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

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• -2-iminoazacycloalkanes is presented, by microwave-assisted ring closure of ω-arylaminonitriles promoted by polyphosphoric acid (PPA) esters. 1-Aryl-2-iminopyrrolidines were easily prepared from the acyclic precursors employing a chloroformic solution of ethyl polyphosphate (PPE). The use of

• synthesis of 1-aryl-2-iminoazacycloalkanes, by ring closure of ω-arylaminonitriles promoted by PPA esters. This reaction constitutes a novel application of such reagents in heterocyclic synthesis. The procedure involves easily available starting materials and requires remarkably short reaction times. It

Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• 1, Table 2). In the cases of Li[Me3AlSPh], NaSMe, and NaOMe, the triazinone 12a was readily obtained after the nucleophilic-addition/ring-closure reaction (entries 2–5, Table 2). For example, similar to benzoxazine [22], treatment of 11a and 11d with lithium trimethyl(phenylsulfido)aluminate Li

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

• C16 of 53. Whether the pyran-ring closure is also mediated by an enzymatic activity or if this reaction is a spontaneous process could not be clarified yet and may be subject for in vitro studies with the purified enzymes. The net-deoxygenation on C8 of pseudomonic acid B (57) is obtained by a

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• heterocyclic phosphonates: (a) the direct electrophilic or nucleophilic phosphorylation of the heterocyclic systems and (b) the ring closure of phosphoryl-functionalized substrates through cyclization or cycloaddition reactions [14][15][16][17][18][19]. Multicomponent reactions (MCRs) constitute one of the

• for the rapid access of heterocyclic phosphonates is the combination of the Kabachnik–Fields reaction with a subsequent ring closure. Thus, the one-pot reaction of 5-chloro-2-pentanone (46) with ammonia and diethyl phosphonate in ethanol lead to the non-isolable intermediate 47 which was directly

• converted to diethyl (2-methyl-2-pyrrolidinyl)phosphonate 48 by ring closure through an intramolecular nucleophilic substitution (Scheme 12). Subsequent oxidation of 48 with m-chloroperbenzoic acid afforded the corresponding N-oxide 49 which was used for the in vitro and in vivo spin trapping of hydroxyl

The role of alkyl substituents in deazaadenine-based diarylethene photoswitches

• Christopher Sarter,
• Michael Heimes and
• Andres Jäschke

Beilstein J. Org. Chem. 2016, 12, 1103–1110, doi:10.3762/bjoc.12.106

• the differences between the one- and two-methyl switches are not due to solvent effects. This latter observation already indicated poor reversibility and fatigue resistance for the one-methyl switches. We therefore undertook absorption measurements over multiple cycles of ring closure by UV and ring

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• 2,1-benzisoxazole-3(1H)-ones is reported. The optimization and scope of this cyclization reaction is discussed. It is shown that an essential step of the ring closure of 2-azidobenzoic acids is the formation and photolysis of 2-azidobenzoate anions. Keywords: aryl azides; azepinones; 2,1

• conditions at room temperature. The proposed photochemical strategy permits the synthesis the high thermo-labile compounds from the class of 2,1-benzisoxazole-3(1H)-ones. Based on the results of the control experiments, it was found that an important stage of the ring closure is the formation of 2

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• , which is responsible for the formation of product 5a. This finding suggests that the hydrolysis occurs on the stage of A2 furnishing A2OH. Afterwards, intramolecular ring closure of A2OH with a relative activation barrier of 23.8 kcal mol−1 leads to 5a in an exergonic process (Scheme 7). At higher

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• muraymycins (Scheme 5) [98]. A fully protected ureidomuraymycidine tripeptide was prepared through lactone opening followed by urea formation and a final Mitsunobu ring closure as key steps. A Strecker reaction of the benzylimine 34 followed by several steps afforded the alcohol 35. A thermal lactonisation as

• obtained precursor 42 was treated with DIAD and PPh3 in a final step for an intramolecular Mitsunobu ring closure to finish the synthesis of the fully protected ureidomuraymycidine 43 (Scheme 5) [98]. In 2010, Ducho et al. reported an alternative synthesis of the naturally occurring uridine-derived

