Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• experiment in which 3/4 was treated with Bu3SnH resulting in nucleoside 6 as the only observed product (Table 1, entry 4). The S-configuration at the 5’-position of nucleoside 6 could be explained by a Felkin–Ahn transition state with the hydrogen radical attacking from the less hindered exo-face [41][42

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• theoretical methods [52]. Their results are in agreement with the catalytic cycle presented in Scheme 1. However, the question is raised whether the bicyclic Diels–Alder species II is a real intermediate or rather a transition state of a concerted formation of the dihydropyridazine intermediate III directly

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• was calculated using transition state theory: ΔG‡ = −RT·ln(k/(kBT/h)), where k is the rate constant, kB is the Boltzmann constant and h is Planck’s constant. Second order rate constants were converted to pseudo-first order rate constants using an estimated physiological concentration of substrate

Dispersion interactions

• Peter R. Schreiner

Beilstein J. Org. Chem. 2018, 14, 3076–3077, doi:10.3762/bjoc.14.286

• but it is certainly attenuated [8]. We are still in the process of understanding just by how much. LD is a driving force for molecular aggregation that plays a key role in the thermodynamic stability, molecular recognition, chemical selectivity through transition-state stabilization, protein folding

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• concerted transition state that circumvents the formation of the 14e intermediate II, i.e., I–III, is higher in energy than I–II and II–III by 3.6 and 4.3 kcal/mol for systems 3 and 5, compared to 1, respectively. The unsaturated systems do not follow a concerted mechanism either, being 4.3 kcal/mol higher

• in energy for system 2. Overall, for all substituted indenylidenes this concerted transition state I–III is confirmed to be higher in energy. The structural analysis included in Table 2 supports the fact that the substituted indenylidenes display similar characteristics whatever the substituents are

• and 6 is that the next energy barrier for transition state II–III is larger, since the entering olefin requires a 90° rotation, and this is partially impeded when the phenyl group is substituted. However, the substituted indenylidene facilitates overcoming the energy barrier of the next transition

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• the main difference with the known reaction [51] between the hydrazides 3 and the phthalaldehydes in which two diasteroisomers have been observed. If the amino acid residue (R on the Scheme 5) enough implicates steric hindrance with the carboxyaromatic part of B, the pathway with disfavored transition

• state becomes unlikely and then the selectivity is important. Our model is in agreement with the diasteroisomeric ratio results. In fact, a total diastereoselectivity was observed, including 5d (R = Ph) since an epimerization of the initial asymmetric center was observed, therefore racemic trans-isomers

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• Chauvin [2]. Right: Potential influence of the protein as second coordination sphere in the transition state that lead to different metathesis products. (i) Ring-opening metathesis polymerization (ROMP), (ii) ring-closing metathesis (RCM) and (iii) cross metathesis (CM). Biotinylated GH-type catalysts for

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• conducted providing insights into motifs granting selective PqsD inhibition [52]. In a ligand-based approach, nitrophenylmethanol derivatives were identified as fragment-sized inhibitors of PqsD. Initially, these compounds where designed as transition state analogues mimicking the tetrahedral reaction

• line with the initial transition state analogue design principle. Further structural exploration of this class showed that this fragment-like size helps to retain cellular activity [56]. While fragment growing could increase target activity to the nanomolar range, a complete loss of efficacy in the P

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• (e.g., 24) function as PqsD transition state analogues, and were shown to inhibit the enzyme and reduce bacterial biofilm formation [75]. Numerous approaches target the signal molecule receptor PqsR, and compounds such as 25, 26 and 27 successfully inhibited virulence factor production, biofilm

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• conclusions about the order of substitution. Also, the observed selectivity in the case of ortho-methoxyphenylboronic acid suggested an additional metal O-chelation effect in the transition state, apparently not present in the ortho-chloro analogues. The rotational barrier in selected atropisomers was

• the transition state what causes that isomer (anti)-8 is formed in a smaller amount. The oxygen atom may serve as an extra ligand. Therefore, the coordination by the methoxy group to palladium may cause changes in the geometry of the complex, reflected in the atropisomers distribution. A similar

