Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• formation of the stabilized carbocation 11 that may evolve through two pathways. This intermediate may either undergo a ring closure due to the nucleophilic character of the silylated alkyne (pathway A) or react with an oxygenated nucleophile, such as the perrhenate anion, to generate the transient

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• stereocontrolled approach has been developed for the syntheses of tashiromine and epitashiromine alkaloids from cyclooctene β-amino acids. The synthetic concept is based on the azetidinone opening of a bicyclic β-lactam, followed by oxidative ring opening through ring C–C double bond and reductive ring-closure

• reactions of the cis- or trans-cyclooctene β-amino acids. Keywords: alkaloids; amino acids; ring closure; ring opening; stereocontrolled synthesis; Introduction Indolizidine alkaloids are an important class of naturally occurring compounds which have received considerable attention as a result of their

• the indolizidine framework; access to tashiromine in racemic form can be achieved through the alkylation of succinimide, followed by ring closure via acyliminium intermediates [23][24], the reduction of cyclized pyridinium salts [25], iminium cascade cyclization [26], alkyne-mediated hydroformylation

Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines from aziridines

• Hongnan Sun,
• Binbin Huang,
• Run Lin,
• Chao Yang and
• Wujiong Xia

Beilstein J. Org. Chem. 2015, 11, 524–529, doi:10.3762/bjoc.11.59

• haloalkoxy amine intermediate 2a after abstraction of one hydrogen atom from alcohol. Finally, an intramolecular ring closure affords the morpholine product 3a in the presence of KOH [21]. Conclusion In conclusion, we have developed a simple and practicable metal-free protocol for the synthesis of 2

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• bridging and the strain of the desired 17 would be too high for a successful ring closure. Reacting 16 with tetraethylene glycol (TEG) under high dilution conditions (toluene, reflux, 7 d) provides the crownophane 18 in 68% yield (Scheme 2). Likewise, replacement of TEG by pentaethylene glycol (PEG

Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF

• Erdal Ertas,
• İlknur Demirtas and
• Turan Ozturk

Beilstein J. Org. Chem. 2015, 11, 403–415, doi:10.3762/bjoc.11.46

• molecules, obtained from 1,8-diketone ring closure reactions, and coupling reactions, published by our group. Review BVDT-TTF analogues from 1,8-diketones Bis(vinylenedithio)tetrathiafulvalene (BVDT-TTF) 4 (R = Ph, 4-CH3OC6H4, 4-BrC6H4, 4-CH3C6H4, 4-O2NC6H4, 2-thienyl) is a fully unsaturated analogue of

• temperature for 3 h in 90% yield (Scheme 6) [40]. The ring closure reaction of 47 was performed initially using LR, which produced only the thiophene 50, similar to the result obtained by another research group [28]. Next, the reaction was conducted with P4S10, which gave benzylphenyldithiole 49 and the

• reported in 2013 [58]. Their syntheses began with our standard synthesis of a 1,8-diketone 74 having a thiophene in place of a benzenoid aromatic group (Scheme 11). Reaction of the zinc-complex 59 with four mol equivalents of α-bromoketone 72 gave the diketone 74 in 80% yield, subsequent ring closure of

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• reversibility of the ring closure and preferred formation of isomer 7a. Conclusion In conclusion, the first synthesis of the furo[2,3-b]chromene ring system found in hyperaspidinols A (1) and B (2) has been achieved. Analysis of the NMR of synthetic furo[2,3-b]chromenes 7a and 7b and comparison to the data of 1

A facile synthesis of functionalized 7,8-diaza[5]helicenes through an oxidative ring-closure of 1,1’-binaphthalene-2,2’-diamines (BINAMs)

• Youhei Takeda,
• Masato Okazaki,
• Yoshiaki Maruoka and
• Satoshi Minakata

Beilstein J. Org. Chem. 2015, 11, 9–15, doi:10.3762/bjoc.11.2

• ) reductive ring-closure of 2,2’-dinitro-1,1’-binaphthalenes using various reductants such as Na2S and LiAlH4 [20][21], and iii) the Scholl-type cyclization of 2,2’-azonaphthalenes using a eutectic melt of AlCl3/NaCl [22]. However, these methods require harsh reaction conditions such as the use of strong

• diazahelicenes though. Another simple synthetic route to 7,8-diaza[5]helicenes would involve an oxidative ring-closure of 1,1’-binaphthalene-2,2’-diamines (BINAMs) (Scheme 1, iv). However, interestingly enough, this route remains to be explored. Corbett and Holt reported that the oxidation of BINAM with NaBO3

