Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• coordination to Ni. The complex B regenerates after the conjugate addition via transition state C and coordination of a new β-ketosulfone molecule to Ni. TS1 and TS2 are proposed by analogy with 1,3-dicarbonyl compounds [47] to rationalize the asymmetric induction. As illustrated in Scheme 2, β-ketosulfone is

• nitroalkene in TS2-I and 2-II may also help to rigidify the transition state and improve the stereoselectivities. The observed (2R,3S)-diastereoselectivity in the presence of catalyst 7a stems from the addition of the Re face of the β-ketosulfone to the Si face of the nitroalkene in TS2-I. We suppose that the

• -Michael reaction of (2R,3S)-8a in chloroform-d solution. ORTEP diagram of (2R,3S)-8d. The proposed mechanism of asymmetric addition of β-ketosulfones to nitroalkenes. Transition state models for asymmetric addition of β-ketosulfones to nitroalkenes. Screening of Ni(II) complexes with chiral diamines in

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• formal syn-SN2’ reaction. This is an intriguing observation, since for other TSs a NPP-cyclisation by anti-SN2’ is usually described [40][45][46][47]. This cyclisation mechanism is thought to be the predominant case, giving rise to a more energetically favoured transition state, but occasionally also the

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• package [26]. The energies of all the structures are on the B3LYP/6-311G++(d,p) level, and the zero-point vibrational energy (ZPVE) corrections are all at the DFT level. Throughout this study, all the relative energies refer to the ZPVE-corrected energies. For the transition state (TS) between species A

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• 1,2-di(pyridin-4-yl)ethylene and 4,6-dichlororesorcinol in the transition state (Figure 24). Finally the cyclobutane derivative 43 was observed after the release of catalyst for the next cycle. In 2012, again the MacGillivray group reported an improved version of the above mentioned [2 + 2

• –tert-butylcalix[4]azulene through mortar and pestle grinding of the host and the guest. The structure of the complex was obtained from DFT study. Formation of a 2:2 complex between the supramolecular catalyst and the reagent in the transition state of the [2 + 2]-cycloaddition reaction of 1,2-di

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• dry dichloromethane resulting in the stereoselective formation of the corresponding β-isomer 17 of O-ethyl nicotinate riboside in high yield. It was speculated that less polar solvents, such as DCM, contribute to the formation of a less dissociated transition state, similar to F in Figure 3 above

• metal complex. The amide functionality in the 3-nicotinamide core plays a crucial role in the subsequent reduction because it coordinates with the metal center of the hydride complex, resulting in a favorable transition state which ensures the transfer of the hydride on the 4-C position of the

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• –base equilibrium, leading in situ to the formation of its conjugate base 8. This anionic intermediate 8 acts as nucleophile and reacts with bromoethane (9) in a, probably, bimolecular mechanism, through a pentacoordinate transition state 10 as represented in Scheme 2. The reaction occurs in a

• . Table 4 illustrates the optimized geometry for the transition states for each possible reaction path. The comparison of the two possible reaction paths shows that although N-ethylation of the carboxamide site is associated with a lower energy barrier, addition of solvent stabilizes the transition state

• optimized geometries provided the expected 180° angle for nucleophilic bimolecular substitution. In this regard, the transition state of the reaction with the carboxamide conjugate base provided a value of the N–C–Br bond angle about 2o greater than that of the reaction with the oxoquinoline anion, in all

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• , which is opposite at C2, was assigned by comparison of their computed and experimentally observed CD spectra [33][34]. To tentatively explain the observed stereochemical outcome in the absence of additional knowledge on the transition state of the rearrangement [36], two reactive conformers G and G

• of an aryl group at C4 but no additional details were provided. The high diastereoselectivity was explained by considering a six-membered chair-like cyclic transition state model TS3 in which the substituent at the α position of the ester (C4) preferentially occupies a pseudo-equatorial position

• nature of the rearrangement (Scheme 10) [33][34]. The acidic promotor may be simply assisting the dissociation of the C4–O bond in the transition state TS3 whilst an aromatic group (R1 = Ar) would contribute to the stabilization of a developing positive charge at C4. The [3,3]-sigmatropic rearrangement

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• energies are (Ea) in kcal mol−1 and italic. Transition state leading to 8eq following front1 attack (Ea = 32.6 kcal mol−1, Figure 5, Table 3, entry 1). Breaking and forming bonds in dashed lines, additional C–H-interactions with dotted lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d) at 298 K

• ). Transition state leading to 8ax following front2 attack (Ea = 33.2 kcal mol−1, Figure 5, Table 3, entry 2). Breaking and forming bonds in dashed lines, additional C–H-interactions with dotted lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d) at 298 K). Transition state leading to 8eq following

• side attack (Ea = 37.4 kcal mol−1, Figure 5, Table 3, entry 3). Breaking and forming bonds in dashed lines, additional C–H-interactions with dotted lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d) at 298 K). Transition state leading to 9 following side attack (Ea = 31.4 kcal mol−1, Figure 5

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