Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• , stands for the stabilization of anionic transition states on π-acidic aromatic surfaces. Anion–π catalysis on carbon allotropes is particularly attractive because high polarizability promises access to really strong anion–π interactions. With these expectations, anion–π catalysis on fullerenes has been

• catalysis; electromicrofluidics; enolate addition; ether cyclizations; fullerenes; Introduction Anion–π catalysis was introduced ten years ago [1]. The idea is to stabilize anionic transition states on electron-deficient, π-acidic aromatic surfaces (Figure 1A). The true beginning is arguably in 2015

• polarizability [9][10][11], the dream scaffolds for induced anion–π interactions are carbon allotropes. Anionic transition states placed on C60 fullerenes 1 will drive the 60 π electrons toward the other side, thus inducing a transient macrodipole that will stabilize the same transition state that induced its

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• investigated the biosynthetic pathways using DFT calculations to validate the above-mentioned aspects. Results and Discussion The detailed structures of the intermediates and transition states were elucidated by computational analysis. Interestingly, we have found an interaction between the secondary

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• site (see transition states 66 and 67, Scheme 17) [45]. In 2020, Fu and co-workers developed a novel aza-Friedel–Crafts reaction between 3-arylindoles 68 and 2-aryl-3H-indol-3-ones 69 activating the C2–H bond of the heteroaromatic ring. Chiral phosphoric acid P12 catalyzed this transformation

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• cation cis-218. On the other hand, when polysubstitution with methoxy groups is present, the cation in 216 is delocalized, inhibiting the production of cyclobutene 217. Thus, radical cyclization according to the Beckwith–Houk model [108][109] via transition states TSI and TSII would take place, leading

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• reactants are confined in the restricted space provided by an enzyme binding pocket, the increase in local concentration, due to the proximity effect, the stabilization of intermediates and transition states cause the acceleration of the reaction. Thus, learning from natural enzymes, novel supramolecular

• capsules [5][6][8][9]. The capsules feature sizeable internal hydrophobic cavities that can accommodate large substrates and even allow bimolecular reactions to take place. In addition, they may ensure catalytic turnover. Transition states and reaction intermediates may also be stabilized in the cavities

• distributions when performed inside the containers compared to the bulk solution. As mentioned above, activation of substrates, stabilization of intermediates and transition states through intermolecular interactions was established as one of the fundamental factors of supramolecular catalysis, and among these

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• reactants, intermediates, transition states, and products were optimized and are illustrated in Figure S7 in Supporting Information File 1. The relative free energy (ΔG, ΔG#) values for all species are presented in Figure 4, the reaction potential energy surface. This figure is a detailed reaction mechanism

• (Scheme 5). The first two stages occur through the TS10, TS15 transition states with Ea values ca. 7.4 and 28.4 kcal·mol−1, respectively. The last stage is a thermodynamically favorable H-shift process with ΔG of −8.9 kcal·mol−1 which is similar to the transformation from IS9 to 10ab. In addition, we

• form an N–H bond leads to 10ab-v3 (Scheme S1, Supporting Information File 1). These processes are carried out through the TS11, TS16, and TS20 transition states with ΔG# values of 4.7, 26.9, and 7.1 kcal·mol−1, respectively. For the reaction pathway starting from 4a’, the first steps lead to

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• ). We studied the inherent chemistry of the reaction leading to HP and IE using gas-phase calculations. This provided the free energy of distinct carbocation intermediates and transition states along the proposed reaction path leading to products in the gas phase. The gas phase is a natural choice as a

• A and A’ is set to zero. Bonds breaking/forming in the transition states are marked by dotted lines. All calculations were performed in the gas phase at the M06-2X/6-31G+(d,p) level of theory. Structures of intermediates C‘ and C. The distance between the double bond and the cation in intermediate C

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• treatment with 1 M HCl produces phthalide 4 through desilylation and following lactonization of F (path d). As can be seen from Scheme 5, the cyclization of D to E is the key step for the formation of compound 6. Therefore, we calculated the intermediates (D and E) and transition states (D–E TS) for this

