Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• displacement, both via two distinct oxocarbenium-like transition states [16]. In all three mechanisms, the nucleophilic attack of the acceptor is enhanced by the deprotonation – either by an acid/base residue, like in inverting GT and two-step displacement retaining GT, or the phosphate donor (in an SNi-like

• retention of configuration (Figure 5) as first described by Koshland [53]. However, in the case of GHs, the mechanism generally implies the intervention of two amino acid side chains, typically glutamate or aspartate, and goes through oxocarbenium ion-like transition states. Inverting GHs operate via a

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• DFT calculations. Geometrical parameters of reactants, transition states (TS), and products were fully optimized in dichloromethane with the M06 method using the GEN basis set combination 6-31+G(d) and LANL2DZ in the Gaussian 09 software package [33]. Computational details are given in Supporting

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• held far from equilibrium through the energy-fuelled supply of reactive units. Kinetic control. In many chemical reactions leading to different products, the final composition is determined by the height of the kinetic barriers corresponding to transition states (TS‡1 and TS‡2) rather than by the

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• hydrolysis transition states as well as having many other interesting properties. They are found in nature as pyrrolidines, piperidines, indolizidines, pyrrolizidines or nortropane alkaloids with a variety of ring substituents, typically hydroxy groups, carboxylic acids and amides [1]. The ability of

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• (12E →12F→ TS3 → 9) with a value of 12.7 kcal/mol. These results are in accordance with the observed formation of the twelve-membered ring of dimer 9 formed in the reaction of 8 [13]. The order of the free energies of the transition states (TS3 < TS4 ≈ TS5) reflects the steric requirement to reach the

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• formed in a single concerted step, via five-membered transition states TS 2, 4, and 5 (Table 9) and the additions are in all cases exothermic. The reactions with dimethyl phosphite are more favorable than those with diphenylphosphine oxide. It can also be seen that the additions to N-benzylideneaniline

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• mimic enzymatic reactions through the electrostatic substrate activation or stabilization of charged transition states or reaction intermediates. At the same time, recent studies highlight the importance of other types of non-covalent interactions such as the activation through the formation of C–H···A

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• Thrular’s functional M06 [44] and 6-31+G(d,p) basis set. A simplified model, able to correctly mimic the system, was considered and the reaction between dipolarophile 8 (Z and E) and nitrone 4 (Scheme 3) was studied. The reaction pathway was considered and the transition states leading to the (R,R)-9 or (R

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• centers have been proposed by Bacon [68] and were elaborated by Litvak [69] who proposed SET within the 4-membered transition state. It is noteworthy that modern DFT calculations [63] also produce cyclic transition states. Conclusion In conclusion, we observe direct arylation reactions (C–X/C–H; X

• = halogen) catalyzed by a Cu(I) center stabilized by an ambiphilic ligand. The activation of stable sp2 C–H bonds in benzene and naphthalene occurs as a result of the catalysis. We favor a mechanism involving 4-membered cyclic transition states for metalation–deprotonation followed by concerted oxidative

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• the transition state corresponding to the concerted mechanism, e.g., via TS 1a_1−3a (Scheme 4). Interestingly, isoxazolines 9 and 10 with cis orientation of the Az and NMe2 groups, were found to be the products of transition states 1a_3−9 and 1a_3−10, respectively, both based on 1a_3 geometry of

• enamine 1a, whereas transition states based on 1a_1 geometry of the enamine lead to isoxazolines 3a and 8 with trans orientation of the Az and NMe2 groups (Scheme 4). Thus, one could conclude, that the configuration around the double bond of the enamine controls the stereoconfiguration of the isoxazoline

• isoxazolines [46]. It is remarked, that transition states 1a_1−3a and 1a_3−9 have longer lengths of the forming bonds compared to those of transition states 1a_1−8 and 1a_3–10, which indicates an easier attainability of the formers. Calculations of the thermodynamic parameters suggest that transition state

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• conformers with M and P helicity (conformer A and B, respectively). The relative energy (kJ/mol) is plotted as the function of the ωC12−C13−C3’−C9 torsional angle. TS1 and TS2 denote the two transition states for the inversion of the helicity. Transition states for the inversion of the helicity [TS1 (ωC12

