1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• quinoid type to study their photophysical properties in solution and in the solid-state, Ooyama and co-workers [106] studied a synthetic route for the preparation of compounds with the tricyclic benzo[c]carbazol-6-one skeleton. The strategy used was through the reaction to β-NQS 18 with a bifunctional

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• Jiang-Song Zhai Da-Ming Du School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No.5 Zhongguancun South Street, Beijing 100081, People’s Republic of China 10.3762/bjoc.18.3 Abstract Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2

• conveniently and comprehensively. However, as we know, the construction of these compounds is mostly carried out through transition-metal-catalyzed cyclization reactions [11][12][13][14], whereas strategies using bifunctional chiral thiourea catalysts are rarely reported. In 2018, Du's group reported a novel

• bifunctional thiourea catalyst, a series of target products in excellent yields with excellent stereoselectivities can be obtained under mild conditions in this reaction. Notably, this protocol provides direct access to indanone-derived spirobarbiturates, which are difficult to access with other methods

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• great potential for catalysis of a wide range of reactions to achieve good to perfect enantioselectivities. This is due to their ability to act as synergistic bifunctional catalysts bearing both Brønsted acidic and Lewis basic sites, with the 3,3′-substituents playing a crucial role in achieving

• ring [36]. Experiments showed that chiral phosphoric acid CPA 2 acted as a bifunctional organocatalyst, that activates 2-naphthols and quinone derivatives via multiple H-bonds and promotes the first step of the enantioselective conjugative addition to generate intermediate I-1 and transfers the its

• 2019, Li and co-workers developed a synthetic strategy for the atroposelective construction of phenylindole 20 by the chiral phosphoric acid-catalyzed cross-coupling of quinones 18 and indoles 19. In this reaction, the chiral phosphoric acid (R)-CPA 6 acts as a bifunctional catalyst to activate indoles

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• -unsaturated carbonyl compounds catalyzed by bifunctional squaramide catalysts has been developed. This methodology offers both enantiomers of β-silyl nitroalkanes in good to excellent yields (up to 92%) and enantioselectivities (up to 97.5% ee) under solvent-free conditions at room temperature. Control

• even with better yields while the enantiomeric excess was unperturbed. Conclusion In summary, we have outlined bifunctional squaramide-catalyzed 1,4-conjugate addition reaction of nitromethane to β-silyl α,β-unsaturated carbonyl compounds to access a series of chiral β-silyl nitroalkanes in high yields

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

• , Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia 10.3762/bjoc.17.176 Abstract The synthesis of bifunctional N-sulfinylureas and thioureas with an appended pyrrolidine unit is presented. These organocatalysts were evaluated in

• 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

• -sulfinylurea as bifunctional organocatalyst [23]. The enantio- and diastereoselective addition of Meldrum’s acids to nitroalkenes via N-sulfinylurea catalysis gave products that were readily converted to pharmaceutically relevant compounds [24][25]. A sulfinylurea organocatalyst catalyzed a highly selective

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• asymmetric aza-MR. Thus, the review includes the examples wherein cinchona alkaloids, squaramides, chiral amines, phase-transfer catalysts and chiral bifunctional thioureas have been used, which activate the substrates through hydrogen bond formation. Most of these reactions are accompanied by high yields

• derivatives, phase-transfer catalysts and bifunctional thiourea derivatives. 1.1 Reactions catalyzed by chiral cinchona alkaloid derivatives Cai et al. prepared and used a number of organocatalysts from Cinchona alkaloids for the aza-MR of aniline (1) with chalcone (2) to obtain the adducts 4 in poor to very

• reactions [34][35]. In 2015, Zhao et al. synthesized spiro[pyrrolidine-3,3'-oxindoles] 29 in single step by asymmetric cascade aza-Michael/Michael addition reaction between 4-tosylaminobut-2-enoates 27 and 3-ylideneoxindoles 26 catalyzed by a chiral bifunctional tertiary amine, squaramide (cat. 28) which

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

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

• example utilizing this strategy was provided by Jacobsen and co-workers for the desymmetrization of meso-aziridines 29. In their work, the bifunctional phosphinothiourea catalyst 31 promoted the C–N bond cleavage by hydrochloric acid upon initial protonation (Scheme 7) [55]. Subsequently, the catalyst

