CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• phenyl ring, the 3-trifluoromethylated compounds were obtained in 50–56% yields. However, coumarins bearing electron-withdrawing groups gave yields up to 70%. As for the mechanism, the trifluoromethyl radical was generated from CF3SO2Na and Mn(OAc)3, then CF3• added regioselectively onto the coumarin to

• -workers reported the synthesis of trifluoromethylated coumarin 71 and flavone 72 with CF3SO2Na (2 equiv), the hypervalent iodine F5-PIFA (pentafluorophenyliodine bis(trifluoroacetate)) (2 equiv) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 0.6 equiv). The trifluoromethylated compounds were obtained

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• led to the displacement of triphenylphosphine. Finally, coumarin derivatives 108 were obtained in yields of 40–90% as a result of intramolecular lactonization of the intermediate fumaric acid derivatives 107 [74]. In an analogous manner, but using 3-aminophenol, 7-aminocoumarin was obtained in a yield

• Gryko and Flamigni et al. for the preparation of 6-formylcoumarin derivatives 109 that are used in the synthesis of dyads 111 consisting of coumarin and corrole units (Scheme 61). The latter synthesis took place by condensation of formylcoumarins 109 with 5-(pentafluorophenyl)dipyrromethane (110) [76

• ylides in the intramolecular Wittig reaction. Synthesis of furan derivatives via resonance-stabilized ylides in the intramolecular Wittig reaction. Synthesis of 1,3-indanedione derivatives via resonance-stabilized ylides in the intermolecular Wittig reaction. Synthesis of coumarin derivatives via

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• [59] with coumarin 1 (Φfl = 0.73 in EtOH; λex = 380 nm) [46] as a reference. Photometric and fluorimetric pH titrations were performed in Britton–Robinson buffer (see above) solution (pH 2.0, c = 15 µM), and the pH value was adjusted by addition of NaOH (2 M). After each addition step, the pH and the

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

• target bond 3-partition dissection maps for 27 commonly found heterocyclic rings is given in the Supporting Information File 1 (see Schemes S6 to S32). These include benzimidazole, 2,3-dihydro-1H-benzo[b][1,4]diazepine, benzofuran, benzopyran, chromen-4-one, coumarin, cyclopent-2-enone, furan, Hantzsch

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

• contain two biologically important structural scaffolds, namely the 3-hydroxyoxindole and coumarin, which could be potentially used for further biological evaluation or serve as starting points in drug discovery pursuits. A highly stereoselective Mukaiyama–aldol reaction was reported by Zhou and co

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• cytotoxic activity. They can regularly be found in improperly stored food, hence, entering the food supply chain [6]. Further coumarin derivatives, e.g., umbelliferone (4), esculetin (5), and scopoletin (6), are subject of investigation due to their pharmacological properties, i.e., anticancer effects

• the coumarin derivatives umbelliferone (4, Figure 1), esculetin (5, Figure 1), and scopoletin (6, Figure 1) are subject of anticancer research [67]. Marmesin (62) was first isolated from the fruits of Ammi majus [67], and is currently under investigation as an agent for the treatment of angiogenesis

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• bioavailability of anticancer drugs. Thus, SuberAniloHydroxamic acid–cholesterol conjugates (SAHA–cholesterol) [11], cholesterol-based charged liposomes encaging doxorubicin [12] or curcumin [13] showed higher activity compared with the native drugs. Synthetic coumarin-caged cholesterol derivatives, for instance

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• (umbelliferone) (9) upon ring-closing metathesis. The synthesis of coumarin derivatives using this approach was described in previous publications [20][21]. By introducing an electron donor in the 7-position, a fluorescent product is obtained upon ring-closing metathesis [22]. Synthesis of the profluorescent

• (cooled at 5 °C to minimize evaporation) was pipetted. Then, 5 µL of a 3 mM precatalyst stock solution was added. Finally, 3 µL of the substrate stock solution was added (for the coumarin substrate 8 a 1 M stock solution was used, for the fluorophore quencher substrate 5, a 50 mM stock solution was used

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• prepared either in well water-soluble form or as gels of high swelling. Two versatile synthetic strategies for introducing a fluorescent tag (rhodamine, fluorescein, nitrobenzofuran or coumarin) into the water-soluble epichlorohydrin branched cyclodextrin polymers were worked out and compared. The

• techniques and capillary electrophoresis. The applied synthetic routes were evaluated based on the molecular weight, cyclodextrin content of the products and the efficiency of labeling. Keywords: coumarin; fluorescein; functionalized monomers and polymers; nitrobenzofurazan; rhodamine; Introduction

• , we report the controlled, regioselective fluorescent labeling of neutral and cationic epichlorohydrin branched β-CD polymer with four different dyes (rhodamine, fluorescein, coumarin and nitrobenzofurazan). Our goal was the development of versatile synthetic strategies, yielding key intermediates of