• . Herein we present a facile, straightforward, and moderately functional-group-tolerant synthesis of 7,8-diaza[5]helicenes (benzo[f]naphtho[2,1-c]cinnolines) bearing functional substituents on the helical π-conjugated backbone through an oxidative ring-closure of BINAM derivatives (Scheme 2, the lower

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• unsaturated amide 9 in readiness for a subsequent RCM reaction. Ring closure of 9 proceeded better in the presence of Grubbs’ second generation catalyst [34] to provide the indolizidine derivative 10 in good yield. Similarly, treatment of amine 8 with vinylacetic acid in the presence of EDC/HOBt under

• standard conditions proceeded smoothly to provide the N-tethered diene 11. Ring-closure of compound 11 proved to be more facile, as expected, and the quinolizidine derivative 12 was obtained in higher yield. The four step sequences 6→10 and 6→12 proceeded in overall yields of 56% and 67%, respectively

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• intramolecular nucleophilic attack at its central, highly electrophilic carbon by the adjacent -NH- of the yet unreacted thiourea unit to produce 4 in a first cyclization step (cyclization-I). The second ring closure to generate the 1,2,4-thiadiazole ring may be assisted by one equivalent of methansulfonyl

• energies of the ring closure steps according to our mechanistic hypothesis were computed and found to comply with a facile reaction at room temperature. Experimental General methods. All reagents were utilized as received from commercial suppliers. NMR spectra, infrared spectra, elemental analysis and

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• pyrolysis of the condensation product of benzaldehyde and aniline [6]. The reaction conditions were improved by Morgan and Walls, based on a reaction including a cyclization of phenanthridine by dehydrative ring-closure with phosphorus oxychloride in boiling nitrobenzene [7]. Over the 20th century this

• various substituents, which were nicely summarized by Keller a decade ago [8]. We tried to survey the wide range of synthetic methods applied from 2000 on organizing them by similarity of reactants/catalysts or organic reactions; for instance the anionic ring-closure reactions using Grignard reagents

• diarylmethanes, acridine, xanthene, thioxanthene, etc. It was based on the generation of a benzotriazole-stabilized carbanion followed by oxidation of this carbanion by copper iodide to form a radical. Subsequent elimination of nitrogen followed by ring closure yielded phenanthridine (Scheme 2) [13][14]. In the

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

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

• electrochemical reaction leads to an Umpolung of the functional group with the lower redox potential, triggering the ring-closure reaction between a nucleophilic and an electrophilic site. Another possibility for an intramolecular ring closure is represented by electrochemically induced radical cyclization

• . Intermolecular cyclizations generally fall into two further categories. In the first scenario, an anodically generated nucleophile (cathodically generated electrophile) reacts with an electrophile (nucleophile) present in solution. Consequently, an intermediate is formed, which undergoes ring-closure reaction

• Michael addition/ring closure with in situ generated quinones (section 2.2) and sequential cyclizations involving acyliminium species and alkoxycarbenium ions (section 2.3) represent the majority of recently reported intermolecular electrochemical cyclizations. Cases which do not fall into any of these

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• neuroprotective condensed 2-phenyl-1,4-benzoxazepines rac-7a,b through the diastereoselective domino Knoevenagel–1,5-hydride shift cyclization reaction rac-5→rac-7a,b from the readily available 4-aryl-2-phenyl-1,4-benzoxazepine derivative, rac-5 (Scheme 1). Ring-closure transformations involving C(sp3)–H bond

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• imidazole ring-opening, initiated by the deprotonation at C-1 of the primary cycloadducts 8, followed by ring-closure involving the carbethoxy C=O group, a previously proposed rationale [9]. The formation of pyrrolo[1,2-a]benzimidazoles 5 involves the spontaneous in situ dehydrogenation of the primary

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• formation of the photoproducts 8 and 10 can be explained by intramolecular cycloaddition and formation of resonance stabilized biradicals A/A’ followed by the 1,6-ring closure (Scheme 4). An 1,3-H shift, as in furan and thiophene derivatives [6], and rearomatization to fused oxazole derivatives B/B’ is not

• detected. The 1,6-ring closure of the biradicals A/A’ occurs stereoselectively giving the major products rel-(2S)-8a/rel-(2S)-10 in which the hydrogen on C-2 is oriented toward the methano bridge. The formation of dihydronaphthalene derivative 9, found only on irradiation of 1, is explained by 6π

