Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• carbon-substituted piperazines [19][20][21][22]. Mendoza et al. have developed a [3 + 3] dimerization of azomethine to synthesize highly substituted piperazines [23]. Notably, Stoltz and co-workers recently developed an enantioselective synthesis of piperazin-2-ones and piperazines using a palladium

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• group at the time had worked with cavitands. In fact, John was – to cut a long story short – instrumental to Don’s publications on the synthesis and properties of soluble carceplexes formed by the dimerization and covalent linking of tetrol-cavitands (Scheme 4). When I first arrived on the scene one of

• hydrophilic portal region, then dimerization of the host will not occur. For example the binding of charged amphiphiles such as n-octanoate lead to 1:1 complexes [33][34]. With these two points noted, a wide range of guests trigger dimerization to form the capsule with ostensibly sixteen negative charges on

• sterically hinder dimerization interfere less with an assembly as the angle between the two interfacing surfaces of a pair of cavitands increases from 0° (in a dimer) to ~70.5° (in a regular tetrahedron). This senary assembly many be higher in free energy, but because this container has a volume of four

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• buffer (pH 7.0). The tall peak eluting at 1.5 min in chromatogram C corresponds to either the enzyme itself or an impurity in the commercial preparation. Phosphitylation and subsequent dimerization of thymidine. Supporting Information Supporting Information File 54: Experimental methods, HPLC

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• bound substrate (Figure 25). Indeed, the exchange of this glutamate against an alanine residue resulted in an inactive version of the protein. Further an arginine residue, which could be involved in dimerization, was mutated to an aspartate. Also this mutant lost its catalytic activity, indicating that

• dimerization is essential [63]. The pseudopyronine synthase PyrS represents a homologue of PpyS. Using PpyS from Pseudomonas sp. GM30, it was analyzed if this KS is also involved in the formation of α-pyrones. The two pseudopyronines A (55) and B (56) have been up to now isolated from different Pseudomonas

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• -derived NHCs have found widespread application as catalysts for benzoin reactions, whereas triazolium-derived NHCs have emerged as popular catalysts for enantioselective benzoin transformations. Review Homo-benzoin reactions The homo-benzoin condensation constitutes an overall catalytic dimerization of an

• –Michael cascade. Divergent catalytic dimerization of 2-formylcinnamates. One-pot, multicatalytic asymmetric synthesis of tetrahydrocarbazole derivatives. NHC-chiral secondary amine co-catalysis for the synthesis of complex spirocyclic scaffolds.

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• were reported many years ago. Were the water-soluble tweezers we set out to prepare in 1985 ever made? Where does the field stand today? We found that our molecular tweezers are well preorganized for dimerization, limiting their use in water [22], whereas Klärner and colleagues discovered that their

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• the form of a Pd(I) dimer [13]. This suggests that Cp is more likely to undergo dimerization than Cin. CpDim was confirmed to be a poor catalyst under the conditions employed in Figure 2 (Scheme 5). This result is indicative of CpDim as an off-cycle deactivation product, which reduces the amount of

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• , the addition of amino additives such as pyridine, morpholine, Et3N or DBU was shown to be detrimental to the G-HII-catalyzed dimerization of styrene (Table 2). Moderate to poor yields in stilbene 7’ were obtained and the value of the yields was correlated with the pKa of the couple ammonium/amine. An

• recommended to avoid dimerization. The most studied strategy allowing the use of olefins bearing N-heteroaromatics is the formation of the N-heteroaromatic salt prior to metathesis. The salt can be either isolated before metathesis or formed in situ using acidic additives. Alternatively, introduction of bulky

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• -functionalized arene dimerization [37]. Besides the issue of selectivity, another major challenge in the DG-assisted C–H activation lied in the removal of the DG, which undermined the efficiency of the synthetic procedure. To alternate the hardly removable DG of the pyridine ring, Carretero and co-workers [38

• related C–H transformation by providing key haloarene intermediates. For examples, in the CuI-catalyzed cross arene dimerization reactions reported by Daugulis et al., the in situ formation of iodoarene intermediate was discovered as the indispensable step during the generation of the biaryl products [65

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• . Mass spectrometry analysis was performed on a Q-Exactive mass spectrometer (Thermo Scientific). The Benesi–Hildebrand equation [59] was used to find association constants while the method proposed by Tan [60] was used for dimerization of 1. It was assumed that 1:1 stoichiometry is present in all

