Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• both catalysts gave the Michael adduct in excellent yields, high ees were obtained only when 54b was used as organocatalyst (up to 94% ee, Scheme 16). During the last decade, squaramide catalysts have become a powerful alternative to the urea/thiourea and guanidine catalysts as multiple hydrogen bond

• through the enolate mechanism and complete noncovalent catalysis still needs further investigation. Biginelli reaction The catalysts 69f–j (Figure 8) were successfully applied to the enantioselective multicomponent Biginelli reaction of benzaldehyde, ethyl acetoacetate and urea [68]. The results show that

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• between heteroaryl bromides, chlorides or iodides and carbamate, sulfonamide or urea derivatives to be successfully realized in water using palladium-loaded TPGS-750-M (dl-α-tocopherol methoxypolyethylene glycol succinate) micelles (Scheme 1). Moreover, this micellar catalytic system allowed for catalyst

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• ) were solubilized in a total volume of 30 mL 20 mM Tris/HCl buffer, pH 8.0, containing 2 mM EDTA, 50 mM DTT and 8 M urea. After incubation on ice for 30 min, the solution was cleared by centrifugation (15 min at 15,000 rpm and 4 °C). The obtained supernatant was used as stock solution for the in vitro

• refolding. The PeAAOx was solubilized using 150 µg mL−1 protein in 20 mM Tris/HCl buffer, pH 9.0, containing 2.5 mM GSSG, 1 mM DTT, 0.02 mM FAD, 34% glycerol and 0.6 M urea at 4 °C for 80 h. After the incubation for PeAAOx activation/refolding, the refolding mixture was concentrated to 100 mL and the buffer

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• development of chiral bifunctional urea 1 [35], thiourea 2 and 3 [36][37], sulfonamide 4 [38][39][40] and squaramide 5 [38][39][40] catalysts derived from chloramphenicol base (Figure 1), which showed excellent reactivity and enantioselectivity for this asymmetric transformation. A typical example of the

• chloramphenicol-derived bifunctional amide organocatalysts and their application for enantioselective alcoholysis of meso-cyclic anhydrides. In the precedented urea- or thiourea-based organocatalytic methanolysis of anhydrides, one big problem is the homo-aggregation of the catalysts via hydrogen bonding, which

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• directly by fusion of thiourea/urea with 5-aminopyrazole 126 in an oil bath at 120 °C. N-Thiocarbamoyl pyrazole derivatives 180 and 183 underwent cyclization with hydrazine hydrate to give 5-(N-triazolyl)aminopyrazole derivative 182 and hydrazinopyrazolo[3,4-d]pyrimidines 185, respectively (Scheme 51). El

• -amines 198 possessing 4-(1H-benzimidazol-2-yl)phenylamine moiety at C4 position and primary as well as secondary amines at C6 position starting from 5-aminopyrazole-4-carboxamide (194). Compound 194 was treated with urea to give 1H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione (195) followed by chlorination

p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• ][54][55][56][57]. Modified macrocycles with the amide fragments at the lower rim can form complexes with the anions by hydrogen bonds of the amide group with the guest. It was shown that (thia)calix[4]arene derivatives with urea and thiourea fragments at the lower rim can bind anions through hydrogen

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• variations are adopted to improve the efficiency of this reaction for practical application towards drug discovery [126][127][128]. Modifications have been done in substrates by replacing urea with substituted ureas and thio urea, use of various 1,3-dicarbonyl compounds etc. Reactions using ionic liquids as

• give benzaldehydes and H+ under solvent-free mechanochemical conditions within 30 min. Further, addition of 1,3-dicarbonyl compounds and urea derivatives within the same milling jar led to the desired products in 78–95% yield at 3 h (Scheme 32). Benzaldehydes with electron-donating or -withdrawing

• groups, heteroaromatic aldehydes, N-methyl urea and thio urea also resulted in good to excellent yield with high regioselectivity. It is interesting to note that the reaction was irreproducible in the solution of ethyl acetate at room temperature even after 24 h [133]. A mechanochemical asymmetric three

