[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

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• nanoreactors is advantageous from kinetic (faster catalytic process) [61] and thermodynamic (lower transition state of reaction) [9] catalysis points of view. Segregation and isolation of catalysts inside nanoreactors guarantee, in most cases, a valuable platform for catalyst recycling [30]. In the following

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• % determined by NMR). Using quantum chemical calculations, we propose approximate transition state models for the stereoselective Michael addition (Figure 2). Geometrical optimizations were performed at HF/6-31G* level and energies were further refined using M06-2X functional with 6-311+G** basis set

• purity of the major diastereomer (er 99:1). With the help of quantum-chemical calculations, we have proposed a transition state model for the Michael addition. Structures of pregabalin and methylpregabalin. Transition state models for the reaction of (R)-6 with dimethyl malonate using catalyst C7 (M06-2X

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

• shown in our earlier investigations. The C–C bond forming step proceeded preferably via a transition state with a syn-arrangement of the SF5 and OTMS groups resulting in the formation of syn-aldol products in case of aldehydes with electron-withdrawing substituents in the para-position or any

• 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

• state A are the major products of the aldol addition reactions. As mentioned above, aldol addition products were not isolated from the reaction of 1 with electron rich p-methyl-, p-methoxy-, and p-ethoxybenzaldehydes. Here, aldol condensation products 4g–i were obtained as single isomers after

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

• undergo a Si attack through transition state A. A related methodology was also applied by Jiménez and Rodriguez to develop the first total synthesis of prepiscibactin, which is an intermediate in the biosynthesis of piscibactin [22]. Indeed, the sequence was based on the diastereoselective SmI2-mediated

• . The stereochemistry of aza-Reformatsky reactions involving N-sulfinyl ketimines is generally explained through a six-membered transition state with the zinc coordinated to the sulfinyl oxygen atom and the enolate carbanion to the imino carbon atom. The other substituents accommodate in order to

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• -membered-ring transition state. Note that the presence of an olefin moiety in the product promised further conversion to other types of CF3-containing molecules. Later, the group of Wang [50] employed cheap copper chloride as the catalyst and a hypervalent iodine(III) reagent 1j as both the oxidant and the

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• C–F amination reactions employing water/isopropanol [3] and triols [4][5] as hydrogen-bond donor activators. Through these studies, the authors suggested that multiple donors (even when using a triol) surround the fluorine atom of the benzyl fluoride, thus stabilising the transition state through

• fluoride ((R)-1, 95%), indicating that a highly associative SN2-like pathway was operating, where the incoming nucleophile must have approached on a coordinate anti to the C–F bond resulting in an inversion of the configuration. These results are in good agreement with the transition state proposed by

Conformational preferences of α-fluoroketones may influence their reactivity

• Graham Pattison

Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284

• that additions to this conformation lead to the most stabilized transition state [17], whilst experimentally, nucleophilic addition of NaBH4 to 2-fluoropropiophenone leads to the anti-diastereoisomer that would be expected by polar Felkin–Anh addition to this conformation [18]. However, around a 90

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• [86]. Importantly, an unsaturated bond has to be present in β-position of the sulphonium center which stabilizes the transition state in the enzymatic transfer from the AdoMet analogue [87]. Engineering of the trimethylguanosine synthase GlaTgs2 from the protozoan Giardia lamblia resulted in a variant

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• ) species 18. During this step, facial selectivity originated partly from hydrogen-bonding interactions between the chiral phosphate and the N–H bond adjacent to the aryl group. Ion pairing interaction in a concerted transition state probably intervened in this phenomenon as well. The final product was then

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• -energy transition state. This can be explained by the stepwise dissociation and subsequent rehydration that are required for ligand displacement (inset, Figure 2B), due to the inherently shielded nature of the buried binding site. In contrast, solvent exposed H-bonds can be more easily substituted by

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• optimized using DFT methods (B3LYP/6-31+g**). In all three cases, the carbon atoms attached to the nitrogen and the N–C(S)–S–C atoms of the dithiocarbamate group are almost in one plane and the torsion angle S=C–S–CF3 is close to zero in the optimized structures. In the transition state corresponding to the

• experimentally and computationally higher than in the other two compounds (4a and 4c). This can be explained by the conformational strain in the five-membered ring in the transition state. In the ground state, the conformation of the pyrrolidine ring is 4T3 with limited steric interactions between adjacent CH2