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• propensity to undergo heterolytic photosolvolysis reactions, most notably o-nitrobenzyl (o-NB) [12], benzyl phenyl ketone (benzoin) [13][14], coumarin-4-ylmethyl [15], and, more recently, p-hydroxyphenacyl (pHP) [15] phosphate esters (Figure 1). While these chromophores exhibit a range of photophysical

• enzymatic studies of ATPase [28][29][30][31][32][33][34]. We [15][28][29][35] and others [6][7][8][9][10][11] have successfully offered alternatives to the o-NB PPG series, initially with benzoin phosphate 2 [13][14] and coumarin-4-ylmethyl phosphate 3. However, the chromophores for these candidates remain

Multichromophoric sugar for fluorescence photoswitching

• Stéphane Maisonneuve,
• Rémi Métivier,
• Pei Yu,
• Keitaro Nakatani and
• Juan Xie

Beilstein J. Org. Chem. 2014, 10, 1471–1481, doi:10.3762/bjoc.10.151

• fluorescence quantum yields were determined by using quinine sulfate dihydrate in sulfuric acid (0.5 N) as a standard at λexc = 325 nm (ΦF = 0.546) and coumarin 540A in ethanol as a standard at λexc = 450 nm (ΦF = 0.544). Photochromic reactions were induced in situ by a continuous irradiation Hg–Xe lamp

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• with activated hydrophilic PEG to enhance its stability (Figure 5) [61]. Bifunctional PEGs were used to introduce a bioactive molecule, for instance biotine, coumarin, cholesterol or mannose into the distal end of a PEG-chitosan complex (Figure 6) [62]. Fructans have been PEGylated by reaction of

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• recorded in dichloromethane and the fluorescence quantum yields Φf were determined with coumarin 1 or p-terphenyl as references (Table 2). The most furans display intense, broad absorption bands between 321 and 358 nm with molar extinction coefficients between 21000 to 35000 L/mol cm−1. In addition

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• . This observation thus firmly validated that the methyl ether had to be situated at C-5, as its alternative location at C-7 would have led to a strong increase in signal intensity of the protons bound to both, C-6 and C-7. Owing to its coumarin core structure and its biological origin, compound 7 was

• of existing coumarin structures in literature, the 5-hydroxy-7-nitro substitution pattern combined with the unusual long-chain, fully saturated alkyl substituent at C-4 are unique to the myxcoumarins 7 and 9. With the production of myxothiazol A (5) and aurachin A (6), the investigated strain

Topochemical control of the photodimerization of aromatic compounds by γ-cyclodextrin thioethers in aqueous solution

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1858–1866, doi:10.3762/bjoc.9.217

• aromatic guests under controlled, homogenous reaction conditions. The quantum yields for unsubstituted anthracene, acenaphthylene, and coumarin complexed in these γ-CD thioethers were found to be up to 10 times higher than in the non-complexed state. The configuration of the photoproduct reflected the

• configuration of the dimeric inclusion complex of the guest. Anti-parallel orientation of acenaphthylene within the CD cavity led to the exclusive formation of the anti photo-dimer in quantitative yield. Parallel orientation of coumarin within the complex of a CD thioether led to the formation of the syn head

• -to-head dimer. The degree of complexation of coumarin could be increased by employing the salting out effect. Keywords: acenaphthylene; anthracene; coumarin; cyclodextrins; photodimerization; quantum yield; stereoselectivity; Introduction Photochemical reactions have been considered highly

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• determine whether we could observe spectroscopically a slug of the coumarin passing through the flow cell. The Raman spectrum of 1 (Figure 2) exhibits strong Raman-active stretching modes at 1608 cm−1 and 1563 cm−1 while the salicylaldehyde and ethyl acetoacetate starting materials exhibit minimal Raman

• s in an automated fashion as the coumarin passed through the cell by using the “continuous-scan” function on our spectrometer. By subtracting the spectrum of the solvent mixture (1:1 ethyl acetate:acetone) from the spectra recorded, we were able to clearly see the growth of the signal due to 1

• signals from the starting salicylaldehyde (9.84 ppm) and the coumarin product (8.45 ppm) [36]. Obtaining a relationship between signal strength and concentration: To obtain a calibration curve, spectra of 3-acetylcoumarin in 1:1 ethyl acetate/acetone were recorded at a range of concentrations by passing

Synthesis and spectroscopic properties of 4-amino-1,8-naphthalimide derivatives involving the carboxylic group: a new molecular probe for ZnO nanoparticles with unusual fluorescence features

• Laura Bekere,
• David Gachet,
• Vladimir Lokshin,
• Wladimir Marine and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2013, 9, 1311–1318, doi:10.3762/bjoc.9.147

• recorded using 1 cm quartz cells. The quantum yield of fluorescence was determined by using coumarin 153 as a reference in toluene and ethanol at 20 °C. Fluorescence lifetime measurements were performed by using time-correlated single photon counting (TCSPC) spectroscopy. Femtosecond pulses (150 fs, 80 MHz

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• and relatively easy to prepare this kind of fluorescent amino acid with the new synthetic method. Furthermore, it can be applied to synthesize other derivatives of the coumarin amino acid with some specific properties. Keywords: coumarin; fluorescent probe; halogen derivatives; non-natural amino acid

