N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• aldehydes and hydrogen-bond activation of nitroalkenes. Keywords: asymmetric organocatalysis; hydrogen bond; Michael addition; pyrrolidine; thiourea; urea; Introduction Asymmetric organocatalysis became one of the strategic ways for the efficient synthesis of chiral compounds [1]. Bifunctional catalysis

• successful applications of sulfinylureas and thioureas as organocatalysts, we have designed four new N-sulfinyl-N’-(pyrrolidinylmethyl)urea and N-sulfinyl-N’-(pyrrolidinylmethyl)thiourea bifunctional organocatalysts. The main design principles are outlined in Figure 1. The catalysts feature a pyrrolidine

• unit, which should engage in enamine activation of enolizable carbonyl compounds. The urea or thiourea moiety shall provide hydrogen-bond donating ability. Furthermore, these compounds possess a sulfinyl group with an additional stereogenic center on the sulfur. To verify the influence of a matched

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• bonding moieties are either urea-based or peptide-based (i.e., phenylalanine) units, the dodecyl chains act as hydrophobic shields to induce the amphiphilic assembly in water and prevent the surrounding water from interfering with the hydrogen bonds in the interior [29]. Attaching a hydrophilic PEO chain

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• , the reactions were carried out under base-free conditions. It was found that urea-based catalysts outperformed squaramide derivatives, and that the installation of a chlorine atom adjacent to the catalyst’s quinoline moiety aided in avoiding selectivity-reducing complications related to the production

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• receptors have often proven more efficient [9][12]. A breakthrough in the field of anion binding towards its application in catalysis was achieved with the findings that neutral (thio)urea derivatives are potent anion receptors due to their ability to bind anions of various topologies, including the

• spherical halides [10]. The key to hydrogen bonding of the halide anion resides in the polarized N–H bonds of these (thio)urea units, which have since served as a benchmark in the design and development of anion receptor catalysts [12][13][14]. Consequently, other synthetic anion receptors have been

• between the catalyst and the substrate, which exclusively stabilize the transition state that forms the major enantiomer. Furthermore, Gouverneur and co-workers established an enantioselective nucleophilic fluorination protocol using a chiral bis-urea catalyst 41 and CsF as an inorganic fluoride source

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• them ideal ASO modifications as only a limited number of modifications is needed for a substantial effect. Recently, a versatile method of post-ON synthesis conjugation, different from the click chemistry method, has been applied to 2’-amino-LNA. A class of 2’-urea-LNA analogues (58–62) has been

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• presence of strong aqueous acids (>1 M) or alkali (>1 M), is required to observe an appreciable degradation accompanied in many cases by urea or biuret as the hydrolysis products. The compounds are also relatively resistant to many classical reducing and oxidizing agents [2]. However, very strong oxidants

• such as lead tetraacetate, potassium permanganate, or refluxing hydrogen peroxide were shown to produce urea-derived degradation products [3]. Biguanides also possess a remarkable capability to form stable metal complexes, a property that was already noticed by B. Rathke in 1879 [4]. Indeed, he relied

• cyanoguanidines, dicyanamides, carbamide or N1-cyano-S-methylisothioureas and the addition of guanidines to carbodiimides, cyanamides or (iso)(thio)urea derivatives. Synthesis from amines Addition of amines to cyanoguanidines (pathway a) Reaction of amines with cyanoguanidine: The use of cyanoguanidine as the

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• construction of dihydropyrimidinones 78 utilizing a three-component reaction of acyclic 1,3-diketones 54, urea/thiourea (77) and aldehyde 5 exploring La2O3 as catalyst under microwave irradiation under solvent-free conditions with good functional group tolerance and excellent yields (Scheme 28). The reaction

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• . Consequently, we decided to develop a new synthetic strategy for the preparation of trigonoine B (1). Carbodiimides are valuable synthetic intermediates that can be obtained by an aza-Wittig reaction of isocyanates with iminophosphoranes or by dehydration of urea [26]. Molina et al. previously reported the

• -azahexatriene system. Lastly, it was proposed that the carbodiimide 10 could be derived from urea 11. Therefore, we investigated the electrocyclization of a pyrrol-3-ylbenzene containing a carbodiimide moiety. First, 2-(pyrrol-3-yl)aniline 14 was synthesized by a Suzuki–Miyaura coupling reaction of 2

• , affording aniline 15 in 65% yield. Treatment of 15 with phenyl isocyanate in CH2Cl2 gave urea 16a in 54% yield. To obtain carbodiimide 17a, 16a was treated with carbon tetrabromide (CBr4), PPh3, and Et3N in CH2Cl2. The reaction was monitored by TLC, which confirmed the complete consumption of the starting