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• diastereofacial stereoselectivity. Our goal was to identify the nature of transition states associated with two theoretically possible diastereomers and to find out if the experimentally observed diastereomer is more kinetically favorable than the opposite one. The reaction between 3-methyl-3-phenylcyclopropene

• optimization of both transition states TS-4-NI and TS-4'-NI corresponding to pyramidal inversion in cycloadducts 4 and 4' and two pairs of invertomers, we have found that each of the diastereomers 4 and 4' is a mixture of two easily interconverting invertomers (ΔG‡4-exo->4-endo = 1.2 kcal/mol and ΔG‡4-endo->4

• 3-methyl-3-phenylcyclopropene (2j) and corresponding DFT calculations (relative Gibbs free energy change between reagents, transition states and possible products are given in kcal/mol). Plausible mechanism of the 1,3-DC reaction of protonated Ruhemann's purple (1) with 1-chloro-2-phenylcyclopropene

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• the active site of the enzyme. Once bound, substrate activation is carried out by specific amino acid side chains that adorn the inner surface of the cavity by means of a combination of covalent and/or weak intermolecular interactions leading to the stabilization of intermediate species and transition

• states of the reaction with impressive accelerations, substrate, and product selectivities. The development of artificial catalytic systems able to activate substrates and to stabilize intermediate species through weak noncovalent interactions is the scope of supramolecular catalysis [1][2][3][4

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• optimizations of all the intermediates and transition states were carried out with the Minnesota functional M06 [69] with the double-ζ basis set def2SVP [70] and Grimme’s dispersion (GD3) [71]. Harmonic vibrational frequencies were computed to verify the nature of the stationary points. The normal modes of all

• optimization and frequency calculations. Frequency analyses and single-point energies were calculated with the M06 functional [69] with the triple-ζ basis set def2TZVP [70] with the PCM (1,4-dioxane) solvent model [72]. The Gibbs free energies of formation of the reactants, products, and transition states were

• iridium–hydride bond to form hydrometalated intermediates IN2a and IN2b (Figure 1). Two possible transition states, which exhibit a distorted Ir–H–C–C’ four-membered ring geometry, can be located. The concerning free energy barrier about IN1a to IN2a, via 1aTS2a is 8.6 kcal/mol whereas it is 4.9 kcal/mol

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• Information Experimental section, 1H and 13C NMR spectra for all new compounds, as well as selected 2D NMR spectra and crystallographic data for compound 10 are provided. Optimized geometries of the transition states with selected interatomic distances and cartesian coordinates for computed structures are

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• this case, the nitroalkene could not be activated by hydrogen bonding via the (thio)urea moiety, however, it is also probably less sterically hindered (Figure 3a). The DFT calculated transition states support this analysis. The transition state TS-major-re-SR-cat leading to the major stereoisomer of

• sulfur stereogenic center does not play an important role in the Michael addition (Figure 3b). The stereochemical outcome of the Michael addition is dictated mainly by the configuration of the proline unit. The calculated transition states for the Michael addition with both diastereomeric catalysts (S,R

• . Catalyst design principles. DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) structures of catalyst (S,R) and (S,S)-C2, enamine between aldehyde 6c and (S,R)-C2; enamine 6c-(S,R)-C2 and hydrogen-bonded nitroalkene 9. a) Arrangements of reactants in the transition states; b) DFT-calculated (PBEh-3c

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• reported [45], for which a detailed transition state model was developed. In that study, it was determined that the reaction proceeds via several competing low-energy transition states involving both O–H and N–H enolate binding modes, E and Z enolate isomers, and a range of H-bonding and other noncovalent

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• investigated by means of DFT calculations using the reaction between enaminone 6a and phenyl azide. TS1 and TS2 have been proposed as two transition states, which then converted to IN1 and IN2 as two possible isomers. The stable final products were achieved via a cascade reaction including the elimination of

