Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• further demonstration that cyclization to isochromanone would be favored with respect to benzofuranone from the reaction of compound 2c with 12a. In this case both substrates bear an ester functionality and in principle both six- and five-membered rings could be obtained. Unexpectedly, upon exposure to

• , selective synthesis of benzo-fused six- or five-membered rings can be achieved. We have demonstrated that the 5-membered ring formation is favored, when the two processes are competitive, and we have also shown that acetonitrile can act as a third component in the cyclization to oxazepinones. By employing

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• natural products, have been used as chiral phase-transfer catalysts [12][13]. Bicyclic guanidines with five-membered rings are also known from the alkaloid isoalchornein [14][15]. In subsequent years, synthetic compounds (6–9) of this structural type have been developed as chiral Brønsted bases [16][17

• the chiral TBD analog 10. The cyclization steps in particular, which convert the triamine 19 into the final guanidine 10, give considerably higher yields compared to guanidines with five-membered rings such as compounds 6–9. Apart from the better synthetic accessibility the formal ring expansion to

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• cis/trans assignments, common wisdom [5] commends the simple criterion that three-bond NMR coupling constants (3JH,H) should be more positive for a cis than for a trans relationship of the vicinal, sp3-positioned protons in five-membered rings. Indeed, cis-1,2-dibromoindane displayed 3J(1-H,2-H) = 5.0

Direct estimate of the internal π-donation to the carbene centre within N-heterocyclic carbenes and related molecules

• Diego M. Andrada,
• Nicole Holzmann,
• Thomas Hamadi and
• Gernot Frenking

Beilstein J. Org. Chem. 2015, 11, 2727–2736, doi:10.3762/bjoc.11.294

• ones. The X–Ccarb–X (X = N, C, O and S) angle in the five-membered rings slightly varies between 99.6° (10) and 105.6° (15) and is slightly larger (120.1°) in the acyclic carbene 5. This angle is often associated with the σ-donor properties which are related to the spx hybridization of the carbene lone

Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• in the five-membered rings) are minor for electron-deficient 4d lying below 5°, whereas they are much larger in electron-rich derivatives, where they reach 20.45° in 4a, 13.58° in 4b and 11.23° in 4e. This observation corresponds well with previously reported data: the electron-deficient N-Ts

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• displays crystallographic inversion symmetry, although the true symmetry is close to C2h (rmsd 0.03 Å). The central C–C bond seems slightly short at 1.520(2) Å, but a similar value of 1.523(5) Å was observed in the only other known system with two analogous five-membered rings joined by a –CH2–CH2– moiety

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• (Scheme 4) suggest a neighbor-group effect through an O-lp donor to σ*P–Cl acceptor interaction, supporting chloride substitution (Figure 5, Scheme 4). Hypervalent P(III)–O interactions with similar P–O distances are documented for five membered rings [47][48] as well as for acyclic systems [49]. The

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

• the opposite face to H-8 further suggested this. Further analysis of the conformations of 7a and 7b was achieved by examination of the coupling constants in the furo[2,3-b]chromene ring. The use of coupling constants to determine stereochemistry in five-membered rings is often extremely difficult, due

Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

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

Beilstein J. Org. Chem. 2014, 10, 2021–2026, doi:10.3762/bjoc.10.210

• case. Conclusion In summary, we have demonstrated in this study that aldol-type condensations constitute an attractive alternative to prepare [2.2]paracyclophane derivatives with annelated (and functionalized) five-membered rings, making these derivatives easily available for further transformations

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ease of preparation via IMCRs [27][28][29]. First, the β-lactams will be described followed by five-membered rings varying from pyrrolidines to tetrazoles based amide bond isosteres. Examples of the six-membered rings showing peptide like-properties are the piperazines, homoprolines, dihydropyrimidones

Cyclic phosphonium ionic liquids

• Sharon I. Lall-Ramnarine,
• Joshua A. Mukhlall,
• James F. Wishart,
• Robert R. Engel,
• Alicia R. Romeo,
• Masao Gohdo,
• Sharon Ramati,
• Marc Berman and
• Sophia N. Suarez

Beilstein J. Org. Chem. 2014, 10, 271–275, doi:10.3762/bjoc.10.22

• cations have greater thermal stability than the ammonium ones. One trend observed for both cation types is that the ILs with five-membered rings have greater thermal stability than those with six-membered rings. Further work will be required to determine if the observed TGA behaviors are due to actual

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• transpires that this C–F…N+ interaction is a general effect which has also been observed in larger N-heterocycles, as discussed below. 3.2 Five-membered rings The C–F…N+ interaction can have a more dramatic impact on the conformations of pyrrolidines, since they are inherently more flexible than azetidines

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. Keywords: heterocycles; medicinal chemistry; pharmaceuticals; six-membered rings; synthesis; Introduction The commonality of six

• -membered rings, which allowed us to analyse how medicinal chemists have addressed challenges over the past 30 years [7]. This work not only represents an overview of the various chemical transformations employed, but also allowed us to judge whether and to what extent new ideas and concepts have been

