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

• media considered, the N–C–Br bond angle (α) on the transition states were slightly higher for the carboxamide group (Table 3). These results are consistent with the one previously found. As already shown, the oxoquinoline conjugate base is more stabilized when compared to the carboxamide one. Such

• . 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

• . Since experimentally, this is not observed, it can be concluded that only the N–H site of oxoquinoline undergoes deprotonation. That is, the conjugate base of the carboxamide is not generated in the process. Observing the predicted N–C–Br (α) angle in the calculated transition states, none of the

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

• ’ were considered which would lead to five-membered ring transition states in which the aryl group occupies a preferential pseudo-equatorial or a less favorable pseudo-axial orientation, respectively (Scheme 3) [33][34]. The authors also showed that phosphine oxide (E)-3f could be reduced to the

• leading to zwitterronic intermediates 8 and 8’. This would result in an increase of conformational flexibility thereby facilitating the nucleophilic displacement of the ammonium by the phosphinite through transition states TS1 and TS2 (SN2-type process), respectively. Oxaphospholanium zwitterions 9 and 9

• activation barriers of the reactions leading to 8 and 8’, regardless of the aromatic substituent. Since 8 and 8’ were in rapid equilibrium with phosphinite 6, the diastereoselectivity should depend on the relative stabilities of the transition states TS1 and TS’1. An electron-donating group at the para

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• refluxed in toluene (24 h) partial isomerization was observed (endo/exo = 1:1.6). This behavior can be attributed to the high substitution at one of the alkenes, which might lead to sterically overcrowded transition states required for the rearrangement [27]. Besides, the diastereoisomeric mixture of 3j

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

• points/transition states, as well as experimental details can be found in Supporting Information File 1. CCDC-1833170 (BIFOXSiCl2 (7)), CCDC-1833171 (BIFOXSiCl(OH) (8)), CCDC-1833172 (BIFOXSi(OH)2 (9, dimer)), CCDC-1833173 (BIFOXSi(OH)2 (9, tetramer)), CCDC-1833174 (BIFOXSiCl(OH) 8·acetone) and CCDC

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation

• Łukasz Gułajski,
• Andrzej Tracz,
• Katarzyna Urbaniak,
• Stefan J. Czarnocki,
• Michał Bieniek and
• Tomasz K. Olszewski

Beilstein J. Org. Chem. 2019, 15, 160–166, doi:10.3762/bjoc.15.16

• Marcus postulated a trans-phase hydrogen bonding from water OH groups to H-bond acceptor sites of organic reactants contributing to a stabilisation of organic transition states enables the on-water catalysis [77]. Ben-Amotz et al. demonstrated that the effect of the water OH groups depends either on the

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• the substrate analog inhibitor, (R)-mandelate. In that study all intermediates and transition states were located and characterized. Intriguingly, we identified the tricyclic TCH+ state of the cofactor as an off-cycle intermediate species. It was found to be about 5 kcal/mol lower in energy than the

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

• saturated NHC is considered, the substitution reduces dramatically the barriers of the first two transition states. Then the cycle I→VI is more exothermic with the substituted systems. On the other hand, the unsaturated system does not reduce the energy barriers with the substituted indenylidene moieties

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• )-geometry of the crotylboronate, while the 2,3-anti relationship can be rationalized by invoking Cornforth-like transition states [40][41][42][43]. Eventually, silylation of the homoallylic alcohol 12b afforded the expected compound 13b in 68% overall yield from 5 after purification, compared to 29% using a

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

• imino-carboxylic acid form likely evolves to its iminium-carboxylate form B [50]. This last intermediate involves the existence of two possible transition states for the cyclization of the imidazolidinone core of which one of them is favored by an intramolecular hydrogen bond (Scheme 5). This control is

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• transition states). In the second step we performed solvation energy calculations using the Poisson–Boltzmann self-consistent polarizable continuum method as implemented in Jaguar v.7.9 (Schrodinger, 2013) to represent dichloromethane, using the dielectric constant of 8.93 and the effective radius 2.33 Å

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• M06/def2-TZVP [38][39][40][41]. Frequencies calculations approximated the ZPE correction and entropic contributions to the free energy term as well as confirming all intermediate were true with no imaginary modes and all transition states had the correct critical frequency of decomposition (imaginary

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• enantioselectivity (52 vs 53). Moreover, the more electron-deficient 3,4,5-trifluorophenyl analog 54 was found to be less enantioselective. The authors proposed that the benzylic groups can stabilize the cationic intermediates and/or transition states through cation–π interactions, which play an important role in

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

• intermediate states had only positive frequencies. The transition states have been verified having a single imaginary frequency and connecting the corresponding intermediate structures. The discussions are based on Gibbs free energies obtained within the ideal-gas model using the rigid-rotor harmonic

• reaction routes for the oxazoline formation explored by computations. The schemes indicate the possible stereochemical outcomes. For the definition of the labels of intermediates and transition states see Scheme 3. Free energy profiles for the possible reaction routes. The final energy state (−50.5 kcal