• this producing organism, L-arginine is diastereoselectively hydroxylated to afford (3S)-3-hydroxy-L-arginine. The ring-closure reaction then occurs with formal inversion of the β-stereocenter (but quite likely through an aza-Michael addition to the α,β-unsaturated intermediate) [119][120][121]. The

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• ] of 14 followed by azidolysis [41] furnished 15. 2-Azido-3,4-epoxide 18 was prepared from readily available [42] 2,3-isopropylidene-D-mannosan (16) in five steps (Scheme 2). Tosylation of 16 [43], followed by hydrolysis of the benzylidene acetal [44] and oxirane ring closure [45] at C-4 delivered 1,6

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• thiocarbonyl ylide 3 or 1,5-ring closure to give 1,3,4-thiadiazoline 2. When the rapid elimination of N2 occurs in the presence of the non-converted thioketone 1, the stabilized 1,5-diradical 12 is formed as precursor of the sterically crowded 1,3-dithiolane 10. The alternatively formed 1,3,4-thiadiazolines 2a

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• terminal module, which results in a cis-configured double bond. Through the formation of the cis double bond the sterical arrangement of the nascent chain favors the lactone ring closure which results in the α-pyrone moiety. Hence, the polyketide is released from the assembly line, whereby the thioesterase

• (TE) domain catalyzes the ring-closure and therewith also the off-loading from the PKSI system [79]. A comparable mechanism, in which a TE is involved in off-loading the nascent chain from the PKS assembly line by lactonization, was described for other natural products, e.g., the isochromanone ring

• sterical requirements within the catalytic cavity of CorB and MxnB do not favor the ring closure, thus the second step might take place in solution [90]. It has to be mentioned that the results between CorB and MxnB differ slightly. The in vitro results obtained for MxnB imply that the western chain gets

(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

• Henry ring closure. In 2015, Chen and co-workers envisaged a three-component organo-cascade quadruple reaction, that yielded highly functionalized polycarbocycles [85]. The authors utilized multiple aromatic aldehydes 205 and some 4-substituted cyclohexanones 206, affording the desired products 207 in

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• 10a and 11a can lead respectively to the final benzindenes 5a and 6a. Thus, intermediate 11a undergoes a disrotatory 6π-electrocyclic ring closure [49] via the transition structure TS6 to give the tricyclic species 13a. By an analogous electrocyclic ring closure through TS7, compound 10a is converted

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• . Addition of lithium acetylide 41 to the keto group led to acetal 42. Hydrogenation of the triple bond under basic conditions resulted in cleavage of the acetal and ring closure to the corresponding lactol which was oxidized with chromic acid to furnish γ-lactone 43. An ensuing Dieckmann condensation [32

• allenic sulfone [44] which, upon conjugate addition of diethyl amine followed by hydrolysis afforded a β-ketosulfone. For the following ring closure, the primary alcohol was desilylated and converted to the corresponding allylic carbonate 71. The cyclononene structure 72 was then assembled via a palladium

• -membered carbocycle was realized via a B-alkyl Suzuki–Miyaura cross-coupling reaction. Optimization studies of this key ring closure with different protecting groups on the lactol functionality revealed methyl acetal 135 as the most efficient substrate for this transformation. The challenging key step was

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• function and subsequent ring closure would then lead to the proposed antibiotic 7. The other oxygen atom is lost during biosynthesis und is therefore undetectable. This example shows how well-designed labeling experiments can support biosynthetic investigations especially on highly derivatized and altered

• (42) and B (43) provides an interesting example (Scheme 7) [61]. The proposed mechanism starts with isomerization of farnesyl diphoshate (FPP, 35) to nerolidyl diphosphate (36) followed by 1,10-ring closure to the helminthogermacradienyl cation (37). A 1,3-hydride shift to the allylic cation 38 and

• are in line with the proposed cyclization mechanism starting from geranylfarnesyl diphosphate (GFPP, 53), which undergoes two cyclizations yielding cation 54. A 1,5-hydride shift at C-12 to C-19 leads to the allylic cation 55. Additional ring closure fuses the tricyclic system 56, which rearranges to

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• borohydride in THF, followed by an acidic work-up with aqueous hydrochloric acid to quench the excess of hydride and to precipitate N,N'-dimesitylethylenediammonium dichloride as a stable white solid. A third step afforded the final heterocyclic product upon ring-closure with triethyl orthoformate in the