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• based on the operating transition states [37][38]. A cyclic transition state is proposed in the reaction with sodium borohydride. In this transition state, the oxygen of the sulfinyl group interacts with the boron atom, facilitating the release of the hydride, directing the attack to the Si-face of the

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• to give oxocarbenium ion 15, wherefrom two competing transition states, 15a and 15b, can possibly form. In the 6-membered chair-like transition state 15a, there is a 1,3-diaxial interaction between “H” and the substituent R2, while for the other five-membered transition state 15b, there is no such

• transition state 173 instead of the disfavored chair-like transition state 174 to cis,trans-175 as a product (Scheme 42). In contrast, the reaction of anti-170 proceeded, however, through similar boat-like transition states 176 and 177 where the interaction between the methyl substituent and the alkyl group

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• states 21a–k in which both the amide resonance and the resonance of the radical with the carbonyl group are disturbed [83][84]. Reactions via transition states trans-21a–k are energetically favored over the corresponding sterically more hindered cis-oriented transition states cis-21a–k, however, the

• 9m,n with cyclopent-1-en-1-ylmethyl or cyclohex-1-en-1-ylmethyl substituents on nitrogen similarly cyclize via envelope transition states trans-21m,n and cis-21m,n with preferred trans orientation of the olefin unit and the silyloxy-bearing side chain (Scheme 10). Thus, similarly as for 12a–k, two

• products, amides 9g,k with trisubstituted alkene units exclusively lead to isopropenylpyrrolidones 12g,k. A similar reactivity was observed before in thermal radical cyclizations leading to cyclopentane derivatives [74][75]. All γ-silyloxy amides 9a–k cyclize in the 5-exo mode via envelope transition

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• acetylides does not take place. In our case, the transition states TS1 and TS2 have roughly similar energies for phenylacetylene and TS1 is lower in energy for aliphatic alkynes (Scheme 6). Conclusion In conclusion, the rhodium-catalyzed transannulation of N-perfluoroalkyl-1,2,3-triazoles with terminal

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• of CPD with the model nitrostyrene 1h was simulated in silico to predict the reaction pathway, the reaction rate constants, and the activation enthalpies. Density functional theory calculations were conducted for the reactants, products, and transition states using the B3LYP [64][65][66] and M062X

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• VIII compared to the analogue IV (−16.7 vs −0.9 kcal⋅mol−1). The π-donating ability of the nitrogen atom might have a clear stabilizing effect in VIII, while the nitrogen and the cationic allyl system are disconnected in IV. This effect is reflected in the corresponding transition states, with TS3

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• ). The search for the saddle points (starting complexes of both unsaturated compounds 12b and 13, transition states 15A–D and the corresponding Diels–Alder products 14A–D (Figure 4)) showed that the reaction is strongly exergonic and irreversible with an activation free Gibbs energy in the range between

• of other conformations, a lower accuracy of pure functional used, and an incompleteness of the double zeta basis set. The structures of the corresponding transition states 15B, 15C are depicted in Figure 7, and the relative free Gibbs energies of all saddle points for all four stereoisomers are shown

• . Conformations of dihydropyran 12b. The two most stable s-trans (left) and s-cis (right) conformations of dihydropyran 12b. The two most stable transition states endo-trans 15B and exo-cis 15C (hydrogens are omitted for clarity). PES of the Diels–Alder reaction of dihydropyran 12b and maleimide 13. RCEYM with Ru

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• the tert-butyl group but, as a major factor, the corresponding chelated transition states. As all diastereomers 3 can be easily isolated in optical pure form by routine column chromatography, this reaction should be of certain value for biological studies. In this regard, we decided to demonstrate the

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• ). Ideally, to achieve the best selectivity, the β- and the γ-position must be distinctive based on their geometric constraints. We note that the nature of the transition states in this ketone-directed C(sp3)–H fluorination (and the subsequent carbonyl-directed C–H fluorinations) is not well-characterized