• coumarin amino acid 1a (Figure 1) is sensitive to both pH and solvent polarity, which makes it a good probe to investigate protein functionalities and biological processes related to them. The following examples are several applications of it. Shan and co-workers used compound 1a to form a FRET pair with

• were then removed and racemic amino acid 1a was afforded. This approach prevents the tedious and costly HPLC purification step used in approach 1. However, it can only provide compound 1a as a racemic mixture, and some reagents used are not readily available. Due to the great importance of coumarin

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• moderate yields. Keywords: A3 coupling; cooperative catalysis; coumarin synthesis; cycloisomerization; transition-metal catalysts; Introduction An alkyne, an aldehyde and an amine coupling, referred to as A3 coupling [1], has been found as an efficient method for C–N and C–C bond formation that results

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• mixture was subjected to column chromatography without quenching, and all yields were determined as isolated yields. The ee’s were established by chiral HPLC according to racemic standards and literature data [23]. 4-Hydroxy-3-(3-oxo-1-phenylbutyl)coumarin (warfarin). 1H and 13C NMR data were found to be

• )coumarin. 1H and 13C NMR data were found to be in agreement with the literature data [23]. Chiral HPLC: The measurements were performed with an eluent consisting of 80% hexanes and 20% isopropanol on a Diacel Chiralpak AD-H column with 0.8 mL/min flow. The detector wavelength was 254 nm. tR = 12.0 min

• (minor, (S)-enantiomer) and 13.3 min (major, (R)-enantiomer [23]. 4-Hydroxy-3-(3-oxocycloheptyl)coumarin. 1H and 13C NMR data were found to be in agreement with the literature data [23]. Chiral HPLC: The measurements were performed with an eluent consisting of 90% hexanes and 10% isopropanol on a Diacel

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• could potentially be responsible for thioester hydrolysis. We prepared and used synthetic probe 10 [30] (Scheme 3) in order to test this hypothesis. Coumarin-based probe 10 is known to react extremely fast with thiols through a Michael addition reaction. While the fluorescence of 10 is efficiently

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• expense of another property, such as the rate of release [7]. For example, GABA caged directly as an ester with coumarin chromophores is photoreleased quickly, but is quite unstable in (frozen) solution [60]. However, when caged via a carbamate, its release is orders of magnitude slower, but the compounds

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• ) with tert-butyl acrylate (56) to give the Baylis–Hillman product 57, which was subsequently cyclized in the presence of acetic acid to give chromene 58 in a low yield of 24%, together with coumarin 59 in 40% yield (Scheme 20). An asymmetric amine-catalyzed reaction of salicylaldehyde (5) and α,β

• of 2,2-dimethylchromene 45. Synthesis of 2,3-disubstituted chromene 47 by Stukan and co-workers. Ravichandrans synthesis of 3-substituted chromenes 52–55. Synthesis of 3-substituted chromene 58 coumarin 59 by Paye and co-workers. Govender and co-workers asymmetric synthesis of 2-phenylchromenes 62

Cyclization of ortho-hydroxycinnamates to coumarins under mild conditions: A nucleophilic organocatalysis approach

• Florian Boeck,
• Max Blazejak,
• Markus R. Anneser and
• Lukas Hintermann

Beilstein J. Org. Chem. 2012, 8, 1630–1636, doi:10.3762/bjoc.8.186

• elimination to coumarin (2) could be driven by aromatic stabilization (Scheme 2). In fact, a related stoichiometric two-step protocol has been proposed [36]. It appeared to us that the practical problem of developing a mild and convenient catalytic conversion of ortho-hydroxycinnamates to the corresponding

• coumarins could be an ideal test case to show the utility of using organocatalytic rationales for solving a synthetic problem. Results and Discussion The reaction of (E)-ethyl 2’-hydroxycinnamate (1) to coumarin (2) was chosen as the assay to find catalytic activity under mild conditions (Table 1). It was

• initially thought that hydro-heteroatomic nucleophiles such as thiols, which are known to easily undergo hetero-Michael additions [38], could be suitable candidates for the screen. However, coumarin was not formed in the presence of thiols (Table 1, entry 1). We turned our attention to nucleophiles that are

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening. Keywords: benzylation; catalysis; coumarin; chemical diversity; decarboxylative; palladium; substitution; Introduction Coumarins are privileged

• ]. Due to the ambiphilic nature of the heterocyclic ring of coumarin, this core-structure undergoes a diverse array of coupling reactions, such as halogenations [25], cycloadditions [26][27][28][29][30][31][32], conjugate additions [33][34][35][36][37] and transition-metal-catalyzed C–H activation

• ketone enolates to the exo-methyl position of the coumarin core by this method (Table 1). Screening of reaction conditions showed that, in contrast to common decarboxylative benzylation conditions (Table 1,entries 1 and 2) under which nonpolar solvents give the best DcB, the selective mono-alkylation of