• hydrogen atoms (Figure 3). On the other hand, a 1E conformation is found in the transition state structure. Hydrogen atoms are close to unfavorable syn-periplanar arrangement in this conformation, which leads to an increased energy demand for the pyrrolidine rotation. Conclusion In conclusion, we have

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• enolate conformation with the allylic hydrogen possessing the same plane for making the steric bias minimum (Int-b) [20][21]. The most important argument for this effect is the stabilization of the forming electron-deficient σ*≠ orbital in the transition state by the electron donation from the neighboring

• orbital interaction would be operative when the electrophile came closer from the re face of the pro-S enolate which suffered from the existence of the sterically demanding iPr group. As a result, the major reaction pathway was considered to follow the transition state TS(pro-R,si) where the si face of

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

• < toluene) have been described to enhance the stability of the transition state, improving the diastereomeric ratio, as well as the reactivity of the nucleophile, resulting in an improved yield [45]. As aldimines have been reported to be rather unreactive electrophiles [53], hard Lewis acids (AlMe3 > AlR3

• addition to sulfinylimines is controlled by the formation of a cyclic, six-membered, chair-like transition state, which is formed by precoordination of the organometallic reagent to aldimine 5 [45]. This cyclic transition state accounts for the preferred re-face attack of the nucleophile at (S)-configured

• 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

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• ] pointing out the importance of such type of compounds in natural biochemical processes [36]. Phosphonic acid mimics the phosphate group, which is omnipresent in nature, but also the tetrahedral transition-state intermediate encountered for instance during the hydratation of carbon dioxide by carbonic

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

• = 2.7 kcal mol−1. The C···N bond distance is slightly shorter in 16b (2.673 Å) than in 16a (2.682 Å). Many attempts to locate a transition state structure for the C–N bond formation starting from either 16a or 16b failed. Even though the geometry optimizations were performed with implicit inclusion of

• . Transition state structures with combined implicit (SMD model) and explicit inclusion of the solvent were thus searched for. The geometry of 16a allowed the creation of a network of stabilizing interactions between an explicit methanol solvent molecule and both the N–H proton and the OMe group (N–H···O

• an explicit methanol molecule the C···N distance in 16a-solv had been reduced to 2.464 Å compared to a value of 2.682 Å in 16a. A transition state structure, TS-16a-solv, corresponding to a concerted C–N bond formation and a C–OMe bond cleavage could be located (Figure 2). Table 3 collects selected

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

• Cope sigmatropic rearrangements. Normally, this reaction proceeds through a transition state with a chair conformation. However, the transformation of schkuhriolide (germacrane) into elemanschkuhriolide (elemane) may occur through a boat transition state due to the final configuration of the

• elemanschkuhriolide, but this transition state is questionable due to its high energy. The possible mechanisms of this transformation were studied in the density functional theory frame. The mechanistic differences between the transformation of (Z,E)-germacranes and (E,E)-germacranes were also studied. We found that

• (Z,E)-germacranolides are significantly more stable than (E,E)-germacranolides and elemanolides. In the specific case of schkuhriolide, even when the boat transition state is not energetically favored, a previous hemiacetalization lowers enough the energetic barrier to allow the formation of a very

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -poor aromatic aldehydes and aromatic ring of the organocatalyst plays a crucial role for excellent yield and selectivity. Apparently the solvent-free system enhances the rigidity of the transition state for more selective reactions under mechanochemical activation. Michael addition Generally strong

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

• sugar during GT-catalysed reactions, GTs are also classified as inverting or retaining (Figure 1). Inverting GTs operate via a SN2 mechanism in a single displacement step where an acid/base residue enhances the nucleophilicity of the acceptor, via an oxocarbenium-like transition state. Unlike inverting

Conformational impact of structural modifications in 2-fluorocyclohexanone

• Francisco A. Martins,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2017, 13, 1781–1787, doi:10.3762/bjoc.13.172

• transition state) or in the ligand assessment to an enzyme binding site. Thus, the replacement of the endocyclic oxygen in 3-fluorodihydro-2H-pyran-4(3H)-one, as well as of the carbonyl oxygen, with other groups, can shift the conformational equilibrium of the resulting molecule towards the equatorial or the