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• ; thioureas; ureas; Introduction The urea molecule played the central role in the development of organic chemistry since its first documented synthesis in 1828 when the German chemist Friedrich Wöhler prepared it starting from ammonium cyanate (Scheme 1) [1]. This simple, yet intriguing transformation of an

• years, molecules with incorporated (thio)urea and guanidine subunits, due to their ability to coordinate other molecules and ions via N–H hydrogen bonding, have also been considered as organocatalysts and anion sensors [7][8][9][10][11][12]. In Scheme 2, several examples of (thio)urea- and guanidine

• isocyanate provided the target urea sensor after milling for 60 minutes at 18 Hz (Scheme 13a). Monitoring the progress of the reaction by ex situ 1H NMR spectroscopy in DMSO-d6 revealed that the reaction reached completion after only 30 minutes of ball milling with a conversion greater than 90%. Although the

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• combination with an anthracenylmethyl quaternary ammonium group (resulting in catalyst A2) allows them to carry out the syntheses of products 3 with high enantioselectivities [76]. Our group has over the last years been interested in the design and development of bifunctional (thio)urea/ammonium salt

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• understand and model these biological pathways, oxidative aromatization of 1,4-DHP to their corresponding pyridine derivatives has acclaimed wide attention. A variety of oxidants such as urea nitrate, BrCCl3/hν, nitric acid, nitric oxide, N-methyl-N-nitroso-p-toluenesulfonamide, DDQ etc. has been used to

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• Ryota Miyaji Yuuki Wada Akira Matsumoto Keisuke Asano Seijiro Matsubara Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo, Kyoto 615-8510, Japan 10.3762/bjoc.13.151 Abstract Bifunctional organocatalysts bearing amino and urea

• significantly contributed to the field of asymmetric synthesis [1][2][3][4][5][6]. In these catalysts, (thio)urea and tertiary amino functional groups cooperatively activate a nucleophile and an electrophile simultaneously, in a suitable spatial configuration. Thus, they enable various stereoselective addition

Detection of therapeutic radiation in three-dimensions

• John A. Adamovics

Beilstein J. Org. Chem. 2017, 13, 1325–1331, doi:10.3762/bjoc.13.129

• lab to create 3D images. Ionizing radiation reactions in the Fricke dosimeter. Sulfuric acid/urea promoted synthesis of LMG. Synthesized DTBs and their LMG (1) relative radiation dose sensitivity. Acknowledgements J. A. is grateful to the numerous students who have worked on this project and to Dr

Urea–hydrogen peroxide prompted the selective and controlled oxidation of thioglycosides into sulfoxides and sulfones

• Adesh Kumar Singh,
• Varsha Tiwari,
• Kunj Bihari Mishra,
• Surabhi Gupta and
• Jeyakumar Kandasamy

Beilstein J. Org. Chem. 2017, 13, 1139–1144, doi:10.3762/bjoc.13.113

• thioglycosides to corresponding glycosyl sulfoxides and sulfones is reported using urea–hydrogen peroxide (UHP). A wide range of glycosyl sulfoxides are selectively achieved using 1.5 equiv of UHP at 60 °C while corresponding sulfones are achieved using 2.5 equiv of UHP at 80 °C in acetic acid. Remarkably

• , oxidation susceptible olefin functional groups were found to be stable during the oxidation of sulfide. Keywords: monosaccharides; oxidation; sulfones; sulfoxides; thioglycosides; urea–hydrogen peroxide; Introduction Organosulfur compounds such as sulfides, sulfoxides and sulfones are useful intermediates

• [24]. Most of them are found to be stable which can be easily handled and stored. One such solid adduct is urea–hydrogen peroxide (UHP) which is considered to be a safer and efficient alternative to high concentrated aqueous hydrogen peroxide solution [25]. In addition, UHP is also commercially

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