Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• phthalic acid (2) or phthalic acid ester 3 to 1,2-bis(hydroxymethyl)benzene (4) [19], acid promoted ring closure, and subsequent oxidation with hypochlorite in the presence of methanol gives 7 in a moderate yield of 65% [18]. Alternatively, phthalide 5 has been reduced to 1,3-dihydroisobenzofuran-1-ol (6

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• give [1,2-15N2]-tetrazolo[5,1-c][1,2,4]triazine 11-15N2. Indeed, [2,3-15N2]-tetrazolo[1,5-b][1,2,4]triazin-7-one 13-15N2 was obtained (see below). Most likely, tetrazole 11-15N2 underwent a ring-opening process, yielding azide 12-15N2, and this process was followed by an alternative ring closure. This

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• determine that over 90% of the mixture is in the form of 2-azidopyrimidine 4d in CDCl3. This proves the effect of the solvent in the tetrazolo[1,5-a]pyrimidine2-azidopyrimidine equilibrium. The highly polar DMSO-d6 favors the ring closure to form tetrazolo[1,5-a]pyrimidines in larger quantities (3d:4d in a

• nitrogen atom next to the methyl group participates in the ring closure. This equilibrium was not observed in the other compounds addressed in this work. In general, tetrazolo[1,5-a]pyrimidines with 7-CF3 or 7-CCl3 substituents were observed in DMSO-d6 or CDCl3, while 2-azidopyrimidine was found in the

Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole derivatives

• Mio Matsumura,
• Mizuki Yamada,
• Atsuya Muranaka,
• Misae Kanai,
• Naoki Kakusawa,
• Daisuke Hashizume,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2017, 13, 2304–2309, doi:10.3762/bjoc.13.226

• Scheme 1. The key precursor 2 was synthesized by I2-mediated electrophilic cyclization of 2-ethynyl-N,N-dimethylaniline 1 [36][37]. Treatment of compound 2 with n-butyllithium in anhydrous THF at −78 °C and subsequently with PhPCl2 resulted in ring closure, affording the desired benzophospholo[3,2-b

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• first one is the ring closure leading to 9, and the second one involves the addition of a second carbene followed by ring closure to yield 8. The reaction with Z-1b led to the same set of products with trans-orientation of the substituents in 8 indicating the appearance of an intermediate zwitterion 11

• ] (Scheme 26). The formation of the products is initiated by the nucleophilic attack of either C4 or NH2 of 81 onto E-1, followed, in both cases, by elimination of HCN to give intermediates 84 and 85, respectively. The heterocyclization leading to 82 is a lactamization, whereas a ring closure via N attack

• succinate 91 (see chapter Michael type reactions) [54] (Scheme 28). In this case, the reaction pathway comprises the ring closure through the attack of the O-nucleophile onto the terminal cyano group. The analogous reaction was reported for the enolizable indane-1,3-dione. Redox reactions The replacement of

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• -ring formation was investigated in non-activated systems, 5,7,8,13-tetrahydro-6,13-methanodibenzo[c,f]azonine was exclusively obtained. Furthermore, selective ring closure in the para-position could be achieved under standard PFB conditions, while a double ring closure could be obtained utilizing HClO4

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• principal approaches have been used to establish the 12-membered macrolactone ring, namely (1) ring-closure by macrolactonization, the approach followed by Kishi, Negishi and Aggarwal, or (2) ring-closing olefin metathesis (RCM) to form the C8–C9 double bond, which is part of Burkart’s and Altmann’s

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• isocyanide Pd complex followed by the ring closure [32]; on the other hand, the arylation of benzothiophene in the presence of Pd(OAc)2/PCy3*HBF4/PivOH proceeds in accordance with the concerted metalation–deprotonation mechanism [33][34]. We also investigated the reaction of zinc meso-(3-bromophenyl

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• -assisted ring closure of the corresponding aminoamides promoted by ethyl polyphosphate (PPE). Keywords: dihydroquinazolines; microwaves; N-acylations; N-alkylations; PPE; Introduction Nitrogen heterocycles are part of many drugs and represent structures with wide therapeutic potential. Therefore, much

• microwave irradiation at 110 ºC for 4 minutes. Due to the easier preparation and the inexpensive reagents required for its synthesis [65], PPE was chosen as cyclodehydrating agent for the preparation of compounds 1. Results and optimized experimental conditions of the MW-assisted ring-closure reaction are

• nucleus almost unexplored. To our knowledge, this is the first general method available for synthesis of these compounds. The products were synthesized by microwave-assisted ring closure of different aminoamides promoted by PPE. The yields and reaction times involved in the heterocyclization step compare

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• natural fusaricidin by the Jolliffe group employed a ring closure via a lactonization in solution and subsequent attachment of the side chain to the cyclized depsipeptide [10]. Since the macrolactonization approach suffered from diastereoselectivity issues and low yield, it was decided to perform an on

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• C10 and C12. Based on this analysis, their synthetic plan was to first build the triene, while the C2–C5 fragment should be constructed directly before or during ring closure as shown in Scheme 2. Consequently, they first planned to connect the north-eastern fragment 5 with the propionate unit 4 by a

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• hydrolysis of the Cbz group to some extent. The final ring-closure to the CD-ring fragment 20 was successfully achieved with 31% yield over 3 steps. Only the desired (E)-6-exo 18 isomer reacted, leaving the (Z)-exo isomer 19 uncyclized, as anticipated. Inspired by the successful Cbz deprotection of a very

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• intramolecular ring closure [21][22][23][24]. The importance of these cores for medical chemistry studies suggests that isotopically labeled pyrazolo[1,5-a]pyridines and triazolo[1,5-a]pyridines could be of interest. Recently, deuterium-labeled pyridinium-N-imines were applied to mechanistic studies of the