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• building blocks for the construction of more elaborate structures [7][8][9][10][11]. An outstanding class of quinine derived organocatalysts exhibits a bifunctional mode of activation by the incorporation of an acidic unit, such as urea, thiourea, squaramide or sulfonamide moieties, giving rise to the

• organocatalysts 8d and 9a,b in the literature [30][41]. Among the 11 screened organocatalysts, the ones with amino-substituted DMAP cores gave unimpressive ee values (Table 1, entries 2–5). The quinine-derived organocatalysts 8a–d failed to attain striking stereoselectivity (25–43% ee). The popular urea–quinine

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• rearranged within a residence time of 30 minutes rendering the corresponding carbamates 3a–e in high chemical yields. Phenylacetic acid species were found to be less reactive substrates that rearranged more slowly (tRes = 60 min) and thus giving lower yields (3f–h). Moreover, the formation of urea side

• interesting case concerned the use of 3-oxocyclobutanecarboxylic acid (1m), which yielded the desired carbamate product 3m along with the carbamoyl-urea species 3m’. This observation parallels recent reports [25] proposing a fragmentation of the desired carbamate followed by a combination of the resulting

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• pyrrolizidines; cyanoketones; legonmycin; vinylogous ureas; Introduction At least 40 members of the large class of pyrrolizidine alkaloids [1][2][3][4] have so far been characterized from bacterial cultures. Of these ‘bacterial pyrrolizidines’, those of the vinylogous urea type are particularly intriguing from

• various C(7a)-hydroxylated bacterial pyrrolizidines including the legonmycins, jenamidines B and C, and bohemamine D (cf. [26][27][28][29][30]). With all this in mind, we set out to develop a simplification of Snider’s route [14][15] to the vinylogous urea core for application to the synthesis of

• . The clazamycins, and selected bacterial pyrrolizidines of the vinylogous urea type. For consistency, the standard numbering convention used for the plant pyrrolizidines, as depicted for the clazamycins, is used throughout. Key species in the biosynthesis of legonmycins A (3) and B (4), and the

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• several properties of a specifically 3-FTyr-labelled α-synuclein analogue, including its native conformation and the conformational changes induced by urea, spermine and sodium dodecyl sulfate (SDS) [75]. Subsequently, α-synuclein interaction with SDS micelles and model membranes have also been

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• recognition ability can be further strengthened by the introduction of another chiral moiety directly onto the urea N atoms. The systems with double chiral units being located around the binding ureido cavity showed better stereodiscrimination, with the highest selectivity factor being 3.33 (KL/KD) achieved

• . The shapes and geometries of anions are widely different, and therefore the design of corresponding tailor-made receptors is based mostly on more directional interactions, such as hydrogen bonds. Indeed, an incredible number of neutral receptors bearing amide, sulfonamide, urea, thiourea, pyrrole, or

• highly sophisticated molecules, including anionic receptors [27][28][29][30][31][32][33][34][35][36][37][38][39]. During our ongoing research on anion complexation, we have reported various calix[4]arene receptors based mainly on amide, urea, or thiourea groups [40][41], some of which are available in

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• synthesizing isoquinoline derivatives using LSA-FAS-Cu as catalyst was investigated. As shown in Table 6, LS-FAS-Cu could promote 2-(phenylethynyl)benzaldehyde (11a) and urea (12a) to generate 3-phenylisoquinoline (13a) in excellent yield, while the referential catalysts showed inferior catalytic activity

• acetophenones and 1,3-diaminopropane to synthesis 2‑arylpyridine derivatives.a Acid density of catalyst. Substrate scope of the ketones catalyzed by LSA-FAS-Cu. LS-FAS-Cu catalyzed synthesis of aminonaphthalene derivatives.a Synthesis of the 3-phenylisoquinoline from 11a and urea (12a).a Supporting Information

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• ) at 65 °C for 15 min. They were purified using denaturing polyacrylamide gel electrophoresis (gel solution: 7 M urea, 1 TBE buffer, 14 or 18% (depending on the length of the oligonucleotide) polyacrylamide/bisacrylamide (29:1); loading buffer: 11.8 M urea, 42 mM Tris·HCl (pH 7.5), 0.83 mM EDTA (pH 8.0

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• source of nitrogen has also been varied from the classical use of ammonia. The most common nitrogen source reported in literature is ammonium acetate (3). Others include the use of oxahydrazines, primary amines, and urea. The oxidation of dihydropyridines to pyridines has been achieved using mild

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• bis(carbazolyl)urea-derived receptor allowed the sensitive detection of diphosphate in water by surface plasmon resonance (SPR) [29]. Silica nanoparticles containing a dye coordinated to a bis(zinc(II)–DPA) receptor released the dye upon diphosphate binding [30], and thus producing an optical signal

