Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• (PCM) solvent (Figure 4). The reaction initially started with the addition of benzyl azide to one of the internal alkynes of 5. Although the benzyl group is situated on the interior side of DBA, a more energetically unstable transition state (in-ts) is generated. However, the resulting monoadduct (in

• the experimental observation that no monotriazoles were obtained. During the second azide addition, the orientation of benzyl azide is once more controlled. The benzyl group positioned on the inner side results in a thermodynamically less stable transition state (in-in-ts) compared to that on the

• was taken into account by the polarizable continuum model using the integral equation formalism (IEFPCM) [25] for DFT calculations. The optimized molecular structures were verified by vibrational analysis; equilibrium structures did not have imaginary frequencies and transition-state structures had

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• indazole and the deprotonated indazole was only −0.2 kcal/mol (Figure 11). Again, no preorganized intermediates were found. The NCIs were consistent with the parent system. The hydrogen bond between the H on the electrophilic methyl group and an ester oxygen was found in the transition state leading to the

• N1 product, was conserved (18-N1-OMe, Figure 11), in a total of 4 NCIs. The only relevant NCIs in 18-N2-OMe were between an aryl hydrogen, N1 and an ester oxygen, the result of which is ΔΔG‡ = 2.0 kcal/mol favoring the N1 transition state 18-N1-OMe among the NCIs found. To further probe whether the

• stabilization, nucleophilicity would dictate regioselectivity outcomes. This also implies that the favorable NCIs and chelation are stronger driving forces towards transition-state energy partitioning than nucleophilicity alone. These results suggest chelation is a highly plausible driving force for

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• , and transition-state structures were optimized by density functional theory (DFT) calculations employing the software Gaussian 16 [34]. Although the B3LYP functional could be suitable for these calculations, e.g., for tracing reaction pathways, nitrations, halogenations, or FC acylations in solution

• ) must exhibit only positive harmonic frequencies, whereas each energy maximum (transition state) exhibited only one negative frequency. From these last calculations, zero-point energy, thermal, and entropy corrections were obtained, which were added to the electronic energy to express the calculated

• rise to the chlorinating species I-2–Cl in equilibrium with I-3–Cl. At this point, 2-naphthol reacts, leading to the formation of the ion pair I-4–Cl via chlorine atom transfer, which then yields the adduct I-5–Cl trough transition state TS2–Cl. Then, the release of the second equivalent of the TFAO

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• intramolecular fluorine-atom-transfer (FAT) from an N-fluorinated amide to a pendant carbon-based radical formed from an iron catalyst (Figure 15) [55][56]. This concept of fluorine transfer through a 6-membered transition state was shown to work efficiently from primary, as well as secondary, benzylic radicals

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• of a hydride ion from a tetracoordinated intermediate (B), which is formed upon hydroxide addition to the aldehyde (A). The primary pathway of the reaction entails the rate-determining step of hydride ion transfer via either a linear or bent transition state (C) to a second molecule of aldehyde

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• barrier through the chair–chair transition state of 28.1 kcal mol−1 and an overall ΔG from 2 to 10a/10b, which have the same predicted energy, of −2.0 kcal mol−1 (Figure 3B). The relative free energy barrier through the chair–boat transition state was calculated to be 36.9 kcal mol−1, but would require a

• , Supporting Information File 1). The lowest transition state for a Cope rearrangement, a chair–chair structure at 29.3 kcal mol−1, originates from a DD (down–down orientations of the methyl groups on the 10-membered ring) conformer that is 3.2 kcal mol−1 higher in free energy than the most dominant conformer

• previously reported [10]. A biosynthetically related analog is similarly proposed to undergo oxy-Cope rearrangement to yield 13a/13b. (B) Results of DFT calculations indicate that the Cope rearrangement of 2 is more favorable via a chair–chair transition state than a chair–boat transition state. (C) Results

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• study indicates that the retro-IMDAF reaction does not occur under the reaction conditions developed. As seen in Figure 4b, the different sigma bond lengths formed in the exo transition state (calculations which were performed in Gaussian 16 Rev B.01 (Gaussian, Inc., Wallingford, CT, USA)) [135

• ] indicate that the IMDAF reaction proceeds through an asynchronous process (the same is true for the endo transition state). Accordingly, the length of the σ bond formed near the amide functional group was calculated to be 2.012 Å, while the length of the bond formed on the far side was calculated to be

• 2.160 Å. These bond lengths support path I, which is a more valid pathway in the reaction mechanism. As can be seen in Figure 4, the energies of both the exo transition state and the exo product are lower than those of the endo, which also supports the experimental results. Conclusion Vegetable oils

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• the transition state was ascribed to the donor–acceptor interactions between the HOMO of the silylene and the LUMO of ethylene, and vice versa [42]. For 2a, the LUMO is largely distributed at the e' bonds, followed by the cis-2 and trans-3 bonds (Figure 8). These results suggest that the formation of

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• cytosine deamination involves a nucleophilic attack at the C4 position by a Zn2+-activated water molecule [40][41][42], it was proposed to employ transition state analogues and mimetics of the tetrahedral intermediate formed as inhibitors of these enzymes [43][44][45][46][47]. More than 30 compounds have

Novel route to enhance the thermo-optical performance of bicyclic diene photoswitches for solar thermal batteries

• Akanksha Ashok Sangolkar,
• Rama Krishna Kadiyam and
• Ravinder Pawar

Beilstein J. Org. Chem. 2024, 20, 1053–1068, doi:10.3762/bjoc.20.93

• -transition state bifurcation (PTSB) of the PES [39][40]. Consequently, the reaction tends to produce two different products from a single TS. Thus, the reaction resembles a peculiar ambimodal reaction that can produce multiple products from a single TS structure [41]. Owing to the formation of two singlet

