Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• recycle experiment paved the way for the application of 5 in continuous-flow processes with long-term stability. Next, the heterogeneous procedure for the activation of aromatic α-diketones was applied to the model Stetter-like reaction of benzil 1a with chalcone 9a serving as activated α,β-unsaturated

• previous study on the benzoin condensation, the Stetter-like reaction of benzil (1a, 0.1 M) with chalcone 9a (0.05 M) was optimized at 70 °C with a flow rate of 5 μL min−1 (Table 5, entry 1). Because of the partial adsorption of the target 1,4-diketone 10aa onto the basic packing material 5, the reactor R5

• solution of α-diketone 1 (0.10 M) and chalcone 9 (0.05 M), and operated at 70 °C with a flow rate of 5 μL min−1 for 5 h under steady-state conditions. After that time, the reactor was flushed at room temperature with pure DMF for an additional 5 h. The collected solution was finally concentrated and eluted

Synthesis and characterization of fluorinated azadipyrromethene complexes as acceptors for organic photovoltaics

• Forrest S. Etheridge,
• Roshan J. Fernando,
• Sandra Pejić,
• Matthias Zeller and
• Geneviève Sauvé

Beilstein J. Org. Chem. 2016, 12, 1925–1938, doi:10.3762/bjoc.12.182

• good performance. More work is underway to better understand the mechanism for the enhancement, and will be published separately. Experimental Materials Chalcone (Acros), 4-fluorochalcone (TCI America), 4’-fluorochalcone (TCI America), 4,4’-difluorochalcone (TCI America), 1-ethynyl-4-fluorobenzene

Synthesis and properties of fluorescent 4′-azulenyl-functionalized 2,2′:6′,2″-terpyridines

• Adrian E. Ion,
• Liliana Cristian,
• Mariana Voicescu,
• Masroor Bangesh,
• Augustin M. Madalan,
• Daniela Bala,
• Constantin Mihailciuc and
• Simona Nica

Beilstein J. Org. Chem. 2016, 12, 1812–1825, doi:10.3762/bjoc.12.171

• hours, the desired 4′-azulenyl substituted terpyridines are obtained as trace compounds, the yields of the reaction do not exceed 10%. Alternatively, the desired 4′-azulenylterpyridines can be isolated using a step-by-step reaction protocol, without the isolation and purification of the chalcone

• , diethyl ether (30 mL) was added and the formed precipitate filtered off. After column chromatography on silica gel as mentioned above, the desired chalcone was isolated (180 mg, 69.5%). Route C. Azulen-1-carboxaldehyde (156.0 mg, 1.0 mmol), 2-acetylpyridine (121.0 mg, 0.11 mL, 1.0 mmol) and NaOH (40.0 mg

• , 1.0 mmol) were suspended in water (1.5 mL) in a microwave vial of 2 mL. The reaction mixture was introduced in a Biotage apparatus and irradiated for 15 min at 110 °C. After column chromatography on silica gel with 2% ethanol in dichloromethane chalcone 2a was isolated (174 mg, 67%). (E)-1-(Pyridin-2

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• consumption of hydrogen peroxide. It has been shown that the AS is substrate tolerant and accepts different hydroxylation patterns as well as glycosylations on the chalcone A and B rings [154]. However, the oxidative half-reaction only occurs with chalcones and not with other aryl substrates like L-tyrosine

• dehydrative aromatisation. ACSs show high similarity on the amino acid level to other type III PKS systems like chalcone synthases and benzalacetone synthases, but their strict substrate specificity for nitrogen-containing starter units avoids mispriming with precursors of the latter group of enzymes [172

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• . Copper(II) was attached by coordination to a terpyridyl ligand. The spacer length was varied in the back of the ligand framework. These biohybrid catalysts were shown to be active in the Diels–Alder reaction of a chalcone derivative with cyclopentadiene to preferentially give the endo product. Keywords

(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

• tetrasubstituted, in good yields and selectivities. In 2013, Luo, Xu and co-workers demonstrated an easy method for the synthesis of enantiomerically pure polysubstituted chromans 99, via the reaction of chalcone enolates 100 and nitromethane (101), catalyzed by quinine-derived thiourea 56 (Scheme 33) [52

• ]. Initially nitromethane adds to the chalcone moiety, followed by a nitronate addition to the α,β-unsaturated ester. The substrate scope was widely expanded, including the aromatic moieties containing halogens, alkyl and alkoxy groups. Also, ketones bearing aryl, heteroaryl and alkyl groups, provided the

