Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• noting that the developed protocol could be easily applied to the synthesis of anilines and aryl thiols. In 2014, the Jiang and Han group used a copper-doped graphitic carbon nitride catalyst Cu-g-C3N4, which was prepared from urea and CuNO3, and developed a ligand free protocol for the synthesis of

• directing groups including azo, amide, anilide, carbamate and unsymmetrical urea, could also promote the ortho-hydroxylation of arenes. Remarkably, 1,4-dioxane not only served as the solvent, but also played an indispensable role in the oxidation of the palladium complex by generating hydroxyl radicals

Adsorption of RNA on mineral surfaces and mineral precipitates

• Elisa Biondi,
• Yoshihiro Furukawa,
• Jun Kawai and
• Steven A. Benner

Beilstein J. Org. Chem. 2017, 13, 393–404, doi:10.3762/bjoc.13.42

• % formamide gel loading buffer for denaturing PAGE analysis (18%, 7 M urea). Gels were dried for 30 min at 80 °C before being exposed to a phosphorimager screen for quantitative autoradiography. Mineral identification with X-ray powder diffraction Identification of synthetic minerals was conducted with a

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• , Steinhof et al. [47] studied the equilibria and kinetics of the reaction of 1,3-dimethylurea with formaldehyde, which is a model for the industrially relevant urea–formaldehyde system. The reaction was performed in a batch reactor and the analysis was carried out using a commercial NMR flow probe (Figure

•  10). The design represented in Figure 10 allows the regulation of the molar ratio of reagents for the kinetic experiments (urea/formaldehyde from 1:1 to 4:1) as well as the temperature and pH, which were constantly measured. The reaction mixture flowed to the NMR instrument (400 MHz) by way of a pump

A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

• Wangkhem P. Singh and
• Rajkumar S. Singh

Beilstein J. Org. Chem. 2017, 13, 138–149, doi:10.3762/bjoc.13.17

• coordination, ionic, hydrophobic forces, etc.) into the gelator molecular structure and studying their gelation behaviour. H-bonding interaction (present in amide, urea, carbamate linkages, etc) alone or in combination with other interactions is the most extensively used strategy in the design of gelators [23

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• , hence both reactions will be described in detail. The Biginelli reaction The Biginelli reaction is a three-component reaction between an aldehyde (in many cases aromatic aldehydes give much better results than aliphatic ones), a β-keto ester (α-acidic compound) and urea or thiourea (some mono N

• , aldehyde 1 is activated by a Lewis- or a Brønsted acid. In the next step, urea/thiourea 2 can serve as a nucleophile and react with the activated carbonyl carbon to form a heminal species. However, under acidic conditions heminals can eliminate water and form an N-acyliminium cation 3. This reactive cation

• mechanism was supported by spectroscopic data. However, alternative mechanisms are discussed in the literature [17][18]. In the so called enamine route, urea 2 and the β-ketoester 4 form an enamine in the first reaction step. Subsequently, the enamine reacts with the aldehyde 1 [19]. A third mechanism

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• here that the crude mixture was cleaner in comparison with dry-grinding conditions. Indeed, the symmetrical urea of the starting amino ester – obtained from the corresponding N-carbamoyl imidazole amino ester A – was not observed, as shown by the LC–MS analyses of the crude mixture. An approach

Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

• Davide Brenna,
• Elisabetta Massolo,
• Alessandra Puglisi,
• Sergio Rossi,
• Giuseppe Celentano,
• Maurizio Benaglia and
• Vito Capriati

Beilstein J. Org. Chem. 2016, 12, 2620–2626, doi:10.3762/bjoc.12.258

• performed in continuo (Scheme 2). In the case of 4-nitrobenzaldeyde, the use of DES B (a ternary mixture of ChCl, urea and water, 1:2:1.5 ratio) led to impressive results, both in reaction rate and stereoselectivity, compared to the reaction run in DES A (Table 4, entries 1–4). The reaction proceeded

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• found that the bicyclic vinylogous urea 9d (64%) required a more careful flash chromatographic separation [19]. Unfortunately, the bicyclic vinylogous amide 9a could not be separated adequately from the triphenylphosphine residues under standard chromatographic and recrystallisation conditions. In an

• or partially reduced. In the case of the reduction of 9a, which still had significant triphenylphosphine residues present, we were unable to isolate any product. Interestingly, we were also never able to isolate the reduced product 12d when the bicyclic vinylogous urea 9d contained anything more than

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• traditional way this heterocycle is synthesized from urea, aldehydes, and 1,3-diketones. The method described in this work is quite general and can be applied to any monocyclic structure. The Supporting Information contains an atlas of target bond dissection maps applied to 27 kinds of heterocyclic structures

• 1,3-diketones, urea, and aldehydes. A full integer partitioning and target bond dissection mapping analysis for three-component couplings of this heterocycle, as shown in Figure 9, indicates that the chemical space consists of twelve [3 + 2 + 1], six [4 + 1 + 1], and two [2 + 2 + 2] possible

• ]. Scheme 11 shows the following literature examples of [3 + 2 + 1] cycloadditions following novel mappings (blue structures shown in Figure 9): Dabiri [189][190], and Singh [191]. The Yi [192] example follows the traditional coupling using a nitrile instead of a urea precursor, which ultimately leads to a

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• Minosaminomycin by Kondo et al.: The only total synthesis of minosaminomycin (9) to date was reported in 1977 by Kondo et al. (Scheme 14) [69]. Enduracididine (1) was prepared using the method reported by Shiba et al. [54] and was coupled with the isocyanate formed in situ from protected leucine 74 affording urea

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• /bjoc.12.222 Abstract A dipeptide-based urea-amide tertiary amine (DP-UAA) was shown to be an effective Brønsted base catalyst for the first asymmetric annulation reaction between 5H-thiazol-4-ones and N-itaconimides. High levels of enantioselectivity (up to 99% ee) and diastereoselectivity (>19:1 dr

• chemoselectivity and thus the moderate yield. When the H-bond donor was changed from thiourea to urea (catalyst II), it did not provide better results (Table 1, entry 2) [17][19]. In the [4 + 2] annulation of 5H-thiazol-4-ones with nitroalkenes, dipeptide-based thiourea−amide−tertiary amine III (DP-TAA) was

• dipeptide-based tertiary amine for this type of reaction. By modifying the thiourea moiety of III to urea lead us to catalyst DP-UAA IV, which could further increase the enantioselectivity (Table 1, entry 4). Subsequently, we screened the solvent effect with IV as the catalyst (Table 1, entries 5–7), and

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• ]. Some urea and thiourea derivatives have been studied as CNS agents [7] and anthelmintic drugs [8]. This heterocyclic core therefore represents the foundation for potential bioactive agents. A few methods have been described for the synthesis of 2-iminoazacycloalkanes from acyclic precursors. One

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

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