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• secondary structures from aromatic backbones driven by different noncovalent forces (including hydrogen bonding, donor–acceptor, solvophobicity, and dimerization of conjugated radical cations) and solution-phase supramolecular organic frameworks driven by hydrophobically initiated aromatic stacking in the

• cavity of cucurbit[8]uril (CB[8]) are highlighted. Keywords: donor–acceptor interaction; foldamer; hydrogen bond; radical cation dimerization; supramolecular organic framework; Review Childhood and growing up I was born on July 23rd, 1966 in the small, remote village of Fang-Liu (a combination of two

• . In 1998, the group reported the extremely stable quadruple hydrogen-bonded dimers 8·8 [16] (Scheme 4). By using an 1H NMR dilution technique, a lower limit to the dimerization constant Kdim (>107 M−1) was estimated. Professor Zimmerman hoped to make an accurate determination of the binding stability

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• (18). Citrinamine A (1) is the 2,2´-didebromo derivative of mauritiamine (7) and as in the original publications of 7 and 18 no chiroptical effect was observed for 1. Synthetic studies on mauritiamine (7) [14] demonstrated the formation of similar racemic products by a chemical oxidative dimerization

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties

• Laura G. Sarbu,
• Lucian G. Bahrin,
• Peter G. Jones,
• Lucian M. Birsa and
• Henning Hopf

Beilstein J. Org. Chem. 2015, 11, 1917–1921, doi:10.3762/bjoc.11.207

• The Cambridge Crystallographic Data Center via http://www.ccdc.cam.ac.uk/data_request/cif. The desulfurative dimerization of 1,3-dithiol-2-thione 6 was effected by heating it with trimethyl phosphite at 100 °C (Scheme 2). Purification of the crude reaction mixture by column chromatography resulted in

• isolation in order to investigate their structural and chiroptical properties. Conclusion The synthesis of as yet inseparable isomeric tetrathiafulvalenes has been performed by desulfurative dimerization of a [2.2]paracyclophane-substituted trithione. The latter compound was obtained from the corresponding

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

• dimerized 16-membered ring product 101 in 57% yield, which was generated by a RRM–dimerization sequence and its monomer 100 in 14% yield along with 99 in 26% yield (Scheme 20). Bicyclo[2.2.1]heptene derivatives Holtsclaw and Koreeda [25] have explored a chemoselective RRM of the enone containing norbornene

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• worse than nG-SIPr. As outlined in Table 2, all tested catalysts were similarly effective in CM of methyl undecenoate 12 with cis-1,4-diacetoxy-2-butene (13), but parent dichloro complexes provided smaller quantities of dimerization product of 12. In CM of 12 with electron deficient methyl acrylate 15

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

• -configuration were formed by SmI2-mediated reductive dimerization of a 4-(indol-6-yl)butenone, obtained by Heck reaction. The two indolyl units appear to chelate Sm(II)/(III) leading to a gauche-type arrangement at the newly formed bond between the two β-carbons. Through a sequence of Sonogashira cross coupling

• plants [1][2][3] and also in fungi [4] and myxobacteria [5][6]. One example is raputindole A (1), isolated in 2010 from the Rutaceous tree Raputia simulans Kallunki [1], which exhibits a unique tetrahydrocyclopenta[f]indole partial structure (Figure 1) probably formed by dimerization of (E)-6-(3

• their reductive dimerization. We also describe the synthesis of the antimicrobial natural product indiacen B (2) from the myxobacterium Sandaracinus amylolyticus [5], bearing a unique isoprene moiety chlorinated at the methylene group. Results and Discussion SmI2-induced reductive dimerizations 6

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• showed two reversible two-electron redox waves at −0.03 and 0.38 V vs Fc/Fc+ in benzonitrile under normal conditions [25][60]. Conducting nanostructure formation from star-shaped oligo-TTFs Although pristine TTF does not self-associate in solution due to the low association constant for dimerization, the

• tris(TTF)[18]annulene 32. Star-shaped TTF oligomers 38–43. Pyridazine-3,6-diol-TTF 45 and its trimer 46. Redox potentials of 16–19 and absorption maxima of monocations 16•+, 17•+, 18•+ and 19•+, and dications 162+, 172+, 182+ and 192+ [25][59]. Association (dimerization) constants and thermodynamic

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• in the total loss of photopyrone production (Figures S1 and S2, Supporting Information File 1). Similarly, no photopyrone was produced in a R121D derivative. R121α is predicted by the model to be located at the dimer interface interacting with D137β. Thus, dimerization shown to be essential for KS

