Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• 2015. Review 1 Biginelli condensation The classical Biginelli condensation involves the reaction of an aldehyde 1 with urea (2) and a β-ketoester 3 under acidic conditions in refluxing ethanol to yield 3,4-dihydropyrimidin-2-one derivatives 4 (Scheme 1) [24]. Although, a large number of CH-acidic

• were resistant to this reaction. The trimethylchlorosilane-mediated one-pot reaction of diethyl (3,3,3-trifluoropropyl-2-oxo)phosphonate (8) with aryl aldehydes 9 and urea under Biginelli conditions has been presented by Timoshenko et al. (Scheme 3) [27]. The resulting 4-hydroxytetrahydropyrimidin-2

• reaction of diethyl (3,3,3-trifluoropropyl-2-oxo)phosphonate. Biginelli reaction of dialkyl (3,3,3-trifluoropropyl-2-oxo)phosphonate with trialkyl orthoformates and urea. p-Toluenesulfonic acid-promoted Biginelli reaction of β-ketophosphonates, aryl aldehydes and urea. General Kabachnik–Fields reaction for

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• readily available joint urea-type substrate enables the facile preparation of both diastereomers in high yields. The practical application of this approach is demonstrated in the efficient and modular preparation of the authentic heterocyclic cores of manzacidins, structurally unique bromopyrrole

• -metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid. Keywords: cross-metathesis; natural products; pyrimidines; Tsuji–Trost reaction; synthetic methods; Introduction Chiral pyrimidine motifs constitute prevalent structural

• ][30][31], we became interested to devise a novel and a more versatile route to the central heterocyclic core of these marine metabolites. The method is based on a late-stage diversification strategy involving a Tsuji–Trost reaction of the urea-type joint precursor 5. In contrast to existing routes

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• stereochemical configuration of the quaternary carbon was established by a diastereoselective Michael addition between a chiral, single enantiomer, cyclic β-amido ester and a nitroolefin, and, in the case of nakadomarin A the reaction could be rendered catalytic using a bifunctional cinchonine-derived urea

Iodine-mediated synthesis of 3-acylbenzothiadiazine 1,1-dioxides

• Long-Yi Xi,
• Ruo-Yi Zhang,
• Lei Shi,
• Shan-Yong Chen and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2016, 12, 1072–1078, doi:10.3762/bjoc.12.101

• been developed to synthesize benzothiadiazine 1,1-dioxides and their analogues. The condensations of 2-aminobenzenesulfonamides with urea, isocyanates, carboxylic acid derivatives or other carbonyl reagents are the most used methods [12][13][14][15]. These reactions were usually carried out under harsh

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• under milder conditions than those previously reported. The nature of the directing group was found to be critical for achieving room temperature conditions, with the urea moiety the most effective in promoting facile coupling reactions at an ortho C–H position. This methodology has been utilized in a

• group as has been observed in a related urea palladacycle [73][215]. The bond length of Pd–N is 1.96 Å in [Pd(MeCN)4](BF4)2. NMR spectroscopic studies on the reaction between a cationic Pd(II) complex and an arylurea to generate a palladacycle are illustrated in Figure 8. The pure palladacycle from pre

• coordinating ability as a ligand on cationic palladium. On the other hand, when nitrile-free conditions were applied to urea 1f, with in situ-generated palladacycle (from Pd(OAc)2 and HBF4; Figure 8), followed by addition of the usual reagents, each reaction proceeded to give the anticipated acrylated/arylated

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• yields (70–84%) and with decreased enantioselectivities (37–83% ee, Scheme 32) [49]. Zhao and co-workers developed the first enantioselective aldol reaction of 3-acetyl-2H-chromen-2-ones with isatins catalyzed by the quinidine-derived urea catalyst (cat. 18, Scheme 33) [50]. The reactions were performed