• catalysts’ designs Basic/nucleophilic – H-donor bifunctional catalysts: Over the past decades, chiral bifunctional catalysts bearing a thiourea as HB-donor and a basic or nucleophilic group such as an amine have emerged as a powerful tool in organocatalysis by assisting to enhance the catalyst performance

• the previous sections. For example, catalyst 25 bearing a nucleophilic aminoalcohol functionality interacts with the boronic acid reagent in the Reissert-type reaction with acylated quinolines (Scheme 5b) [36], while the phosphine moiety in the bifunctional phosphinothiourea catalyst 31 allows for

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• -bifunctional organomagnesium alkoxide reagent 107, which converted esters into di- and monofunctionalized anthracenes (Scheme 25) [59]. They prepared this reagent by deprotonation–magnesiation of compound 106. Then, the treatment of aromatic esters with 107 produced dialkoxide 108, which could be easily

• anthracenes from a bifunctional organomagnesium alkoxide. Palladium-catalyzed tandem C–H activation/bis-cyclization of propargylic carbonates. Ruthenium-catalyzed C–H arylation of acetophenone derivatives with arenediboronates. Pd-catalyzed intramolecular cyclization of (Z,Z)-p-styrylstilbene derivatives

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• ammonium salts derived from cinchona alkaloids [28]. Therefore, the asymmetric synthesis of coumarin derivatives is herein presented according to the activation mode, i.e., via covalent or non-covalent bonding. Furthermore, the use of bifunctional catalysts and multicatalysis are discussed as well

• addition of 4-hydroxycoumarin (1) by the Re face of the enones 2 through a bifunctional modified binaphthyl organocatalyst 18 with primary amine [37]. The reaction occurs through the activation of the enone substrate by formation of an iminium ion intermediate and, in the presence of an acid additive

• discussed above, the organocatalysts may also proceed by noncovalent activation, in which a hydrogen bond or an ion pair is formed. A broad variety of mono- and bifunctional chiral hydrogen-bonding organocatalysts has been developed, in special using cinchona alkaloid derivatives [52]. In this sense, Lin

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• reported. A bifunctional thiourea catalyst was found to be effective for this reaction. With 10 mol % of the catalyst, good results were attained for a variety of 1,5-dihydro-2H-pyrrol-2-ones under mild reaction conditions. Keywords: acyl transfer; enantioselectivity; Michael reaction; organocatalysis

• presence of the quinine-derived bifunctional squaramide catalyst I in dichloromethane at room temperature (Table 1). Delightfully, after stirring for 12 hours, a product was isolated in 70% yield that was characterized as compound 3a and was supposed to be formed through conjugate addition followed by

• benzoyl-transfer reaction. However, only 20% enantiomeric excess was achieved. Then, the tert-leucine-derived squaramide catalyst II was employed and here both yield and ee slightly improved. Next, we turned our attention to bifunctional thiourea catalysts [26][27] that proved to be fruitful. Thus, the

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

• interaction with the reagents. As a result, several hollow fibres-immobilised catalysts have been prepared and applied in flow scenarios [112]. A titania-, zirconia- and silica-implanted polyamide-imide (PAI) hollow fibre was grafted with aminosilane functional groups in order to create a bifunctional

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• [32] found a bifunctional group reaction of perfluoroalkylation and β-alkenylation by a perfluoroalkyl radical. Perfluoroalkylation product 93 was synthesized by utilizing (E)-3-methyl-1-phenylhept-1,6-dien-3-ol (92) and perfluorobutyl iodide (28) as substrates and potassium phosphate and DABCO as

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

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

• respect, a bifunctional quinine-derived sulfonamide organocatalyst was developed to catalyze the asymmetric sulfa-Michael reaction of naphthalene-1-thiol with trans-chalcone derivatives. The target sulfa-Michael adducts were obtained with up to 96% ee under mild conditions and with a low (1 mol