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• Pioneering computational studies on the mechanism of the intermolecular nitroso hetero-Diels–Alder reaction by Houk [79][80] demonstrated that the reaction proceeds in a concerted fashion through an asynchronous transition state. In the two calculated transition states (endo and exo), the ratio of the

• lower the chemoselectivity. Moreover, DFT calculations of this type of reaction confirmed the preference for endo transition states. These calculations showed that the acylnitroso species are superreactive, and the activation energies are lower than the isomerization barriers between some cis and trans

• transition states, where the distal isomer is unfavored due to steric repulsions between the side chain and the acetonide group. Chiral dienes: The use of chiral cyclic and acyclic dienes for both acyl and arylnitroso dienophiles is well reported in the literature. This is in part due to the extensive use of

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• [222]. The tetramolecular transition states TS1 and TS2 are considered to be the two key steps determining the course of the oxidation: the nucleophilic addition of a peroxy acid molecule to ketone (TS1) and the migration of R and cleavage of O–O bond (TS2). Thus, electrophilic substrates favor TS1 and

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• the vacant p-orbital on the carbene carbon affects the electronic structure of the transition states. The halocarboethoxy carbenes are also more stabilized than the carbene generated from EDA. The energy gain from the transition state to the free carbene is 18–20 kcal/mol for X = F, Cl and Br, but

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• was any enthalpic barrier to elimination of the protonated methoxy group, geometric scans for potential transition-states were made using Density Functional Theory calculations, by incrementally increasing and fixing the C(2)─OMe bond length for rotamers 16a–c after protonation, and allowing all other

Ring-whizzing in polyene-PtL₂ complexes revisited

• Oluwakemi A. Oloba-Whenu,
• Thomas A. Albright and
• Chirine Soubra-Ghaoui

Beilstein J. Org. Chem. 2016, 12, 1410–1420, doi:10.3762/bjoc.12.135

• –NiL2. The experimental barriers range ≈5–6 kcal/mol [69][70][74]. The aforementioned calculations [45][75] yield barriers of 4.2–9.5 kcal/mol in reasonable agreement with the experiment. The structures of these transition states resemble η4 species with the geometry akin to 52 in Figure 15. This is not

• which is in line with the calculations by others. Therefore, the discrepancy must lie in the difference between Pt and Ni. There is also a difference in the metrical details of these transition states. For the Ni examples the Ni–C(1) and Ni–C(4) distances are ≈0.3 Å longer than the Ni–C(2) and Ni–(3

• cyclobutadiene. The computed ground state (15) and transition state (16) for cyclobutadiene–Pt(dpe) on the right. The ground and transition state for ring whizzing in F6C6–Pt(dpe), 17 and 20, respectively. The dominant bonding interaction for two possible transition states, 18 and 19 along with the HOMO, 21 and

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• not shown). The absolute configuration of cyclopentanes 3’ and 3’’ were determined based on the derivatives 7h’ and 7h’’ of 3h (Scheme 2) [95]. We proposed two possible transition states (TS) 8a’ and 8a” to rationalize the observed configurations (Scheme 3). The trans-C=C double bond in iminium ion 4

• product 3a in 83% yield as a colorless oil. Catalytic regio- and enantioselective [3 + 2] annulation reactions of 2-vinylcyclopropanes with enals. Single X-ray crystal structures of 7h’ and 7h’’. The proposed transition states. Screening of lewis acids.a The optimization of reaction conditions.a Scope of

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• between TDTS and TDI is the maximum energy span between a given intermediate and all following transition states of the cycle and can be understood as the overall Gibbs free energy of activation of the whole catalytic cycle [65]. This procedure can be translated to competing reaction paths. For pathways

• 1a and 1b (Scheme 3), the rate-determining intermediate (RDI) is W(CO)5(Z-2) and the rate-determining transition states (RDTS’s) are TS(W(CO)5(E-2) → W(CO)5…E-3) (pathway 1a) and TS(W(CO)5(Z-2) → W(CO)5(Z-3) (pathway 1b) giving the overall Gibbs free energies of activation ΔG‡total = 287 kJ mol−1 and