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• enantioselectivities (20 examples, up to >99:1 er), with a quantum yield of 0.013. While there has been significant progress using bifunctional catalysts, dual catalytic systems can offer other modes of reactivity. For instance, Jiang et al. developed a urea-catalysed formal arylation of benzofuranones 215, using

• "Brønsted acid catalysis", yet interestingly their conjugate bases can also be used as efficient hydrogen bonding catalysts. Knowles et al. showed that a tricatalytic system using chiral phosphate 235 can mediate the deracemisation of cyclic urea rac-236 (Scheme 36) [97]. The proposed mechanism involves a

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• imidazole (32–98% yield) and pyrimidine derivatives (45–88% yield), with a broad substrate scope, when using deep eutectic solvents [choline chloride (ChCl)/glycerol (1:2 mol/mol) and ChCl/urea (1:2 mol/mol)] as environmentally benign and non-innocent reaction media, by modulating the temperature (25 or 80

• material only (conversion: 81%, Table 2, entry 1). The employment of ChCl/urea (1:2 mol/mol) as the eutectic mixture provided 7a in 57% yield and 3a/3a' in 43% yield, but with full conversion (Table 2, entry 2). By lowering the equivalents of Et3N up to 1, or alternatively using K2CO3 (3 equiv) as a base

• , in ChCl/urea, the yield of 7a dropped down up to 33% and that of 3a/3a' up to 25% (Table 2, entries 3–5). By changing the solvent to pure Gly, 7a and 3a/3a' now formed in 52 and 37% yield, respectively (Table 2, entry 6). When Et3N (3 equiv) was alternatively used as the sole solvent, the formation

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• example, a carbazole-urea macrocycle was reported previously [10], however, the binding of anions occurred outside the receptor due to modest dimensions of the macrocyclic cavity. Using click-chemistry, a carbazole-triazole macrocycle, “tricarb”, was prepared that showed the ability to form non-covalent

• carboxylates were modelled computationally using COSMO-RS. Several observations were made from the computational structures. Intramolecular hydrogen bonds between the urea carbonyl and the carbazole NH protons were present in macrocycles MC001 and MC003, as indicated in Figure 4. The rings of these macrocycles

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• performed by using the model substrates benzaldehyde (2a, 1.0 mmol), ethyl acetoacetate (4, 1.0 mmol), and urea (5, 1.0 mmol) in H2O (3.0 mL) in the absence of a catalyst under ultrasound irradiation at 45–50 °C for 60 min. It was observed that the reaction proceeded with a very low yield (20%) of product

• . The obtained results are summarized in Table 6. Benzaldehyde (2a) underwent the reaction with ethyl acetoacetate (4) and urea (5) to obtain the corresponding dihydropyrimidinone 7a in 97% yield (Table 6, entry 1). Benzaldehyde derivatives bearing electron-donating groups, such as 4-Me (2b), 4-OMe (2e

• ), 3,4-dimethoxy (2f), 3-OH (2r), and 2-OH (2h), respectively, at different positions on the ring reacted well with ethyl acetoacetate (4) and urea (5) to produce the products, 7b–f in good isolated yields that ranged from 92–96% (Table 6, entries 2–6). A benzaldehyde derivative with an electron

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• DHPMs becomes an urgent and paramount task. In connection with this, multicomponent Biginelli and Biginelli-like reactions of aldehydes, urea/thiourea, and enolizable carbonyls revealed as very efficient tools to prepare DHPMs [3]. Although the Biginelli reaction was firstly discovered over a century

• ago [10], little attention was given to asymmetric pathways. Only in 2003, Juaristi and Muñoz-Muñiz have reported the reaction of benzaldehyde, urea, and methyl acetoacetate using a chiral amide with CeCl3 for the first time. However, only 40% enantiomeric excess (ee) was obtained [11]. Then, Zhu

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• chemistry demands. Several methods were reported for the synthesis of triazinethione analogs. One of the most popular methods involved the reaction of a carboximidamide [16], or urea [17] with isothiocyanates. The C=S bond in the latter is highly polar, with the carbon atom always positive and therefore

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• of activated carbons is possible at the precursor stage or as a modification step after the production of activated carbons and results mostly in a basic character of the prepared materials. Typical nitrogen agents are ammonia, urea or amines. Different types of nitrogen-containing functional groups

• found by ammoxidation of demineralized coal in the last preparation step after carbonization and activation [10]. Hu and coworkers synthesized nitrogen-doped carbon materials from coconut shell by urea modification and K2CO3 activation. The carbonized precursor is mixed with urea (1:1 weight ratio

• ), heated and the unreacted urea is removed by a washing step with hot water. Subsequently, the urea-treated samples were activated. The treatment with urea enhanced significantly the nitrogen content in the samples, while the final amount of nitrogen was reduced by the activation step [63][113]. Activated