• %) catalyst loading. Selected enantiomerically enriched sulfa-Michael addition products were subjected to oxidation to obtain the corresponding sulfones. Keywords: asymmetric synthesis; bifunctional catalysis; cinchona alkaloids; organocatalysis; sulfa-Michael reaction; Introduction Derivatives of the

• 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

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• , such as pipecolic acid [66]. In E. coli, the catabolism of proline occurs via the action of the bifunctional enzyme putA (Figure 9B) [67]. It sequentially degrades proline to glutamate, which can be later deaminated to an essential metabolite, α-ketoglutarate, with many metabolic options, such as an

• some therapeutic dehydrogenase inhibition schemes [71]. Conversely, there is strong evidence that other proline analogues, dehydroproline and thiaproline, are oxidatively degraded in E. coli by the action of the bifunctional enzyme putA and the reductase proC [72]. Future research should examine

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• ring seems promising since β-diketones as well as o-quinones are known as chelating ligands. The combination of two different chelating sites in the same molecule should give a bifunctional bridging ligand. Such species are interesting from the viewpoint of assembling of ordered structures in a crystal

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• isoindigo 100 was used as substrate, enantioselective [3 + 2] annulation with allene 101 in the presence of amino acid-derived bifunctional phosphine 102 produced adduct 103 in 90% yield with 92% ee and 4:1 regioisomeric ratio (rr). The authors suggested that the observed regioselectivity could be

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• . If a signal broadens beyond detection and thus disappears from the spectrum, be it due to aggregation or intermediate exchange kinetics, it is also impossible to trace its trajectory and determine the chemical shift perturbation. In the case of a bifunctional GCP ligand binding to survivin [46], the

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

• different approaches have been developed that use a single catalyst. Alemán et al.’s approach combines the two catalytic motifs into a single bifunctional catalyst 38, using thioxanthone as the chromophore (Scheme 5) [31]. The catalyst 38 was then applied to known reactions such as the α-functionalization

• that is trapped intermolecularly by N-hydroxycarbamates 152 (Scheme 21b) [71]. Bach et al. has recently reported a bifunctional catalyst 154, which contains both a photoactive thioxanthone unit and a CPA (Scheme 22) [72]. They have applied this photocatalyst to the [2 + 2] photocycloaddition of

• :33 rr) but this example does demonstrate an interesting proof of concept with potential for the development of processes using alternative bifunctional catalysts. Phase-transfer catalysis Phase-transfer catalysis (PTC) is another non-covalent mode of catalysis that has been combined with

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• targets for new antitubercular drug developments [6]. Mycobacterial galactan is synthesized by two bifunctional galactofuranosyltransferases, GlfT1 and GlfT2 (Supporting Information File 1, Figure S1). The former one initiates the galactan biosynthesis by addition of the first two Galf residues to

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• , if both the nucleophile and the electrophile are activated independently by distinct functional groups on the same catalyst, this is referred to as bifunctional catalysis (Figure 2, (1)) [48]. When the two catalysts work in a cooperative way to activate only one substrate, this is classified as

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• first run was observed. A sustainable method for the isosorbide production from cellulose is the use of a bifunctional catalyst (Scheme 7). A series of Ru catalysts on acid support were prepared by the adsorption of colloidal Ru nanoparticles on mesoporous and bulk niobium phosphate, mesoporous and bulk

• (5.0 wt % Ru, Ru nanoparticles (NPs): 0.9 nm) in 30 mL H2O after 1 h of reaction at 220 °C under 60 bar of H2. Trace amounts or even no isosorbide was obtained over microporous HZSM-5, NaY, and γ-Al2O3-supported Ru catalysts. A bifunctional Ru catalyst supported on mesoporous niobium phosphate with a

• . This study shows that a bifunctional catalyst can be a more sustainable solution to produce isosorbide from (ligno)cellulose. Conclusion The isosorbide synthesis from cellulose is performed via acid-catalyzed hydrolysis of cellulose, followed by hydrogenation of glucose to sorbitol and further

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• proceed via enamine intermediates (Figure 1B) [14][15][16][17][18][19]. The state of the art within this area has been recently demonstrated by Dixon and co-workers, who showed that bifunctional BIMP catalysts could promote the enantioselective addition of typically recalcitrant aryl ketones to