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

Comparing kinetic profiles between bifunctional and binary type of Zn(salen)-based catalysts for organic carbonate formation

• Carmen Martín and
• Arjan W. Kleij

Beilstein J. Org. Chem. 2014, 10, 1817–1825, doi:10.3762/bjoc.10.191

• Scheme 2 first the epoxide coordinates to the Zn center allowing Lewis acid activation following the ring opening by nucleophilic attack of X. Then, carbon dioxide insertion into the metal–oxygen bond takes place and a consecutive cyclisation step (ring closure) occurs to give the cyclic carbonate and

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• pyrazole precursor. Employing the latter approach we recently presented a novel method for the synthesis of the pyrazolo[4,3-c]pyridine system by Sonogashira-type cross-coupling reaction of easily obtainable 5-chloro-1-phenyl-1H-pyrazole-4-carbaldehydes with various alkynes and subsequent ring-closure

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• from galactose (Scheme 1) [16]. The 1,6-ring closure was produced by the O-debenzylation of the 6-hydroxy group of 4 and the nucleophilic attack of this hydroxy group to C-1, promoted by SnCl4. An optimized synthesis of 2 following this strategy has recently been described with an overall yield of 48

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• . Subsequently, the thus introduced amino group attacks the carbonyl carbon of the mercaptoacetate moiety. This ring closure affords the temporary imide hemiacetal B which is then stabilized upon elimination of the corresponding alcohol to give the desired thiazolidin-4-ones 7–18 (Scheme 3). Furthermore, in

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

• Anastasia S. Kostyuchenko,
• Vyacheslav L.Yurpalov,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2014, 10, 1596–1602, doi:10.3762/bjoc.10.165

• synthesis, efficient ring closure reaction affording a 4H-1,2,4-triazole unit is presented. All target ambipolar compounds display strong photoluminescence with measured quantum yields up to 0.59. Modification of the demonstrated synthetic routes may be exploited for the preparation of longer, specifically

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• )-furanones from activated alkenes and 4-chloroacetoacetates (Scheme 1) [40]. The reaction was found to be general for a wide range of alkenes derived from aromatic and aliphatic aldehydes. The reaction proceeded via Michael addition of the acetoacetate to the alkene with a subsequent palladium-catalyzed ring

• closure of the primary adduct to form the furanone. In this paper, we report our investigations that extend the reaction to heteroatom-containing electrophiles such as imines and diazo esters. Results and Discussion Following the work on nitrostyrenes, Yan et al. also reported a two-step asymmetric route

• uncatalyzed pathway. The second step of the catalyzed route involves the oxidative addition of Pd(0)Ln to the C–Cl bond of Mannich adduct 16 to form 17. The oxy-π-allylpalladium intermediate 18 can then be formed from intermediate 17 [4][5][6][7][8]. The final step of the catalyzed mechanism, i.e., the ring

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• pathway (route I) proceeds without ring opening and after re-protonation it leads to the major cis-isomer 12. The minor route (route II), accompanied by a ring opening of the benzopyranone, proceeds via intermediate IIc, which after ring closure and protonation yielded a mixture of 2a and 13. This

• BF3 complexation as confirmed by the complexation energies (Table 3). Following complexation, the D-ring opening proceeds (Scheme 6), allowing molecular rearrangements and isomerization after ring closure. The observation of the isomerization of 1 (or 2) at C-11 that occurs in EtOAc but not in DMF can

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• phenyl group. The next step of the sequence, a ring closure to indenocircumtrindene (25), was accomplished by FVP. The bromine in the ortho-position of the phenyl group is presumably lost by homolytic bond cleavage, and the resulting aryl radical then cyclizes [6]. Unfortunately, the reaction also

• generates a significant amount of circumtrindene by loss of the phenyl group during the FVP process [58]. In an effort to improve on the yield over the FVP process, solution-phase ring-closure methods were also examined. All attempts to close 29 to indenocircumtrindene (25) by intramolecular arylations

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• and strongly basic conditions [19]. Kang et al. achieved a highly enantioselective synthesis of an isoindolo[2,1-a]quinoline derivative by affecting an intramolecular ring closure on (E)-3-(2-(isoindolin-2-yl)phenyl)acrylaldehyde using camphorsulfonic acid and a chiral pyrrolidine organocatalyst [20