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

• was subjected to dimerization involving cross-metathesis with G-I/G-II/Schrock catalysts which generated the cyclized product 154. Subsequently, hydrogenation of the cyclophane 154 followed by minor functional group modification gave the natural products 155 and 156 (Scheme 23). Furthermore, the same

• 171 via RCM/CM using G-I (12) or G-II (13) under high dilution conditions to obtain the [n], [n,n] and [n,n,n]paracyclophanes 172–174. Compounds with a short alkenyl chain gave mainly [n,n] and [n,n,n]paracyclophanes (173 and 174) by a dimerization or trimerization sequence. When the compound has a

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• reduction of the nitro group to oximes would be favoured. On the other side the electrolyte should not be aprotic as protons are required for protonation of the intermediate anions in the reductive dimerization (Scheme 1). According to the proposed mechanism for the cathodic hydrodimerization the radical

• anion b formed by one electron reduction of the substrate a, has three pathways for dimerization [1][2]. In path (I) protonation followed by one-electron reduction leads to anion c, which in a Michael addition with substrate a forms the anion d, which is protonated to hydrodimer f. In path (II) b

• in [6][7][8]. There have been reports on the reductive dimerization of nitro alkenes prior to 1991. 1,4-Dinitro-2,3-diphenylbutane (3) has been obtained in less than 20% yield in the catalytic hydrogenation of β-nitrostyrene (4) [11]. Hydrodimerization of 4 was observed in enzymatic reduction [12

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• by an electrochemical simulation program (DigiElch 7) involving an electrochemical mechanism (Scheme 4) composed by three one-electron processes and two charge-coupled chemical reactions (i.e., formation of mixed-valence and dimerization via a square scheme). Due to the equivalence of the two TTF

• bulky groups at the periphery of the TTF moieties does not provide an advantage for the self-assembly of dimers. Moreover, this dimerization phenomenon which is driven by the inclusion of one sidewall into the cavity of the opposing clip is not observed in the solid state for clips 2 and 3 (Figure 8

Carboxylated dithiafulvenes and tetrathiafulvalene vinylogues: synthesis, electronic properties, and complexation with zinc ions

• Yunfei Wang and
• Yuming Zhao

Beilstein J. Org. Chem. 2015, 11, 957–965, doi:10.3762/bjoc.11.107

• oxidative dimerization reaction of corresponding dithiafulvene (DTF) precursors [27]. This straightforward C–C bond forming reaction has not only allowed TTFV derivatives with different substituents to be readily assembled, but served as an effective methodology to construct the π-conjugated frameworks of

• ]. This olefination reaction went completion within 3 hours to give DTF 4 in 77% yield after column separation. Compound 4 was then subjected to an oxidative dimerization in CH2Cl2 at room temperature using iodine as oxidant. The dimerization gave TTFV 5 as a stable yellow solid in 80% yield

• generated on the electrode surface via the DTF dimerization reaction [15][16]. In the following scan cycles, the redox wave pair characteristic of TTFV at Epa = +0.62 V and Epc = +0.54 V was found to gradually increase in intensity as a result of increasing electrochemical dimerization. The same

Interactions between tetrathiafulvalene units in dimeric structures – the influence of cyclic cores

• Huixin Jiang,
• Virginia Mazzanti,
• Christian R. Parker,
• Søren Lindbæk Broman,
• Jens Heide Wallberg,
• Karol Lušpai,
• Adam Brincko,
• Henrik G. Kjaergaard,
• Anders Kadziola,
• Peter Rapta,
• Ole Hammerich and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2015, 11, 930–948, doi:10.3762/bjoc.11.104

• generated for the dication of both of these compounds, which signals intramolecular interaction of the two polaronic TTF units as we exclude π-dimerization since the EPR inactivity did not depend on the concentration of the species. A non-negligible interaction between the polaronic states was observed for

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• , is highly conserved [50]. Six of the seven cysteine residues Cys14/Cys79, Cys47/Cys113, and Cys43/Cys111 form intramolecular disulfide bonds to stabilize the monomer, whereas the seventh cysteine (Cys78) contributes to the formation of an intermolecular bond between the two monomers for dimerization

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• glycothymine branches in 13 and 14 are sterically more hindered than the thymine branches in 7 and 8. Again UV–vis spectroscopy further underlines the dimerization success as the absorption maximum at 270 nm disappears and mass spectrometry supports intramolecular photocycloaddition only (cf. Supporting