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

• intermediates and transition states. Keywords: catalysis; C–H activation; density functional theory; London dispersion; reaction mechanisms; Introduction For a long time, large and bulky substituents have intuitively been considered to act through unfavorable steric interactions, although London dispersion

• . Selected intermediates and transition states are shown in Figure 2. The computational analysis starts with the catalytically active cobalt(III) acetate complex 4 which is generated in situ from the precatalyst [Cp*CoI2(CO)], AgSbF6, and KOAc. While the iodine ions are captured by Ag+, carbon monoxide

• coordination of acetic acid leads to intermediate 11a. No transition states could be obtained for the following β-elimination and proto-demetalation resulting in product 3a, the cobalt(III) acetate complex 4, and N-phenyl-p-toluenesulfonamide. All attempts starting from different potential transition state

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• of these processes (Scheme 11 and Scheme 12) can be explained by the favored transition states proposed in Scheme 12 based on the fact that the proton transfer constitutes the rate-determining step in the aza-Morita–Baylis–Hillman reaction [58][59][60]. Indeed, in these favored transition states, the

[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

• -diphenyl-1H-pyrazole. The calculated difference in energies of transition states leading to 1,3- and 1,4-diphenyl-1H-pyrazole (4.1 kcal·mol−1 = 17.2 kJ·mol−1) predicts at 140 °C the ratio ≈99:1 which corresponds well with found experimental value >95:5 (see entry 3 in Table 4 [83]). There are only some

• quantum chemical calculations (DFT/B3LYP-6-31G*) [81] steric effects were identified as the main factor influencing the ratio of both regioisomers. These calculations clearly proved the almost apolar character of both possible transition states giving 3- and 4-BPin substituted pyrazoles through bicyclic

• sydnone through the Cu atom in the transition state. This suggestion was supported by Gomez-Bengoa and Harrity et al. [92] who performed thorough quantum calculation of various transition states involving different modes of interaction between 3-phenylsydnone and Cu(I) phenylacetylide (Scheme 16) and

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

• residues that participate in substrate binding or contribute to formation of high-energy intermediates or transition states during the PO-bond cleavage by protein nucleases [8] or ribozymes [9][10]. Based on this data, energetics of various pathways from the reactants to products may be compared by

• , 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

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• ]. As reported in both papers, Mannich bases formed 9a–t were isolated in good yields. Plausible reaction pathways were described and the energetic values of the transition states were calculated. In one of the latest publications with respect to this topic, Priya et al. disclosed the synthesis of a

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• high endo selectivities of 1,2-oxadines 3aa–3ca, 3ab, and 6 would depend on the avoidance of electrostatic repulsion between the nitrogen lone pairs of acylnitroso species with π-electrons of the electron-rich dienes in the exo transition states (exo-lone-pair effect) [36]. Furthermore, the

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• silylacetals) 5 in the aldol reactions (Scheme 2). From this enolate, two transition states A and B can be formed for the aldol reactions. B should be less favored due to the steric (and may be also electronic) repulsion of the aryl and the SF5 groups. Consequently, the syn-products resulting from transition

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• high stereoselectivity of the process could be explained by to the exclusive formation of the pentacoordinated transition states A and B (Scheme 5). Indeed, steric repulsion between the auxiliary and the bulky dimethyl group prevented a Re attack through transition state B, thus forcing the system to

• last few years, further efforts are required to improve limited substrate scopes, yields, and enantioselectivities. In the future, the involvement of other types of ligands will have to be investigated in these reactions with better understanding of the transition states. More generally, only limited

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• in the presence of an aryl or an alkyl group. The number of methylene units between the alkene and the tertiary alcohol function was studied: n = 0, 2, and 3 were suitable for generating thermodynamically favoured 3, 5, and 6-membered cyclic transition states; the reaction failed with n = 1, 4

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• Kuduk et al. [96], remained unsuccessful. The (S)-configuration of the newly generated chiral center of amine 10k was determined by X-ray structure analysis (Figure 7), suggesting two possible transition states for the ligand transfer. Whereas transition state TII requires only one equivalent of AlMe3

• transition states TI and TII for the transfer of the methyl moiety from AlMe3 to the imino moiety. b) X-ray crystal structure analysis of the methyl transfer product 10k. Base-induced rearrangement of propargylamines bearing electron-withdrawing substituents. Base-catalyzed rearrangement of propargylamines

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• a concerted C–N bond formation and C–OMe bond cleavage mediated by a solvent methanol molecule acting as both a proton acceptor from N–H and a proton donor to OMe. All the alternative pathways were associated to transition states lying at significantly higher energy not to be observed experimentally

• participation of one solvent molecule. Most H atoms were omitted for clarity. Optimized geometries for the transition states associated to alternate position of the methanol molecule. Most H atoms were omitted for clarity. Retrosynthesis of the Pro–Pro DKP framework. Coupling with N-hydroxysuccinimide-activated

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• [64]. The stability of the wave functions of all the transition states was checked. An unrestricted wave function was used to calculate the activation energy of the cis/trans isomerization of the (Z,E)-germacranolide. All energies were reported with zero-point energy corrections and all TS geometries