The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• carbenes and nitrenes generated from sulfonate esters prefer 6-membered ring formation (i.e., 1,6-insertion) opened the door for easy access to 1,3-functionalized products via C–H insertion [64][65]. The sulfonate can be a useful functional group for subsequent transformations, also. If used in the

• profound effect on the preferred C–H insertion location (Scheme 14). As has been noted for other intramolecular insertions [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65], five-membered ring formation is generally preferred over other ring sizes. Thus, the

• sterically hindered catalyst such as Rh2(esp)2 or Rh2(OPiv)4 is needed to prevent dimerization of the diazoacetate. These catalysts are presumed to protect the carbene intermediates from intermolecular reactions long enough to adopt the correct conformation for bridged-ring formation. An exploration of the

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• reductive steps are optional in PKS biosynthesis, and considering the pyrone ring formation, an unsaturated PKS chain residue attached to the carrier is essential. This general PKS catalyzed mechanism is accomplished by different enzymatic machineries. In the following section the three PKS types which can

• investigated in detail. In vitro assays using NAC thioesters of the western and eastern chains in the biosynthesis of 36 [88], as well as simplified substrate mimics of both antibiotics [88][89] provided experimental evidence that the free-standing ketosynthases are responsible for the α-pyrone ring formation

• substrates, i.e., this resulted in a 12-fold increase of product formation. This is an additional hint that protein–protein interactions represent an important factor in PKS systems. Further, it seemed that the carrier proteins conferred specificity for α-pyrone ring formation, since once the carrier

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

• : benzimidazolium salts; bulky ligands; cyclization; ligand design; N-heterocyclic carbenes (NHC); ring formation; Introduction Imidazole-based N-heterocyclic carbenes (NHCs) are stable systems serving as ancillary ligands mainly to construct organometallic complexes. These NHCs are sterically and electronically

• and 4-Cl the synthetic procedures proceed without noticeable problems, while complications were faced in the synthesis for 1-Cl and 2-Cl, particularly during the benzimidazole ring closures. Excluding the procedure of Borguet [42][43] all the known procedures to accomplish imidazole ring formation [44

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• ethynylene)s comprising a cinnoline core were prepared in high yields via a three-step methodology. A Richter-type cyclization of 2-ethynyl- and 2-(buta-1,3-diynyl)aryltriazenes was used for cinnoline ring formation, followed by a Sonogashira coupling for the introduction of trimethylsilylethynyl moieties

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• barriers of quaternary carbon and six-membered ring formation. The use of the second nucleophile and a fast initial trapping reaction reduced the cation character of the radical cation intermediate, slowed competitive elimination reactions, and allowed for the desired quaternary carbon formation. In these

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

• . The TS 9‡ corresponds to the initial nucleophilic attack onto the nascent carbodiimide and is located at 14.9 kcal mol−1 whereas the introduction of solvent reduces the barrier to 9.9 kcal mol−1 (Scheme 3). There are two possible pathways for the MeSO2Cl assisted 1,2,4-thiadiazole ring formation

• , namely cyclization-IIa and cyclization-IIb (Scheme 2). It was very difficult to locate 14‡ in cyclization-IIa, the transition state for the second heterocyclic ring formation, due to a complex reaction coordinate (Figure 3). We were only successful considering that it may be promoted by a proton binding

• locate the DMAP-assisted TS for 1,2,4-thiadiazole ring formation via cyclization-IIb due to a complex reaction coordinate. Conclusion We report on a straightforward methodology to prepare three substituted benzimidazole-fused 1,2,4-thiadiazoles via a methanesulfonyl chloride assisted cyclization between

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 construction of heterocycles have been reported in recent years. These cases demonstrate that ring formation can be achieved efficiently under ambient conditions without the use of additional reagents. In order to account for the recent developments in this field, a selection of representative

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• groups since previous RCM studies [33] showed that the productive RCM for 8-membered ring formation was observed only for the S,S- configured trienes in the presence of an exo-methyl group at the allylic position (Figure 1). Initial attempts were focused on generating the first set of five polyols

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

• the pyrazolo[4,3-c]pyridine system can be mainly achieved through two different approaches. One strategy involves the annelation of a pyrazole ring onto an existing, suitable pyridine derivative [16]. Alternatively, the bicyclic system can be accessed by pyridine-ring formation with an accordant

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

• complex products and bioactive compounds. Among the glycosans, the anhydro sugars involving the anomeric center in the ring formation, the 1,6-anhydro sugars are the most common and useful building blocks [1][2]. They can play a role in synthetic methodologies aiming at the obtainment of regioselectively

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• in S. cinnamonensis [15][16][17][18][19][20], but much remains to be learned about the timing of the various steps of oxidative ring formation (and hence the true nature of the enzyme-bound intermediates) and about the exact role of the enzymes involved in these late steps. As shown in Scheme 1, the

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• optimal experimental conditions already reported with triazines [22][23][24]. In chlorobenzene at 220 °C (optimal reaction temperature for six-membered-ring formation), the corresponding cycloadducts 10–13 were obtained in high yields (Scheme 4, Table 3). We therefore developed an efficient method for the

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• peroxide moiety, the Isayama–Mukaiyama peroxysilylation, and reactions involving peroxycarbenium ions. Syntheses employing hydrogen peroxide and the intramolecular Kobayashi cyclization are less frequently used. 1.1. Use of oxygen for the peroxide ring formation The singlet-oxygen ene reaction with alkenes

