disaccharide ureas and carbamates with different bridging positions as α/β-anomers are readily accessible by the coupling reaction of aminosugars

• monosaccharide units in glycooligomers is particularly attractive with regard to molecular recognition processes. Like thioureas and ureas, guanidines can also form bidentate hydrogen bonds. In addition, because of their positively charged character, guanidines can exert strong electrostatic interactions with

Asymmetric synthesis of biaryl atropisomers by dynamic resolution on condensation of biaryl aldehydes with (−)-ephedrine or a proline- derived diamine

• Ann Bracegirdle,
• Jonathan Clayden and
• Lai Wah Lai

Beilstein J. Org. Chem. 2008, 4, No. 47, doi:10.3762/bjoc.4.47

• ] and ureas [18][19][20], we have explored the opportunities offered by dynamic kinetic [21][22][23] and dynamic thermodynamic [24] resolution [11][16][25][26][27][28][29][30]. We reported methods for the latter based on resolving “auxiliaries” which include silylethyl groups [28], proline-derived