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

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• -membered ((S,R)-INT3 and (S,S)-INT3) or six-membered ((S,R)-INT3’ and (S,S)-INT3’) intermediate bicyclic imidazolinium cations. Energy profiles for both 5-exo and 6-endo pathways are presented in Figure 3. The ring closure reactions are carried out via four transition states: two for the formation of the

• and susceptible to the nucleophilic attack of N(1) atom. Subsequent ring closure is the rate-determing step and also the step in which the cyclization mode and distribution of the products is determined (Figure 3). This process was followed in 1H NMR experiments by the increase of the signal

• intermediate imidazolinium cations. The last step of the reaction is deprotonation followed by the formation of the fused bicyclic hydantoins. DFT calculations support a plausible reaction pathway where the ring closure is the rate-determining step. The preferred 5-exo cyclization is confirmed. Elucidation of

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• : a sequential aldol condensation of dihydrocarvone with norbornene 2-carboxaldehyde followed by a ROM–RCM of the resulting aldol product. The norbornene derivative 164 was subjected to a RRM using the catalyst 1 to produce the ROM product 165 exclusively. The ring-closure of the resulting ROM product

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

• ][28]. Thus, the indole NH group (pKa about 21 in DMSO) should be able to serve as a stoichiometric proton source that, after β,β'-coupling, would convert one of the Sm(III) enolates to the ketone. Attack of the remaining Sm(III) enolate would lead to Dieckmann-type ring closure, followed by

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• converted into an amide in the presence of methylaminoacetaldehyde dimethylacetal. A ring closure occurs by treating the amide with a strong acid. The reaction gave a mixture of a quinone and a dimethoxy intermediate that were first reduced to amine products. Furthermore, the dimethoxy intermediate was

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• -step synthesis avoiding chromatographic work-up. In the key step triethyl orthoformate is reacted with the corresponding N1,N2-diarylbenzene-1,2-diamines and then further transformed in situ, by alkoxy abstraction using trimethylsilyl chloride (TMSCl), and concomitant imidazole ring closure. Keywords

• of nucleophilic aromatic substitutions (SNAr) of benzene-1,2-diamine at 2-chloropyridine (Scheme 1). Once all the different N1,N2-diarylbenzene-1,2-diamines were prepared a method had to be developed to build up the imidazolium salts by ring closure. 3-Cl and 4-Cl could principally be obtained from

• stability of the [BF4]− anion could lead to complications generating side-products [50][51][52]. The preparations of both 3-Cl and 4-Cl started along the given lines with the syntheses of the respective aryl-substituted diamines, which had to undergo ring closure in the presence of a C1 component. For 3-Cl

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• in an aqueous dispersion of a Pt-TiO2 catalyst, an interesting self-reaction occurred. Ohtani and co-workers isolated modest yields of secondary amines 13 that were formed via C–N coupling (Scheme 4, top) [48]. Terminal diamines reacted by ring closure resulting in cyclic amines 14; pyrrolidine was

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• -acetamido-3-deoxy-α-D-psicofuranose 11 resulted in ring closure of the acetamido group, affording 2-methyloxazoline derivatives 13 and 14. Further research into an alternative strategy for the synthesis of 3-azido-3-deoxy-D-psicofuranose derivatives will be performed so as to avoid the formation of the 2

Cross-metathesis reaction of α- and β-vinyl C-glycosides with alkenes

• Ivan Šnajdr,
• Kamil Parkan,
• Filip Hessler and
• Martin Kotora

Beilstein J. Org. Chem. 2015, 11, 1392–1397, doi:10.3762/bjoc.11.150

• vinyl β-C-deoxyribofuranoside was based on transformation of 6-O-tert-butyldiphenylsilyl-3,5-dideoxy-5-iodo-L-lyxo-hexofuranose [14]. A reaction sequence relying on Horner–Wadsworth–Emmons/ring closure–halogenation/Ramberg–Bäcklund/Wittig reaction gave rise to the equimolar mixture of styryl α- and β-C

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• CO2, catalysed by LiBr [41]. The preferred pathways principally involve ring opening of the epoxide, followed by CO2 insertion and ring closure of the cyclic carbonate. Interestingly, in the Re(I)-catalysed reaction (b), an alternative reaction pathway was followed, whereby the first step is CO2