• carbenes E-2/Z-2 from W(CO)5(E-2)/W(CO)5(Z-2) is calculated endergonic (ΔG = 141 kJ mol−1 and ΔG = 167 kJ mol−1, respectively, Scheme 3). Transition states for the carbene dissociation could not be identified. Hence, this initial dissociative step is probably not the one with the lowest energy. Nonetheless

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• core potential (ECP) on hexa-coordinate indium [51] as implemented in Gaussian 09 owing to the predicted good results in our earlier work [30]. The remaining coordination sites of indium were occupied by two THF molecules. The minima and transition states of the calculated structures were verified by

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• developed by means of DFT calculations on potential transition states. Keywords: amino acids; camphorsulfonylimine; DFT calculations; NMR characterization; Strecker degradation; Introduction Among the many derivatives of natural camphor, oxoimine 1 (Figure 1) shows an especially versatile chemistry. The C

• (Figure 8) as the products [34][35]. We could indeed identify transition states for these reactions. Figure 8 (top) shows the reaction sequence and Figure 9 shows the TS and the change in salient atom distances along the path following the intrinsic reaction coordinate (IRC). A movie is available as

• is an obvious candidate as catalyst. Indeed, water inclusion in reaction paths with high-lying transition states is often observed in water as solvent, as in biochemical reactions, and was demonstrated for, e.g., the analytical detection of sulfenic acids with dimedone [36]. In these systems water

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• reaction pathway based on previously reported transition states (Figure 6). The catalyst ent-4 would activate and fix the electrophile through several hydrogen-bonding interactions with the NH groups of the thiourea. Simultaneously, the hydroxy group would be involved in the activation of the nucleophile

• external Brønsted acid. Proposed transition state TS7 for the Friedel–Crafts reaction of indole and α,β-unsaturated acyl phosphonates catalyzed by ent-4. Possible transition states TS8 and TS9 in the asymmetric addition of indoles 2 to the β,γ-unsaturated α-ketoesters 26 catalyzed by ent-4. Transition

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• trajectories initiated from minima and transition states have both been carried out on carbocations [25] and examples of each are described below. While many different quantum chemical methods can be used to carry out trajectory calculations, standard density functional theory (DFT) approaches are most

• structures in the vicinity of transition states, tend to have short lifetimes, on the order of the period of a single-bond stretching vibration. • These lifetimes can be increased via noncovalent interactions with electron-rich groups. Abietadiene – navigating past forks in the road Pathways to abietadiene

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• substituted with the two carbon atoms arm where only compound myo-5 could be obtained. Indeed with the chain being longer, the formation of byproducts originating from cyclization and migration, favored by the proximity of the inositol ring and preferential transition states, was avoided. The synthetic routes

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• into the isomeric spirotricycle 12a. The computed energy barriers for these processes are relatively small, 13.9 and 17.0 kcal·mol−1 respectively. Again the differences in the extent of the electronic conjugation in these electrocyclization transition states can give account of the relative stabilities

• characteristics of the respective transition states. The calculations have also shown that the tandem conversions of the starting fulvenes into benz[f]indenes are exergonics, the 9-substituted regioisomer being the thermodynamically-controlled major product, in accordance with the experimental results. Optimized

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• Diels–Alder products (Table 1). Single-point energies of the transition states suggested that pathway a was preferred over b (difference of ca. 10–20 kJ/mol). This was further supported by comparison of Gibbs free energy values. Boltzmann distribution was used to calculate theoretical endo/exo

• selectivity of 16a (98:2) from the differences of Gibbs energy of the transition states. Geometries of the four transition states are depicted in Figure 1. The less abundant transition states (TS-endo-16b and TS-exo-16b) were asynchronous with the differences of bond lengths of 0.662 and 0.556 Å, respectively

• )acetic acid, which in aqueous solution exists in equilibrium with its enol form. Further experiments are underway to find out whether aerobic microbial degradation of SF5-substituted aromatic compounds follows the same pathway as our chemical oxidation method. Optimized geometries of transition states of