• construct modern pharmaceutical structures a general overview of the most valuable synthetic techniques and best working practices as used by the pharmaceutical industry can be constructed. Previously, we reviewed the most common synthetic routes to the top-marketed drugs containing heterocyclic five

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• by the spiro connection of the three- and the five-membered rings. Following these rules, a Möbius type coarctate fragmentation with two five-ring terminators (10 electrons) should proceed as a photochemical reaction, and a corresponding fragmentation with a seven- and a five-ring (12 electrons

Conformational analysis and intramolecular interactions in monosubstituted phenylboranes and phenylboronic acids

• Josué M. Silla,
• Rodrigo A. Cormanich,
• Roberto Rittner and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2013, 9, 1127–1134, doi:10.3762/bjoc.9.125

• -fluorobenzoic acids [17]. Recently, OH∙∙∙F hydrogen bonds were found to be difficult to operate in monocyclic compounds when forming five-membered rings, because of geometric restrictions imposed by the rigid rings [18]. In the present work, 2- and 4-fluorophenylboronic acids were analyzed by using theoretical

• 1a and 1b relative to 2a. Conformer 1c was found to be stabilized by a nonbonding F∙∙∙O interaction, which contributes to the formation of pseudo five-membered rings. This would be possible because of an nF→π*CC interaction (Figure 3), which contributes to a resonance structure with positive fluorine

• ability of halogens to participate in hydrogen bonds forming four- and five-membered rings. However, 6a, 7a and 8a, the most stable conformers for the respective compounds, exhibit dihydrogen bonds, with electronic densities ρ(r) superior to that found for 1b. Moreover, nX→π*CC interactions are also

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• the fabulous Pauson–Khand reaction [10][11] to introduce simultaneously the two adjacent five-membered rings. Outlined in Scheme 2 is a very short total synthesis of (±)-13-deoxyserratine (11) [12][13]. The first two of the four rings in 11 are again created through the powerful Pauson–Khand reaction

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• and heterocycles, with a high degree of regio- and stereoselectivity in the formation of five-membered rings, although its application to larger rings is still not general. The present review will survey some recent advances in the application of inter- and intramolecular enantioselective

• , the aryllithium intermediate undergoes a tandem carbolithiation–γ-elimination leading to enantioenriched 2-cyclopropylphenols [51]. As shown, these enantioselective intramolecular cyclizations are mostly employed for the formation of five-membered rings. The 6-exo cyclization of an aryllithium

• . Enantiomerically enriched five-membered rings can be prepared through intramolecular carbolithiation reactions of unsaturated aryllithiums in the presence of chiral ligands. The application to the formation of six-membered or larger cycles with the same degree of stereo- and regiochemical efficiency has not been

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• substance class in organic chemistry containing nitrogen and three fused five-membered rings [1][2][3]. Due to the unique rigid bowl-shaped structure with one noninversible electron lone pair at the bottom of the central nitrogen (“centro-N”) atom, 10-azatriquinane analogues are used as efficient chelation

• established that the reduction product 5a (Figure 3) was formed with a rigid 10-heteroazaquinane skeleton through an intramolecular Lewis acid–base pair interaction [15][16][17][18]. Three five-membered rings are fused to give a very stable bowl-shaped tricyclic system with five stereogenic centers

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• fulvenes are produced as side products [25]. The formation of fulvene derivatives and other compounds containing five-membered rings has often been noted in this type of approach [26]. These cyclic products are formed by mechanisms involving carbene (generated during the dehalogenation step of the

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• chirality, directed through the coordination sites D in complex 5 and B in 6, and the corresponding adjacent methylenes of the chelating five-membered rings. The second, newly created element of chirality may be provided by steric repulsive interactions in the arms BA/DE, which will twist the six-membered

Stereogenic boron in 2-amino-1,1-diphenylethanol-based boronate–imine and amine complexes

• Sebastian Schlecht,
• Walter Frank and
• Manfred Braun

Beilstein J. Org. Chem. 2011, 7, 615–621, doi:10.3762/bjoc.7.72

• and 10. This becomes evident from Figure 2, which shows a superposition of the skeletons of complexes 8 (red) and 10 (green). As a consequence of the saturation and the rehybridization at nitrogen, the five-membered rings are connected in a more concave, folded manner in the amine complex 10 than in

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• representative chemical entities the examples discussed have been selected from the top 200 best selling drugs of recent years. Keywords: five-membered rings; heterocycles; medicinal chemistry; pharmaceuticals; synthesis; Introduction Over the past few decades organic chemistry has seen tremendous progress and

The tert- amino effect in heterocyclic chemistry: Synthesis of new fused pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives

• Dipak Prajapati and
• Kalyan Jyoti Borah

Beilstein J. Org. Chem. 2007, 3, No. 43, doi:10.1186/1860-5397-3-43

• on the nature of A = B. The first path (a) involves ring closure between the ortho-substituent and the tert-nitrogen atom. The second path (b) comprises those reactions which involve one of the α-methylene groups attached to the atom A, ultimately leading to the formation of five membered rings. The