• and co-workers disclosed an elegant synthesis of polysubstituted cyclohexanes, utilizing the chiral adduct 107 of the Michael reaction of chalcone 109 catalyzed by a bifunctional thiourea 56 [54]. The authors used a range of different adducts, as well as monosubstituted and disubstituted α,β

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• proceeded uneventfully to afford the corresponding 2-methyl-3-arylsulfonyl-4H-chromene derivatives 8aa–8ib (Scheme 4). The annulation reaction appears to be general as evident from the results in Scheme 4. The chalcone component can accommodate chloro, bromo and methoxy groups as aromatic substituents

• extend the annulation reaction to phenols with other Michael acceptors at the ortho-position (such as unsaturated esters, enals and nitroolefins) were not successful. Additionally, a very low yield (ca. 10%) of the product 8aa was obtained when the chalcone formation (7a) and its annulation reaction with

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• modularity of the Chan–Lam coupling process, and proceeds through a pathway that is distinct from the Liebeskind copper-catalyzed C–N bond coupling and electrocyclization (Scheme 2). Results and Discussion A Chan–Lam coupling between chalcone oxime 6a and cyclohexenylboronic acid (7a) was initially tested

• , the scope of the nitrone synthesis was explored by varying the oxime and alkenylboronic acid reagents. As shown in Table 2, chalcone oximes with both electron-rich and electron-poor aryl substituents, as well as heteroaryl substituents, were tolerated for the transformation with electron-donating

• substituents providing higher yields (Table 2, entries 1–4). A significant increase in reaction efficiency was also observed for dba oxime (Table 2, entry 5). Evaluation of acyclic alkenylboronic acids further highlighted the differences between dba oxime and chalcone oximes as substrates for the Chan–Lam

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

• pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and

• IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro. Keywords: antimicrobial; chalcone; cholesterol; cytotoxicity; glycoside; triazole; Introduction Cholest-5-en-3β-ol (cholesterol, 1

• cell line but it was 2.3 fold less active than doxorubicin in vitro. Therefore, this article describes the synthesis of analogues of VI with different lipid, glycon and chalcone [25][26] tags to assay and evaluate their in vitro antimicrobial and cytotoxic activities against the above mentioned

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• , exclusive trans-arrangement of aryl substituents at the cyclopentane ring had been observed [21][22][23][24]. Aryl substituents generally prefer the antiperiplanar arrangement, as observed by Zhou and Zhang, who reductively dimerized chalcone derivatives to trans-diarylated cyclopentanols [23]. Cis isomers

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• superior inhibition to that of the natural parent product. This work was followed by more comprehensive bioactive studies on aromatic enones utilizing the substituted chalcone backbone [26]. The study showed that the presence of the enone moiety played an important role in maintaining the activity in the

• of alkyl groups instead of acyl groups enhanced the antimicrobial activity and stability at pH 7.4. Xanthohumol Xanthohumol (XN, 58), a naturally occurring prenylated chalcone in hop plants (Humulus lupulus L., Cannabaceae), has been suggested to have potential to suppress the development and

2-(1-Hydroxypropyn-2-yl)-1-vinylpyrroles: the first successful Favorsky ethynylation of pyrrolecarbaldehydes

• A. V. Ivanov,
• V. S. Shcherbakova,
• I. A. Ushakov,
• L. N. Sobenina,
• O. V. Petrova,
• A. I. Mikhaleva and
• B. A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 228–232, doi:10.3762/bjoc.11.25

• the more basic KOH was shown to promote a subsequent chalcone formation after ethynylation of 4,5-dihydrobenzo[g]indole-2-carbaldehyde (which contains a pyrrole-2-carbaldehyde moiety) with phenylacetylene [21]. As shown on the example of benzaldehyde [22], other ratios of the catalytic composition

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• case due to the Thorpe–Ingold effect [46]. Recently, Zeng, Little and co-workers reported a new electrochemical method for the preparation of 3,5-disubstituted isoxazoles from chalcone oximes 20 (Scheme 8) [47]. The electrolysis of 20 is carried out in an undivided cell under galvanostatic conditions

• ester 12. Preparation of pyrrolidines and tetrahydrofurans via Kolbe-type electrolysis of unsaturated carboxylic acids 16. Anodic cyclization of chalcone oximes 19. Generation of N-acyliminium (23) and alkoxycarbenium species (24) from amides and ethers with and without the use of electroauxiliaries

