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

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• performed. Formation of oxazolidinone 9f There are two possible channels for the cyclization reaction of epoxide 7f with CSI to form oxazolidinone intermediates 10 and 11 as shown in Figure 1. In both transition states it is found that the ring-opening reaction of the epoxide, a nucleophilic attack of N4

• observed oxazolidinone 9f since its precursor intermediate 10 has a remarkably lower activation barrier compared to 11. Methodology All calculations have been carried with the Gaussian 09 program package [58]. Geometry optimizations of all the minima and transition states involved have been performed using

• stationary points to verify whether they are minima (no imaginary frequencies) or transition states (a single imaginary frequency). Thermodynamic calculations have been performed at 25 °C and 1 atm. The same level of intrinsic reaction coordinate (IRC) [62][63] calculations have been performed to check the

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• equiv of NMO, yielding bicyclic derivatives 19 in moderate yields and high diastereoselectivity (de > 95%). The observed diastereoselectivity was rationalized considering two transition states of the PKR, and assuming the CF3 group occupies an axial position due to the steric and electrostatic

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• become apparent [40]. This is because non-equilibrium structures such as transition states that cannot be described by the conventional Lewis model are passed through during reactions. Quantum chemical methods, often in combination with molecular dynamics, can predict the course of a specific reaction

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• ” printed in a Gaussian 09 vibrational frequency calculation. Standard state correction was taken into account. The transition states were optimized with the QST3 or the TS (berny) method. Transition states were identified by having one imaginary frequency in the Hessian matrix, and IRC calculations were

• performed in order to prove that the transition states connect two corresponding minima. General procedure I for the synthesis of compounds 2a,b, 3a,b, 8a,b, and 23a. TFA (0.1 equiv) was added to a solution of 1a–e in DCM (20 mL). After stirring for 24 h at room temperature, an aqueous sodium carbonate

• to the transformations. Relative Gibbs free energy values corresponding to the transition states. Supporting Information Detailed NMR studies (1H NMR, 13C NMR, DeptQ, Dept-135, edHSQC, selective HSQC, HMBC, selective HMBC, NOESY, 1H,1H-COSY, one-dimensional selective NOE, selective TOCSY spectra) of

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• on the reaction path. In this case, the intermediates are likely to be close to, and resemble, transition states. Due to that, their relative energy of formation can be translated to relative reaction kinetic barriers and thus be used, as the first approximation, to predict distributions of the final

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• observed different reactivity of the anhydrides 5–7 towards 1-methyl-3,4-dihydroisoquinoline 19 needs additional explanation. Work in this field based on the theoretical treatment of the possible stabilities of the intermediates and the hypothetic transition states of the steps is in progress. Conclusion

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels–Alder reactions, carried out by calculating the endo/exo transition states, revealed the assistance of non-covalent interactions

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• oxide, while the corresponding 2-phospholene oxides 4a or 7 are the preferred isomers for the unsubstituted or methyl-substituted phospholene oxide derivatives (Table 5, entries 1–3). According to the thermodynamic data without the consideration of the reaction mechanisms and transition states (Table 5

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• shown in Scheme 2. For simplicity, the reaction of benzyl isocyanide (2a) with O-benzyl S-methyl dithiocarbonate (1a) was chosen for the calculations, forming the intermediates Int1–3 via the most probable transition states TS1–3, respectively, which, after hydrolysis, formed the observed product 4a. To

• with Gaussian 09 [36]. The HF/6-31G(d) level of theory in the gas phase was only used to locate the transition state geometries. An intrinsic reaction coordinate (IRC) analysis was conducted for each transition state studied in this work to confirm that the transition states were associated with the

• respective minima. The final IRC structures were further optimized (Figure S14, Supporting Information File 1). The geometries of all reactants, transition states, and intermediates were then fully optimized at the B3LYP/6-311++G(d,p) level of theory in the DMF solvent phase using the polarized continuum

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• -benzyl-protected gluco and galacto derivatives [20][27][30][31]. In addition to exocyclic glycals mimicking putative planar transition states of substrates involved in enzymatic reactions, such as glycosyl transfer, mutase, and epimerization, endo-glycals are also of interest [21][22][32][33][34][35

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• difficult due to their rather nonpolar transition states, which are difficult to be addressed by catalysts [29]. Several stereoselective [3,3]-sigmatropic rearrangements are realized with chiral Brønsted acids [30][31][32][33][34]. Jacobsen reported guanidinium-catalyzed enantioselective Claisen

• activate the enolates or the corresponding silyl ketene acetals or stabilize the corresponding transition states. In addition, chiral organocatalysts could induce diastereo- as well as enantioselectivity. Therefore, we examined the Ireland–Claisen rearrangement of ester 1c in the presence of a range of

• rearrangements proceed via isopolar transition states and, therefore solvent effects are rather small. For this reason and due to the complete lack of enantioselectivity, at this stage, we did not investigate other solvents with the catalysts collected in Figure 1. In order to gain further insight into the

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• derivatives are predicted to occur through a transition state in which the N atom next to the benzene ring linearizes in an inversion mechanism (see B-type transition states in Figure 2 for 4pzH-F2 and 4pzMe-F2, and Figure S1 in Supporting Information File 1 for the rest of di-ortho-substituted photoswitches

• the possible conformers both in the Z- and E-forms were fully optimized by using the hybrid exchange-correlation PBE0 functional [37] including the Grimme’s dispersion correction in its latest version (D3) [38]. The split-valence Pople’s basis set 6-31G** was used throughout [39]. Transition states

• were optimized by using the Berny algorithm at the same level of theory [40]. Theoretical calculations were carried out in the gas phase. Theoretical kinetic studies were carried out at the PBE0-D3/6-31G** level of theory by considering all possible transition states and minimum-energy conformers for