An aniline dication-like transition state in the Bamberger rearrangement

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 1073–1082, doi:10.3762/bjoc.9.119

• –N(OH)H + H3O+(H2O)n (n = 4 and 14) was examined. However, the rate-determining transition states involving proton transfers were calculated to have much larger activation energies than the experimental one. Second, a reaction of the diprotonated system, Ph–N(OH)H + (H3O+)2(H2O)13, was traced. An

• activation energy similar to the experimental one was obtained. A new mechanism of the rearrangement including the aniline dication-like transition state was proposed. Keywords: Bamberger rearrangement; DFT calculations; N-phenylhydroxylamine; proton transfer; reactive intermediates; transition states

• the Cl-containing model, 6-31(+)G(d) was used where the diffuse sp function is only the chlorine atom. Transition states (TSs) were sought first by partial optimizations at bond-interchange regions. Second, by the use of Hessian matrices, TS geometries were optimized. They were characterized by

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• blocks in the synthesis of the nucleotide analogues with enhanced affinity for receptors and better charge correlation with transition states for selected kinases. Two synthetically useful approaches to the parent trisphosphonic acid HC(PO3H2)3 have been developed. One of the procedures is based on the

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• ). Finally, the protonolysis reaction of the carbon–gold bond by TfOH renders the final products 3M and 4M regenerating the catalyst. This step occurs through the transition states TS2-A and TS2-B, respectively, in an exergonic transformation (ΔGR,298 = −4.5 and −3.0 kcal/mol from INT3-A and INT3-B

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• transition states in chemical reactions, especially for predictive catalysis. It is particularly suitable for stereoselectivity calculations where there is a need to virtually screen large ligand libraries [1]. Another example are the so-called QM/MM methods [2], where part of the structure is treated with

• function of SS in methanol for series C. Optimized geometries, relative energies, and imaginary frequencies for the transition states and the σ-complex (middle structure) formed in the reaction between ammonia and 4. The top and bottom rows show the results from optimizations at the B3LYP/6-31+G(d,p) and

Ring opening of 2-aza-3-borabicyclo[2.2.0]hex-5-ene, the Dewar form of 1,2-dihydro-1,2-azaborine: stepwise versus concerted mechanisms

• Holger F. Bettinger and
• Otto Hauler

Beilstein J. Org. Chem. 2013, 9, 761–766, doi:10.3762/bjoc.9.86

• have performed explorative computations using the CASSCF(6,6)/6-31G* method and could locate transition states for the conrotatory (TS1; nimag = 1, i556 cm−1) and disrotatory (TS2; nimag = 1, i628 cm−1) ring opening of 3. Computation of the intrinsic reaction coordinates confirms that both TS1 and TS2

• connect the Dewar form 3 to 1,2-dihydro-1,2-azaborine. These transition states are similar in geometry to those described earlier for the all-carbon system (see Figure 1 and Figure 2) [14]. The C1–C4 distance is shorter in TS1 (2.247 Å) than it is in TS2 (2.313 Å). The BN unit is a bystander in these two

• mechanisms as it is not involved in the ring-opening process. The energies of these transition states were refined with multireference perturbation theory (MRMP2). In agreement with the results obtained for the all-carbon system [14], the barrier for the orbital-symmetry-allowed conrotatory ring opening is

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• two quaternary carbons (C1 and 5) and the C12-stereocenter. The selective formation of 8 out of eight possible isomers is rationalized in Scheme 4. The endo-type transition states would be favored over their exo-type counterparts, and acrolein would approach from the bottom face of 7 to avoid steric

• interactions with the axially oriented C2- and C4-hydrogen atoms on the top face [27]. These considerations eliminate six out of the eight stereoisomeric transition states, and leave only TS-A and TS-B, which in fact correspond to the generated adducts 8 and 20, respectively. TS-A would be preferred over TS-B

Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

• Martina Bonsignore,
• Maurizio Benaglia,
• Laura Raimondi,
• Manuel Orlandi and
• Giuseppe Celentano

Beilstein J. Org. Chem. 2013, 9, 633–640, doi:10.3762/bjoc.9.71

• , and the two lowest energy transition states (TS) leading to the formation of R and S amine were located. In order to simplify the problem, we adopted a stepwise procedure for the location of the TS structures. First of all, a conformational analysis with Monte Carlo techniques was performed with MMFF

• this work. Catalysts synthesized and studied in this work. Calculated transition states for catalyst 6. Stereoselective reduction of ketones. Enantioselective reduction with catalyst 1.a Enantioselective reduction of the N-phenyl imine of acetophenone.a Enantioselective reduction of differently

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• and Discussion The various transition states, intermediates and products initially considered for the three reaction paths A, B, and C are depicted in Scheme 3. It turned out that not all of the structures shown in Scheme 3 could actually be located as stationary points on the potential-energy surface