• -ene (148) (Scheme 35). The cyclization occurs selectively because the hydroperoxide group in intermediate 147 attacks only one of two possible electrophilic carbon centers [266]. 1.5. 1,2-Dioxolane ring formation through oxidation of the allylic position 1,2-Dioxolane-containing compounds 150a–d were

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• provide a steady tool for the ring formation of 4,4-spirocyclic γ-lactams with the incorporation of CO as a carbonyl group. Experimental Typical procedure for a construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with CO: A magnetic stirring bar, 2-(azidomethyl)-N-benzyl-N-(2

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• and molecule types have been used depending on the desired geometry, such as ring formation [9], carbohydrate–triazole conjugation [10], aryl–alkyne linked structures [11][12][13][14][15] and the use of DNA as a rigid bridge between silver nanoparticles and quantum dots [5]. Among the rigid linking

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• -annulation cascade reaction with N,N-(dialkylamino)benzaldehydes, a process in which a 1,5-hydride shift occurs followed by larger ring formation [16]. After the evaluation of different Brønsted acid catalysts, diphenylphosphate (20 mol %) was identified as a suitable catalyst for the reaction. Toluene again

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• transformations and easily separated after the cycloadditions. Whilst the cycloadditions described above demonstrate the preference for the dipolarophile installed at module 3, we then attempted to alter the cyclization mode (module 3→4) by increasing the entropic barrier for medium-sized ring formation (Scheme 4

• formation of a seven-membered ring. Despite the minor pathway, cycloaddition at module 4 also competed to give 54 in 22% yield. On the other hand, cycloaddition of 52 exclusively occurred with the indole group at module 4, giving rise to 56 in 94% yield without eight-membered ring formation leading to 55. X

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• δ-lactam ring formation) is irreversible, there are at least three possible explanations for the high diastereocontrol in the formation of 1a–j and 2a–l: - The first is that the nitro-Mannich step is highly diastereoselective and lactamisation occurs subsequently without any effect on the

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• -protection gave the alcohol 12 which was oxidized to aldehyde 8a. Cascade condensation, cyclization, cycloaddition The cascade tricyclic ring formation was then investigated with the aldehydes 6, 8a and 8b. Heating aldehyde 6 with glycine gave a mixture of unidentifiable products. However, heating with

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• responsible for uracil ring formation, although biochemical evidence is currently missing. The final hydroxylation step towards cylindrospermopsin has been shown to be catalyzed by CyrI, a 2-oxoglutarate-dependent iron oxygenase [31]. Interestingly, two epimers were described for the corresponding hydroxyl

• halogenated by unique biochemical mechanisms through the two non-heme iron(II)-dependent halogenases BarB1 and BarB2 (Figure 6A) [40]. Further extraordinary features of the pathway include one-carbon truncation during chain elongation, E-double bond formation and thiazole ring formation. Jamaicamide The

• substituent, a beta-methoxy eneone system, and a pyrrolinone ring [41]. The incorporation of the chlorovinylidene group was partially elucidated and predicted to be highly similar to the cyclopropane ring formation of curacin A biosynthesis (Figure 6B) ([42], see below). The enzyme cassette comprises a PKS

Intramolecular hydroamination of alkynic sulfonamides catalyzed by a gold–triethynylphosphine complex: Construction of azepine frameworks by 7-exo-dig cyclization

• Hideto Ito,
• Tomoya Harada,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2011, 7, 951–959, doi:10.3762/bjoc.7.106

• intramolecular hydroamination of alkynes [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], seven-membered ring formation is rare and is limited to the cases where the substrate is preorganized for cyclization: The substrates must

• triethynylphosphine ligand L1 was also evaluated for the eight-membered ring formation of sulfonamide 9, which is much more challenging than the seven-membered ring formation of 4. The reaction required 5 mol % catalyst loading under heating conditions (80 °C) in 1,2-dichloroethane for a reasonable conversion rate to

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• . Its synthesis, as well as that of its dihydroxylated homologue 36, features as the key step five-membered ring formation via RCM induced by the 2nd-generation Grubbs catalyst 5 (Scheme 6) [58]. A further contribution to new pyrrolidine-based azasugars, characteristically having 1,2-dihydroxyethyl side

Novel carbazole–pyridine copolymers by an economical method: synthesis, spectroscopic and thermochemical studies

• Aamer Saeed,
• Madiha Irfan and
• Shahid Ameen Samra

Beilstein J. Org. Chem. 2011, 7, 638–647, doi:10.3762/bjoc.7.75

• monomers. i) R–Br, 50% KOH, benzene, TBAB, 80 °C, 2 h; ii) AcCl, AlCl3, CHCl3, 0 °C then rt, 3 h. Synthesis of poly[3,6-N-alkylcarbazole-4-(3-substituted phenyl)pyridine-2,5-diyl]. i) CH3COONH4, CH3COOH, reflux, 18 h. Proposed mechanism of pyridine ring formation. Thermal data and molecular weights for

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• first results on the direct alkynylation reaction combined in a one-pot procedure with gold-catalyzed indole ring formation are promising, and analogous strategies combining palladium-catalyzed synthesis of indoles [3] and gold-catalyzed alkynylation could also be envisaged. The next step will be to