• , both in ortho-methoxyphenyl and ortho-chlorophenyl series (Figure 5 and Figure 6). In the former one, however, the successive arylation is additionally affected by apparent O-chelation of the metal at the transition state which results in noticeable diastereoselectivity of this process, leading to a

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• forms cobalt enolate J2, which converts into J3 by the addition of aldehyde via a chair transition state in a diastereoselective manner. Finally, protonolysis affords product 62 and regenerates the active Co(III)Cp* catalyst for the next cycle. Later, Li et al. reported a Co(III)-catalyzed

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• product in twist conformation. Due to the fact that the lower energy level of the chair conformation compared to the twist conformation is already present in the transition state the generation of the twist conformer is kinetically disfavored [39][40]. This kinetic phenomenon is sometimes called the Fürst

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• supramolecular host–guest interaction with the calixarene to form a stable transition state A. Then, another hydrogen bond is formed between the nitrogen atom of the tertiary amine group in A and acetylacetone in its enol form, leading to the formation of a ternary complex B. Finally, nucleophilic attack of

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• purpose is to determine or verify preferred reaction pathways. Oxidative addition of 4-bromoanisole to complex 17d proceeds by the C–Br bond activation to form a weakened Pd···Br bond, of 3.104 Å length in transition state (TS1), which ultimately results in a new Pd–Br bond, of 2.605 Å length (IM1

• is a stable intermediate between the reactants and the transition state (TS1). Thus, when the energy of the transition state is lower than the energy of the reactants or intermediates from which the transition state is formed it means there is a stable intermediate between them. Nonetheless, such a

• relatively low energy barrier indicates that the reaction proceeds at a fast rate in getting to the intermediate (IM1), thus it is kinetically favoured. The reaction then proceeds via transition state TS2, leading to the cleavage of the C(sp2)–Br bond and the formation of a new Pd–C(sp2) bond, to form a cis

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• and studied oxazoline synthesis. Experimental The calculations have been performed using the Gaussian 09 program package [46]. The M06 exchange–correlation functionals have been employed to solve the Kohn–Sham equations [47]. For the geometry optimisations, transition state searches and vibrational

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• was proposed to proceed via the formation of the transition state 73 to avoid steric interaction between the R group of the aldehyde and the SMe of the toluene precursor, hence, led to anti selectivity. The biocatalytic reduction of α-sulfenyl-β-ketoesters 74 using Baker’s yeast was reported by

• presence of the hydroxy functional group acting as a transition-state analog. The synthesis of the inhibitors commenced with the conversion of aldehyde 127 into alkene 128 via a Wittig reaction followed by epoxidation to furnish epoxide 129. Regioselective opening of the epoxide ring with a thiolate gave

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• chemical transformations. Presumably due to attractive dispersive interactions between two adamantyl groups in the transition state of a [4 + 2] cycloaddition of benzynes (Scheme 1), the seemingly sterically more hindered product is formed preferentially [8]. Similar to other noncovalent interactions [9

• a step-wise fashion. A similar mechanism has previously been described by McMullin, Williams, and Frost [38], as well as by Ackermann [39][40] for ruthenium-catalyzed C–H alkenylations. In the first transition state (TS1a, Figure 2), the κ2-coordination of the acetate ligand changes to a κ1

• stabilizing nature of these interactions. In the second transition state TS2a (Figure 2), the C–H bond is broken and the proton is transferred to the acetate which results in the formation of the cobaltacycle 7a. Acetic acid dissociates, and N-cyano-N-phenyl-p-toluenesulfonamide (2a) coordinates to the 16

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• transition state C of the carbocobaltation step (Scheme 11), facilitating the further selective formation of the branched allylcobalt species D which could be converted into the thermodynamically more stable (E)-allylcobalt species E because of the flexible C(vinyl)–C(allyl) single bond. The generated

• compound E then undergoes transmetalation with the chromium salt to give the (E)-allylchromium species F. In contrast, the carbometalation of a simple allene produces (Z)-allylcobalt species E′ and the corresponding (Z)-allylchromium product F′ would be provided through a transition state such as C′, in