• catalyst loading at –20 °C. They also highlighted another cinchona alkaloid-derived urea catalyst bearing an N-alkyl group (cat. 20), which was more efficient than cat. 19 in the reactions with halogenated isatins. Compared to N-unsubstituted isatins, the N-methyl-protected isatin gave a lower yield and ee

• yields and enantioselectivities. (Thio)urea catalysts Different from the above mentioned aldol reactions, Jiang and co-workers reported the first highly enantioselective vinylogous aldol reaction of allyl ketones with isatins (Scheme 39) [56]. The reactions were performed in diethyl ether in the presence

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• (Scheme 8) [85]. This catalyst belongs to a new subclass of bifunctional Brønsted bases, which was developed on the basis of Takemoto’s model [86]. This model is featured by three different moieties: a basic site, a urea (thiourea) function and a 3,5-bis(trifluoromethyl)phenyl group, all three elements

• to develop hydrogen bond interactions [92][93][94][95] with a Brønsted base could provide a new family of potentially efficient bifunctional catalysts (Figure 4b). The main features of these new catalysts are the presence of a urea moiety together with a N,N-diacylaminal unit, both in close proximity

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• well as FT mass spectrometry [22]. Muraymycins have a glycyl-uridine motif, which is connected via an aminopropyl linker to a urea peptide moiety consisting of L-leucine or L-hydroxyleucine, L-epicapreomycidine (a non-proteinogenic cyclic arginine derivative) and L-valine. The uridine structure is

• [35]. In comparison to the muraymycins, only the urea peptide moiety and the lipopeptidyl motif are absent. The mureidomycins [36][37][38] and pacidamycins [39][40][41], both reported in 1989, the napsamycins (1994) [42] and the sansanmycins (2007) [43][44] are structurally closely related. They

• either methionine for mureidomycins, napsamycins and sansanmycins or alanine in case of pacidamycins. Remarkably, these natural products share a urea peptide motif with the muraymycins. They are mainly active against Gram-negative bacteria, which is a noteworthy difference to the muraymycins and other

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• aerobic conditions with copper salt catalysts [67]. For example, when the antipsychotic drug aripiprazole (96) was treated with a catalytic amount of CuI under air or oxygen in DMSO at 120 °C, 2,3-diketopiperazine 97 was produced in 30% yield along with a 15% yield of urea product 98 (Figure 16). This

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• formation of catalytically active oxazaborolidines using cis-1,2-aminoindanol derivatives [9][10] and (b) the synthesis of more active cooperative thiourea-urea-based organocatalysts, which employ the aminoindanol framework as structural linker between two hydrogen-bond-donor moieties [11]. The latter ones

• acting through hydrogen bonding, such as thiourea, urea, squaramide, and thioamide frameworks. These have been efficiently employed in a few organocatalytic processes such as Friedel–Crafts alkylations, Michael additions, Diels–Alder reactions and aza-Henry reactions, as discussed below. Friedel–Crafts

• biologically interesting β-amino acid derivatives (Table 2) [42]. In this work, the authors compared the results achieved by means of 4 with other urea- and thiourea-based organocatalysts in order to understand the effect of the acidity, the structural rigidity, and the bifunctionality of the promoter. These

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• chiral centers; organocatalysis; six-membered ring; thiourea; urea; Introduction During the last 15 years, organocatalysis has flourished and has been established as one of the three major pillars of asymmetric synthesis [1][2][3]. Among the modes of activation of organic molecules that have been

• involves hydrogen bonding, which is also postulated to be present in enzymatic reactions. (Thio)urea moieties have been employed in order to activate electrophiles and in order to allign them, in a specific manner, so as to react with nucleophiles (Scheme 3) [6][7]. In addition, many bifunctional (thio

• [10][11][12][13][14]. This review will focus on (thio)urea organocatalysts, including primary, secondary and tertiary amine groups. Miscellaneous catalysts will be also presented. Thus, it will provide an exhaustive overview of this area, rather than providing a few examples of each class of