• . On the other hand, some other stable as well as highly reactive intermediates and/or transition states were obtained (see below). Generally, in nucleophilic addition reactions to carbonyl compounds in aqueous solution, water not only acts as a solvent but frequently actively participates in the

• transition states, intermediates and products shown in Scheme 3, hydration by six water molecules is implied. Relative Gibbs free energies with respect to the separated reactants 1·(H2O)2 + [OH(H2O)4]– including bulk aqueous solvation energies (SMD solvation model [21]) obtained by various computational

Complete σ* intramolecular aromatic hydroxylation mechanism through O₂ activation by a Schiff base macrocyclic dicopper(I) complex

• Albert Poater and
• Miquel Solà

Beilstein J. Org. Chem. 2013, 9, 585–593, doi:10.3762/bjoc.9.63

• B3LYP/6-31G(d) level were used to perform single-point energy calculations with a larger basis set, the 6-311G(d,p) basis set [63], and the same functional (B3LYP/6-311G(d,p)//B3LYP/6-31G(d)). Intrinsic reaction pathways were calculated to confirm that the located transition states connected the

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• dispersion correction method (ωB97XD [29]) were applied to the rate-determining step of the propene reaction TS1(Me). The basis sets employed were 6-31G(d) and 6-311+G(d,p). Transition states (TSs) were sought first by partial optimizations at bond interchange regions. Second, by the use of Hessian matrices

• Information File 1). These were found to be similar to diol(Me), ene-ol(Me), ether(Me) and dioxane(Me) in Figure S1, respectively. Thus, those TSs were confirmed to be in the reaction channel. Figure 2 exhibits geometry-dependent energy changes for the transition states depicted in Figure 1 and Figure S1. TS1

• -diol or to the carbocation X. While the intervention is suggested to depend on the concentration of water, in aqueous media the cation is unlikely owing to the high nucleophilicity of the large water cluster. Geometries of the precursor and the transition states (TSs) of the Prins reaction of propene

Electron and hydrogen self-exchange of free radicals of sterically hindered tertiary aliphatic amines investigated by photo-CIDNP

• Martin Goez,
• Isabell Frisch and
• Ingo Sartorius

Beilstein J. Org. Chem. 2013, 9, 437–446, doi:10.3762/bjoc.9.46

• reversibility of that deprotonation can be discounted. Sterically, that deprotonation is much more demanding than the hydrogen self-exchange, as Newman projections of the expected transition states show. With both reactions, there are four gauche interactions between methyl and a large group (iPr or N(iPr)2

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• computational calculations using the hybrid functional of Becke [46] and Lee, Yang and Parr [47]. Geometry optimizations of the reactants, the transition states and the cycloadducts were performed at the B3LYP/6-31+G* level. Stationary points were analysed by frequency calculations at the same level to confirm

Presence or absence of a novel charge-transfer complex in the base-catalyzed hydrolysis of N-ethylbenzamide or ethyl benzoate

• Shinichi Yamabe,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 185–196, doi:10.3762/bjoc.9.22

• minimal model of TS1 was proposed and was found to be insensitive to n. Keywords: basic hydrolyses; DFT calculations; ethyl benzoate; N-ethylbenzamide; reactive intermediates; transition states; Introduction Basic hydrolyses of esters and amides have been extensively studied experimentally [1]. Use of

• adopted method or not in relation to the former part of point 3. Transition states (TSs) were sought first by partial optimizations at bond-interchange regions. Second, by the use of Hessian matrices, TS geometries were optimized. They were characterized by vibrational analyses, which checked whether the

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• enantioselectivity, DFT calculations on the enantio-determining transition states were performed by employing the nonempirical TPSS-functional and BP86. Two possible pathways were found computationally (pathway A, B, Scheme 4). The first essential step in the catalytic process is the formation of the imine

• . The addition of 4-hydroxycoumarin to the activated Michael system 12 could now occur along two slightly different mechanistic pathways (A, B, Scheme 4) including the enantio-determining transition states corresponding to TS-13 or TS-14. Both pathways require the formation of a carbon–carbon bond and

• )-enantiomer of 17 should be generated in majority. The experimentally favored enantiomer is indeed (R)-configured with 83% ee (Table 2, entry 7). This value is in good agreement with an energetic differentiation of the enantio-determining transition states of 2.3 kcal/mol although no solvent dependent effects

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• involving polar intermediates and/or transition states has been investigated on a broad scale for the first time. The reactions studied include lithiation, reaction of the thus formed organolithium salts with various electrophiles (among others, allyl bromide, DMF and acetone), oxidation to cyclopentenones

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• . Extensive DFT calculations, including solvent effects and dispersion corrections, as well as ab initio calculations provide a plausible description of the reaction mechanism. Keywords: bifunctional organocatalyst; DFT calculations; guanidine-thiourea; Michael addition; organocatalysis; transition states