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• a significantly greater influence on the stabilization than the corresponding chalcone system. Thus, there is a good correspondence between the theoretical and experimental results, both of which support that Rh(II)-catalyzed reactions of diazo compounds with isoxazoles do not involve the formation

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• or ketones [23]. The most practical approach to a 2,4-disubstituted pyrrole reported to date is the recently disclosed microwave-assisted Stetter reaction of chalcone with carbohydrates as “green” formaldehyde equivalents followed by a microwave-assisted Paal–Knorr cyclization of the resulting 1,4

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• , chalcone derivatives are the most widely used dipolarophiles. Sarrafi and co-workers reported a 1,3-dipolar cycloaddition reaction of isatin, benzylamine and chalcone derivatives [31], and only one single regioisomer was obtained in high yield, in which the benzoyl group was connected to C-3 of the newly

• ethanol at room temperature (Table 1). It smoothly went until completion. Interestingly, the two regioisomers 4a and 5a were obtained with modest yield and poor regioisomeric ratio (Table 1, entry 1), which is quite different from the reaction of chalcone. Generally, only a single regioisomer 4′,5

• ′-diarylspiro(indoline-3,2′-pyrrolidin)-2-one was formed when using chalcone or dienone as dipolarophiles [20][31]. Presumably, this might be attributed to the electronic and steric effects of the acetyl group. Therefore, reaction conditions including various solvents and additives (Table 1, entries 2–9) were

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• sulfone, trans-1,2-bis(phenylsulfonyl)ethylene, chalcone, crotonaldehyde and cinnamaldehyde at the same reaction conditions [36]. Another drawback was the poor reactivity observed when α-substituted azlactones were used as starting material in the named reaction with NPM. However, the alanine-derived 4

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• such as chalcone is very tough, presumably due to the hardness of the CF3 anion. Recently, we reported the copper-mediated trifluoromethylation at the benzylic position by using shelf-stable electrophilic trifluoromethylating reagents, S-(trifluoromethyl)diphenylsulfonium salts, in good to high yields

• chalcones. During the preparation of this article, the Nicewicz group showed a single example of conjugate trifluoromethylation of chalcone with sodium trifluoromethanesulfinate salt in the presence of N-methyl-9-mesitylacridinium as a photoredox catalyst resulting in a low product yield of 31% as a mixture

• our investigation with the reaction of chalcone (1a) using a series of electrophilic trifluoromethylating reagents 3 [23][24][25][26] in the presence of copper in DMF at 60 °C (Table 1), based on previously reported conditions [21]. First, the trifluoromethylation of 1a with S-(trifluoromethyl

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

• effect on the outcome of the reaction (Table 2, entries 3 and 4). The Claisen–Schmidt condensation We moved next to study the Claisen–Schmidt condensation of benzaldehyde with acetophenone to yield chalcone (Scheme 3). Chalcones display interesting biological properties such as antioxidant, cytotoxic

• the Raman spectrum. We also observed a significant “tail” on the plot of signal intensity at 1604 cm−1 vs time. We attribute this to the fact that the chalcone product is very highly Raman active and even a trace in the flow cell can be readily detected. It does however highlight the fact that there

• = 10 s). Monitoring the conversion of benzaldehyde with acetophenone to chalcone, 3a, across a range of reaction conditions (scan time = 15 s, integration = 10 s). Monitoring the conversion of benzaldehyde, ethyl acetoacetate, and urea to 5-ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H

Total synthesis of ochnaflavone

• Monica M. Ndoile and
• Fanie R. van Heerden

Beilstein J. Org. Chem. 2013, 9, 1346–1351, doi:10.3762/bjoc.9.152

• moieties, and the permethyl ether of 2,3,2'',3''-tetrahydroochnaflavone have been achieved. The key steps in the synthesis of ochnaflavone were the formation of a diaryl ether and ring cyclization of an ether-linked dimeric chalcone to assemble the two flavone nuclei. Optimal experimental conditions for

• nucleophilic substitution and chalcone formation as the key steps. Results and Discussion Our synthesis of 1 is summarized in Scheme 1. The two most important steps in the synthesis of 1 are the formation of the diaryl ether linkage and the assembly of the flavone nuclei. The most logical approach to the