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• phosphazene bases in deprotonating carboxylate dithianes, we selected the commercially available achiral superbase P2-t-Bu phosphazene to initiate the ring closure (Scheme 2) [31][32]. We found that in the simplest case, with the methyl-substituted para-quinol ester (1a), the reaction was complete in 30 min

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• reaction is based on the formation of β-oxo-N-propargyl thioamides A as intermediates, followed by their spontaneous ring closure. This reaction was run in refluxing ethanol and provided in all cases the desired thiazolidines 42 in high to excellent yields (Scheme 10) [93]. In 2009, Yarovenko and co

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• yields of up to 74% and trace amounts of the auto-condensation products 6 (Scheme 3). Even in the deactivated derivatives containing halogen atoms at the aromatic system, the cyclopentanone ring closure took place quite easily [14]. If other Lewis acids, such as Bi(NTf2)3 or triflate derivatives of the

• 76% yield. The former 271 was obtained from the trienone 270/270’ which underwent ring closure to give the 6-membered ring [105] (Scheme 76). 2.2 From alkynes DBU and CpRu(PPh3)2Cl dual catalysts enabled a one-pot annulation of aldehyde 273 and cyclopentanone (274) to give the 1-indanone derivative

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• computational methods. The preferred formation of the unusual macroheterocycle, competitive with the 1,3-ring closure leading to a thiirane and the head-to-head dimerization yielding a 1,4-dithiane derivative, respectively, was explained based on the analysis of the structure of the favored conformer of the

• ], suggests that it is formed via the intermediate delocalized 1,7-diradical 8D, which dimerizes to give the 1,14-diradical 12D and subsequently undergoes the ring closure yielding product 9 identified as the rac-diastereoisomer. The goal of the present study was the examination of the postulated reaction

• pathway via a diradical intermediate leading to the formation of the unusual macrocyclic dimer 9 by computational methods. First calculations were made for phenyl selenophen-2-yl thiocarbonyl S-methanide (8A), which can undergo a 1,3-dipolar electrocyclization (1,3-ring closure) to form the thiirane 3a

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• five- (4) and seven-membered ring (6), three-membered aziridine rings were not detected. Competing N- and O-alkylation was observed at higher temperatures with ethanolamine (8) and 6-amino-1-hexanol (5), suggesting ring closure is slower in these cases. Ethanolamine (8) produced dimers as the major

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• ) as a solvent resulted in competitive amide formation from the decomposition product of DMF at high temperature. In order to prevent this we switched to N,N-dimethylacetamide (DMA) as the solvent. We next focused our efforts on combining this optimized oxadiazole ring-closure procedure with our

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

• 3 can then react with the nucleophilic α-carbon atom of β-ketoester 4 to an open chain ureide 5. Subsequent ring closure results in a hexahydropyrimidine intermediate 6. In the last step, the irreversible elimination of water forms the thermodynamically favored DHMP product 7. This accepted

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• alcohol derivative 27 in 51% yield as 96:4 mixture of two diastereomers (Scheme 9). Subsequent ring closure of γ-amino alcohol 27 by treatment with mesyl chloride in the presence of triethylamine [53] furnished the N-mesylated pyrrolidine derivative 28 in 65% yield with excellent diastereoselectivity (dr

• alcohols 27a,b and subsequent ring closure to pyrrolidine derivatives 28a,b. Hydrogenation of 1,2-oxazine anti-24 to products anti-29 and anti-30. Supporting Information Supporting Information File 399: General information, all experimental procedures and analytical data. Supporting Information File 400

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• one-pot reaction for the synthesis of 2-heptyl-chromen-4-one (1-O-HHQ, 4) which includes esterification, Baker–Venkataraman rearrangement and subsequent acid-catalyzed ring closure to affort the 1-O-HHQ in 60% yield [36] (Scheme 1). The 2-heptyl-3-hydroxychromen-4-one (1-O-PQS, 13) was previously

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• acid precursor is often oxidized near the end of the chain to form a polar hydroxy acid. The following ring-closure reduces the hydrophilicity of the compound and increases its vapor pressure, making the resulting macrocycle well-suited to serve as a signal [1]. Fatty acid derived macrolactones were

• ω − 1 oxidation and ring closure [15]. Another possibility would be that a common saturated acid such as stearic acid is chain-shortened first to tetradecanoic acid, on which a common Δ9-desaturase is acting, leading after ω − 1 oxidation and ring closure to tetradec-9-en-13-olide (2). Therefore, we

• -dodecenolides, 12-tridecenolides and isomerized 13-tetradecenolides were obtained. In addition, ring expanded 14-pentadecenolides were observed. The latter can be explained by dimerization of esters 9 or 17, isomerization of the double bond, and final ring closure, leading to either ring-contracted or expanded

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• resulted in ratio of 2:1 by peak integration (i.e., HB = 2H), indicating the cyclisation via (S)-LPP ((S)-5) and the (S)-terpinyl cation ((S)-6) (Scheme 1, right). Syn versus anti addition in the final ring closure The final cyclisation step from (S)-7 via 8 to 1 can in principle proceed either via a syn

Isosorbide and dimethyl carbonate: a green match

• Fabio Aricò and
• Pietro Tundo

Beilstein J. Org. Chem. 2016, 12, 2256–2266, doi:10.3762/bjoc.12.218

• -membered ring is a preferred pathway compared to other possible ones (7-membered ring closure, alcoholate attacks onto DMC) due to a big entropic effect [35]. Reactivity of isosorbide with dimethyl carbonate One of the most investigated research fields for the sustainable platform chemical isosorbide is