• and H-transfer. The thermodynamics of both routes are comparable at all levels. Once ternary complex Init10 is formed, there are few C–C bond-forming pathways. Based on the extensive conformational search, we were able to find eleven competing transition states (Figure 3 and Figure 4), six of which

• ), at all levels employed, compared to the corresponding transition states that lead to the R product. The activation barriers vary between +7.3 kcal·mol−1 (+7.5 kcal·mol−1 DFT-PCM, TS8 S) and +14.1 kcal·mol−1 (+14.5 kcal·mol−1 DFT-PCM, TS7 R). DFT-D and MP2/6–311++G(d,p)//6–31G(d) results support the

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• reactions [4][73][74][75][76][77][78][79][80]. Quantification of the nucleophilic reactivities of the enamines 32a–e in acetonitrile (20 °C) [83]; a definition of the Dunitz pyramidalization Δ is given in [84]. Proposed transition states for the stereogenic step in proline-catalyzed reactions. Kinetic

Toward unidirectional switches: 2-(2-Hydroxyphenyl)pyridine and 2-(2-methoxyphenyl)pyridine derivatives as pH-triggered pivots

• Christina Tepper and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2012, 8, 977–985, doi:10.3762/bjoc.8.110

• for use as a unidirectional pivot. If the phenolate 1 is protonated (grey arrow in Figure 1a), the most-stable conformation of the phenol 2 can be reached either by a clockwise or a counterclockwise rotation around the C–C single bond (black arrows in Figure 1a). As the transition states for both

• kJ·mol–1. According to the Boltzmann distribution between the two transition states, the rotation is almost completely (>99.9999%) unidirectional at 298 K. It must be emphasized that the rotation caused by the protonation of 5 and 7 is unidirectional only with respect to a single molecule. In equilibrium

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• and ρ < 1 factors in that with BS. To verify whether the measured enantioselectivity is determined by the relative stability of the starting diastereomeric complexes or by the transition states involved in the reaction path, the collision-induced dissociation spectra of the [V∙H∙tyrOMe]+ and [V∙H∙amph

Thermodynamic and kinetic stabilization of divanadate in the monovanadate/divanadate equilibrium using a Zn-cyclene derivative: Towards a simple ATP synthase model

• Hanno Sell,
• Anika Gehl,
• Frank D. Sönnichsen and
• Rainer Herges

Beilstein J. Org. Chem. 2012, 8, 81–89, doi:10.3762/bjoc.8.8

• presence of metal cations such as Zn2+, Mg2+ and Mn2+ in the active site [9]. It is generally assumed that the coordination of the metal cations to the phosphate oxygen atoms reduces the Coulomb repulsion in the transition states or in the intermediates, thus, lowering the activation barrier [10]. In

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• observed regioselectivity over the course of the reaction. If the rate-determining step of the reaction is endergonic, then differences in productlike transition states will account for the observed selectivity according to Hammond’s postulate [44]. For the reaction path to the most constrained macrocylic

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• gave none of the required product. An aldol type reaction with benzaldehyde (Table 1, entry 9) afforded alcohol 6i in good yield, with complete diastereoselectivity at C-6, but no selectivity at the alcohol stereocenter (1:1). Examination of the two possible Zimmerman–Traxler type transition states for

• equatorial position, as there is now a 1,2-gauche interaction with the bulky di-methoxyaryl group adjacent to it. We consider that neither of these transition states is lower in energy, which would be consistent with the lack of diastereoselectivity. Finally, the addition of (R)-propylene oxide as the

Alkene selenenylation: A comprehensive analysis of relative reactivities, stereochemistry and asymmetric induction, and their comparisons with sulfenylation

• Vadim A. Soloshonok and
• Donna J. Nelson

Beilstein J. Org. Chem. 2011, 7, 744–758, doi:10.3762/bjoc.7.85

• intermediates usually of rate-determining transition states, exhibit characteristic patterns in their plots of log krel versus ionization energy (IE) or highest occupied molecular orbital (HOMO) energy [72][73][74][75][76]. These patterns were shown to be particularly useful to reveal the steric forces within

• , and electronic characteristics of, the rate determining transition states. Thus, plotting log krel values against IEs or HOMO energies of alkenes allows a comparison of the significance of steric and electronic effects in the rate-determining step of the reaction. In particular, additions to alkenes

• , that proceed via 3-membered intermediates (or transition states), display plots with one trend line if the reaction rate is predominantly dependent upon electronic effects [72][73][74][75][76], and multiple trend lines if both steric and electronic effects are important [72][73][77][78]. In this work

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• + 2] cyclization lying only 4.4 kcal/mol above the starting complex. Further calculations on the barrier for transition states were also consistent with the rapid conversion that was observed in the experiments. Overall, the large energetic preference of the intermediates and transition states for the