• formation of the chalcone by an aldol condensation reaction with a suitably substituted acetophenone. Selective methylation of 2,4,6-trihydroxyacetophenone with methyl iodide yielded 2'-hydroxy-4',6'-dimethoxyacetophenone (5) in moderate yield. The Claisen–Schmidt condensation of 5 with diaryl ether 4 under

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• resulted in a variety of radiolabeled molecular probes for in vivo PET/SPECT imaging. The scaffolds from which these newer radiolabeled probes are derived include chalcone (5) and its conformationally restricted analogues flavone (6) and aurone (7); stilbene (8) and its analogues diphenyl-1,2,4-oxadiazole

• introduce radiolabels into PET probes are outlined in Scheme 1. These general strategies will be abbreviated as Gs A–D in all subsequent schemes in this review. Chalcone and its conformationally restricted analogues Chalcone derivatives Chalcones and indolochalcones, such as 18a–l, 19a,b, 20a,b, and 21

• pegylation (n = 0–3) all showed similar affinity. In biodistribution experiments using normal mice, the [18F]-labeled chalcone 19a showed high brain uptake rate and good clearance, whereas the [11C]-labeled chalcone 19b revealed reasonable brain uptake rate, but very fast clearance [14]. The [18F]-labeled

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

• a C-2 phenyl substituent. The synthesis of flavans and flavones generally involves treatment of acetophenone (7) with a base to give enolate 8, which undergoes a Knoevenagel condensation with salicylaldehyde (5) to yield a chalcone 9. These chalcone derivatives are then cyclized by using various

• temperature to give chalcone 14. To set the stage for the cyclisation reaction, the trans carbon–carbon double bond must either be isomerized to the cis form or completely reduced. In this case, chalcone 14 was treated with H2 in the presence of a catalytic amount of Pd to give intermediate 15 in 99% yield

• acetophenone derivatives 7 to give the corresponding chalcones of type 9 in 66–85% yields. Contrary to Xue’s reduction method where H2/Pd was used, we used NaBH4 in the reduction of both the carbon–carbon and carbon–oxygen double bonds of chalcone derivatives 9 to give the corresponding alcohols 17. It is

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• synthesis starts with 6-carboxy-2-acetylpyridine (20), which is reacted with furfural (1), thus providing chalcone 21. This is then reacted with di-pyridinium salt 22 in the presence of ammonium acetate to afford quinquepyridine 23 (Scheme 4). Another possibility to access the key intermediate “1,5-diketone

• . Nevertheless, it was demonstrated that also asymmetric tpys are accessible via the 1,5-diketone pathway [31]. Michael addition of ethyl picolinoylacetate 29 to chalcone 30 affords diketone 31 in 60% yield. Reaction with ammonium acetate to effect ring closure did not yield a terpyridine, but instead

Continuous-flow hydration–condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst

• Magnus Rueping,
• Teerawut Bootwicha,
• Hannah Baars and
• Erli Sugiono

Beilstein J. Org. Chem. 2011, 7, 1680–1687, doi:10.3762/bjoc.7.198

• was purified by column chromatography (n-hexane/DCM [2:1 to 1:1]). The schematic arrangement of the continuous-flow system. Preparation of chalcone 3b on larger scale. Optimization of hydration–condensation reactions.a Flow hydration–condensation of alkynes 1 and aldehydes 2.a Supporting Information

Continuous flow hydrogenation using polysilane-supported palladium/alumina hybrid catalysts

• Hidekazu Oyamada,
• Takeshi Naito and
• Shū Kobayashi

Beilstein J. Org. Chem. 2011, 7, 735–739, doi:10.3762/bjoc.7.83

• double and triple bonds in various substrates are shown in Table 1; these proceeded quantitatively at room temperature under neat conditions. The products were obtained at approximately 10 g/h through the 4 cm3 column. The hydrogenation reactions of trans-stilbene and trans-chalcone, as representative

• solid substrates (Scheme 2), were also examined. The substrates were dissolved in toluene or ethyl acetate. The reduction of trans-stilbene proceeded quantitatively, but an overreaction product was obtained (7% yield) in the reduction of trans-chalcone. We then investigated the hydrogenation of a nitro

• , CDCl3) δ 7.46–7.50 (m, 2H), 7.60–7.63 (m, 1H), 8.12–8.14 (m, 2H). Schematic diagram of the continuous flow reactor (left) and the column top (right). Hydrogenation of ethyl cinnamate. Hydrogenation of trans-stilbene and trans-chalcone. Hydrogenation of nitrobenzene and deprotection of the Cbz group