• chromium to afford I and the highly nucleophilic allylchromium species J, which retains the same stereochemical information on the olefinic moiety as that of H. The allylchromium species J reacts with the aldehyde 3 at the γ-position of the allyl metal unit via a cyclic six-membered transition state K to

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• sodium cation plays an important role in making the sodium enolate soluble in organic phase and this leads to enantiofacial differentiation in the transition state [39]. Just recently, Neri et al. utilized the cation recognition abilities of calixarene-amides in phase-transfer catalysis [40]. Seven

• major diastereomer with moderate yield but the selectivities were low. Acetone (94) was also used as substrate but only 40% ee was obtained although the yield was 80% (Scheme 26). In order to create a more compact transition state and increase the selectivity by this way in direct stereoselective aldol

• and water molecules led to formation of hydrophobic and hydrophilic regions. This in situ-formed system enhanced the activity and selectivity of catalyst 92. The Houk–List transition state model was suggested to account for the observed high selectivity. Just recently, design and synthesis of a series

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• -phenylsydnone and DMAD was first studied by Huisgen and Gotthardt [54] in p-cymene at 90–110 °C. They found the cycloaddition to be overall second order and its activation entropy ΔS≠ = −130 J·mol−1·K−1 showed association character of the rate-limiting step with a relatively tight transition state. Moreover

• , for the cycloaddition of the structurally similar ethyl phenylpropiolate in various solvents only a small decrease of the bimolecular rate constant with increasing solvent polarity (in terms of relative permittivity) was observed excluding a transition state having a polarized character. Finally

• intermediates (cf. Scheme 5) with a negligible charge transfer flowing from sydnone to the alkyne. This result suggests that there should be a very low influence of the substituents polar effects on the energy of the transition state. Moreover, energy gaps between the dipole HOMO and the dipolarophile LUMO or

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• deprotonation of the imidazolyl group to give betain A, which binds to a Cu(I)-OTf fragment leading to complex B. Next, the aryl group is transferred from the iodine to the copper atom leading to the Cu(III) complex D via a five-membered transition state C. Reductive elimination through transition state E

• , the intact 2-iodoaryl group is transferred via presumed transition state TS1, which leads to a good AE (50% for 22a) and allows the further transformation of the α-arylation product 22 via cross coupling reactions. In addition, the in situ generation of the PIFA reagent proved viable, in order to

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• plausible mechanism and transition-state model 27 for the formation of the major isomer through the attack of the carboxylic acid group to the ipso position of the naphthol ring from the less sterically hindered Re-face of the substrate 25. It is worth mentioning that very recently they have introduced a

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• formation (Scheme 1) was discovered by Oh and co-workers in 1988, and although it was based on previous work by the Ochiai group, the paper was the first to suggest a six-membered transition state indicative of a Claisen reaction [6][7]. In 1991, Ochiai and co-workers coined the phrase reductive iodonio

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• transfer and metal ion binding, for stabilization of transition states may be elucidated and systematic variation of the basicity of the entering or departing nucleophile enables determination of the position of the transition state on the reaction coordinate. Such data is important on analyzing enzyme

• , for stabilization of transition states may be elucidated and systematic variation of the basicity of the entering and departing nucleophile enables determination of the position of the transition state on the reaction coordinate. Such data is important on analyzing enzyme mechanisms based on

• proceeds via a pentacoordinated species having the structure of a trigonal bipyramid. In case this species represents an energy maximum on a single barrier energy profile, as with SN2 displacement at carbon, the reaction is called concerted and the pentacoordinated species is a transition state. The

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• intermediate or a transition state depending upon the accumulation of the positive charge on the sugar ring (Figure 2). As a result, any change in the nucleobase–sugar connectivity (C–N) affects the formation of the oxocarbenium ion and thus influences the stability (or instability) of the nucleoside analogues

• approach of the nucleophile determine charge accumulation on the sugar ring. A concerted process leads to a transition state-like species shown in the figure, while a greater accumulation of positive charge leads to an oxocarbenium ion intermediate. Structural modifications to nucleobase-sugar connectivity