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• developed the pyroglutamic acid-derived triazolium salt 10 which mediated benzoin reactions in similar enantioselectivities [14]. The chiral triazolium catalyst 11 transfers chiral information to the benzoin products by engaging in hydrogen-bonding interactions [15]. Waser’s chiral bifunctional (thio)urea

• a cross-benzoin reaction of the latter to furnish the spirocyclic product 84 (Scheme 46). Conclusion The first report of a benzoin reaction by Wöhler and Liebig appeared merely four years after the former disclosed the paradigm-changing urea synthesis. However, detailed investigations of this

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• preliminary study on sonochemical Staudinger-aza-Wittig tandem reactions [20] proving that isocyanate and urea formation is strongly favored. However, the applied power must be optimised for the best conversions of azido-CD into urea to be obtained and if lower efficiency in the second step is to be avoided

Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

• Minami Odagi,
• Yoshiharu Yamamoto and
• Kazuo Nagasawa

Beilstein J. Org. Chem. 2016, 12, 198–203, doi:10.3762/bjoc.12.22

• presence of a guanidine–bisurea bifunctional organocatalyst was investigated. The α-amination products were obtained in up to 99% yield with up to 94% ee. Keywords: α-amination; bifunctional catalyst; guanidine; hydrogen-bonding catalyst; urea; Introduction Asymmetric α-amination of β-keto esters is an

• particular, catalytic asymmetric α-amination of β-keto esters has been widely explored, using both metal catalysts and organocatalysts [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. We have developed a series of guanidine–bis(thio)urea bifunctional organocatalysts, and have used them in a variety of

• expected that guanidine–bisurea bifunctional organocatalyst 1 would be effective in promoting α-amination of β-keto esters as a result of interactions between guanidine and enolate of the β-keto ester, and between urea and azodicarboxylate (Figure 1b). Herein, we describe the catalytic asymmetric α

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• [26]. The now familiar glycoluril motif of 16 clearly has the rigid C-shaped required, and a subsequent report showed it to be capable of complexing dihydroxybenzenes using a combination of aromatic stacking and hydrogen bonding to the urea carbonyl groups [27]. The aromatic stacking surface can be

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• trimers as shown by Lincoln et al. [77].) The longer succinamide linker in 66β-CD2su engenders higher viscosities than does the shorter urea linker in 66β-CD2ur probably because steric hindrance between the adjacent adamantyl-substituted poly(acrylate) chains is greater when 66β-CD2ur forms a cross-link

• [76]. (The 66 prefix in 66β-CD2su and 66β-CD2ur indicates that the succinamide and urea linkers are attached to the C6 carbon in a D-glucopyranose subunit of each β-CD.) The increasing length of the adamantyl tether from amido to hexylamido in PAAAD and PAAADhn progressively decreases steric hindrance

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• already discussed [21][22][23], the bifunctional nature of organocatalysts plays an important role in this reaction to attain satisfactory levels of enantioselectivity. The presence of additional hydrogen donors such as urea groups positively affected the enantioselectivity both in the presence of chiral

• base organo-catalysts and when using quaternary ammonium salts. In the latter case, however, only 46% ee was obtained using the bifunctional urea-containing ammonium salt catalyst introduced by Dixon's group [30]. Readily available commonly used quaternary ammonium salt catalysts gave racemic mixtures

• the urea and ammonium sides of the catalyst (Table 1, entries 16, 17, and 21). Electron-neutral or bulky aryl groups on the ammonium side, as well as the introduction of a naphthyl group, did not result in any improvement of the enantioselectivity. Also, the presence of aliphatic groups on the urea

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• [4]arenes are sulfur-bridged analogs of calix[4]arenes, which have potential application in the molecular recognition of cationic, anionic or neutral molecules. In this regard, Yamato et al. incorporated two urea moieties possessing various aryl groups and two pyrene-appended triazole rings at the

• opposite side of the thiacalix[4]arene cavity [38]. The authors found that receptor 52 (Scheme 18) could selectively bind Cl− through hydrogen bonding interaction with the urea NH protons, and 52 can also bind with Ag+ through complexation with the pyrene-appended bistriazole. In homogeneous catalysis

Urethane tetrathiafulvalene derivatives: synthesis, self-assembly and electrochemical properties

• Xiang Sun,
• Guoqiao Lai,
• Zhifang Li,
• Yuwen Ma,
• Xiao Yuan,
• Yongjia Shen and
• Chengyun Wang

Beilstein J. Org. Chem. 2015, 11, 2343–2349, doi:10.3762/bjoc.11.255

• intermolecular interactions in molecular self-assembly systems. Therefore, molecules containing urea, amide and other similar groups have been investigated because these molecules can easily generate intermolecular hydrogen bonds [7][8][9]. Tetrathiafulvalene (TTF) derivatives have been widely investigated in

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• existence of life. It is also present in many small molecules acting as an intramolecular configurational lock. This is realized in hydrazones [1], heterocyclic urea derivatives [2], molecules exhibiting photoexcited proton transfer [3] and other compounds [4][5][6] reported also by us [7][8][9][10]. The

• studied by MS [44] while its interaction preferences with anions in solution are not known. On the other hand the tris-urea derivatives with a spacer between NHCONH groups were used in several supramolecular complexes including those with encapsulated anions [45][46], sensing nerve agents [47] or in self

• other hand understanding the behaviour of non-rigid molecules may also be useful and a challenging task. Experimental Synthesis Compound 1 was obtained by heating urea (1.0 g, 16.7 mmol) and n-butyl isocyanate (3.3 g, 33.4 mmol, 1:2 molar ratio) for 24 h under reflux in pyridine (20 mL). Then pyridine

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• ], one of the greatest physical organic chemists in China, my small group survived until I returned to the institute. I was so impressed by the work of Professor Zimmerman on the folding of linear urea derivatives driven by intramolecular hydrogen bonding [21], that in 2001, our group started several

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• described for nagelamide B (8) [15]. The structure of citrinamine C (3) was elucidated to be the 2,2´-didebromo derivative of nagelamide B (8) with an additional methylation of the hydroxy group at C-9 (80.8 ppm) and an oxidation of the imidazole ring at position C-13 (154.6 ppm) (an urea instead of a

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• heterocyclic compounds with cyclic urea core, are widely used as intermediates in industrial production of α-amino acids [1]. They exhibit various biological activities making them attractive candidates for drug discovery [2][3][4][5][6][7][8][9][10][11]. In the most cases, the observed biological activities

Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides rather than ynamides

• Armando Navarro-Vázquez

Beilstein J. Org. Chem. 2015, 11, 1441–1446, doi:10.3762/bjoc.11.156

• for the corresponding isomers for a selected combination of starting amides or carbamates and a final urea example (Figure 1) were computed using ab initio and DFT methods. Results and Discussion Computational procedures It is known that ab initio prediction of cumulene–polyynes isomerization energies

• position. A final and more demanding test is the Hsung observation that whereas only ynamide 12 was observed upon isomerization of the corresponding N-propargylamide, the related carbamate 13 only evolves to the allenamide stage [18]. Furthermore, urea 14 (see page 5069 of [3], we thank one of the referees

• for highlighting this example) again furnished only the ynamide compound. The ωB97 computations predict the ynamide 12c to be more stable than allenamide 12b by 1.7 kcal/mol (Table 2). On the other hand, the yncarbamate 13c is nearly degenerate with the allencarbamate 13b. For the urea 14 this trend

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• ]. Even so, industrial processes using CO2 as chemical feedstock are limited to the production of few large scale chemicals such as urea, methanol, salicylic acid as well as inorganic and organic carbonates [5]. Since CO2 is captured in huge amounts from the flue gases of fossil fuel combustion, it would