• photoswitching cycle. The dissociation of two newly formed σ-bonds during the thermal back isomerization proceeds in a highly asynchronous mechanism. Initially, only one of the two newly formed σ-bonds is dissociated leading to the formation of singlet biradicals in the transition state (TS) structure. Therefore

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• upward, therefore creating an asymmetric center with absolute configuration (R), in accordance with experimental results. A rationalization for the transition state that would lead to the observed outcome is depicted in Figure 2. Conclusion The palladium-catalyzed Heck–Matsuda desymmetrization of N

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• compounds show a very similar absorption band, indicating that the first transition state (S0 → S1) does not seem to be affected by the substitution pattern. Furthermore, all compounds show broadened absorption bands and no major differences in the first absorption band were observed. The greatest

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• synthetic intermediate of 2 to spiroviolene. By taking advantage of the DFT transition state analysis of the hydroboration reaction of a key intermediate, as well as NOE correlation analysis of the resultant product, Snyder and co-workers have reassigned the right structure of spiroviolene to 1. However

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• work, which suggests a stepwise migration of oxygen from C5 to C4, followed by addition of the halogen nucleophile. Furthermore, if the halogen was involved in the transition state via the σ* orbital (avoiding intermediate 27), the opposite configuration would result at C2 in the products. The single

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• effective transition state includes the electrophile positioned in the equatorial site (strongly coordinated) and the nucleophile in the perpendicular site (weakly coordinated) [19]. The most favourable orientation of aldehyde should be out of the ligand’s molecular parts, thus forming E-configuration at

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• mechanism to a <1st-order dependence on catalyst, which could indicate a competing alcohol or H-bonding driven mechanism. In CD3OD, first-order-catalyst dependence is maintained. The entropy of activation reveals an organized transition state (−42.1 cal/mol·K) which would be consistent with the mechanism in

• involvement in proton transfer at the transition state [78]. In systems where protodemetalation is rate determining, a metal-carbon bonded intermediate is allegedly characterized, as in the case of a related palladium-catalyzed hydroamination [47], and a propargylamide cyclization [44]. In our studies, the

• less than half complete at the transition state [79]. In foundational work on alkene hydration by Evans and Kirby, a general acid-catalyzed mechanism is concluded, and small isotope effects are observed despite H–O bond breaking in the transition state [80]. In an excellent study by Borhan and co

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• undergo addition to the heterocyclic radical acceptor 19 through a ternary transition state 20 involving hydrogen bonding interactions with the chiral phosphate co-catalyst. Notably, a follow-up report revealed that the radical addition is reversible, and that the selectivity determining step involves the

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• experimental findings discussed earlier. Once INT 1 is formed, for the rest of the process, the TOF determining transition state (TDTS) of the process is α/β-TS 2 and the TOF determining intermediate (TDI) is INT 2 and the energetic span (δG) is 16.2 kcal·mol−1 for the α-attack and 17.0 kcal·mol−1 for the β

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• alternative mechanism, we envisionned a possible interconversion of 7 and 7’ through a [1,5]-sigmatropic rearrangement resulting in a hydrogen and cation shift towards 7’ (Scheme 4). To test this hypothesis, this rearrangement was computed at the DFT level. A cyclic transition state (TS) was found between

• oxocarbenium 7 and 7’ which exists as a stabilized form including an intramolecular stabilizing interaction between the carbocation and the ester carbonyl group. However, in close agreement with Hess and Baldwin’s values found for the rearrangement of cis-1,3-pentadiene [24], this transition state was high in

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• -Cs, the stabilization of this complex is significantly more important for the radical cation (around 20 kcal mol−1) than for the neutral complex (less than 10 kcal mol−1). To reach intermediate I-1, the singly-bonded dimer, a transition state TS-1 has to be overcome. The barrier for the radical

• distance is around 1.60–1.70 Å. Formation of the second C–C bond to yield dimer 1-Cs requires to overcome a second transition state TS-2 with energy barriers that range between 10–13 kcal mol−1 from the immediate intermediate depending on the profile. The interdimer C···C distance of the forming bond is

• differences, which corroborates the validity of our periodic approximation to study the dimerization of the radical cation inside the CNT (see below). The rate-determining transition state for the radical cation and for the neutral dimer is the same (TS2) as well as the lowest-energy intermediate (van der

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

• 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

• formation (Figure 1C) [12]. This intriguing mechanism of catalysis should be further intensified on single-walled carbon nanotubes 2 (SWCNTs, Figure 1D) and multi-walled carbon nanotubes 3 (MWCNTs, Figure 1E) [13]. Multiple substrate/transition-state binding should reduce particularly in-plane polarization

• of the π system and thus induced anion–π interactions. Since the polarization caused by substrate/transition-state binding hinders additional binding, this effect should occur only at high concentrations. These expectations were first explored with anion–π catalysis on fullerenes in 2017 [12

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• active-metal template strategies [12][13][14][15][16][17][18][19][20][21][22][23]. Other known methods are shrinking [24][25], swelling [26] or hydrogen-bond-mediated transition state stabilization [27][28][29], the latter resembling active-metal template synthesis. Regardless of the method used, the

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• endo-transition state A to give spirooxindole-pyrrolizidine 17 which spontaneously reacts with another equiv of arylaldehyde to form ylide 18 in the presence of zeolite HY. The second [3 + 2] cycloaddition of 18 with 14a affords product 15a as a major product through an endo-cycloaddition and 15a’ as a

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

• variexenol B without cation–π interaction. IM means intermediate and TS transition state. Potential energies (kcal/mol, Gibbs free energies calculated at the mPW1PW91/6-31+G(d,p)//M06-2X/6-31+G(d,p) level) relative to IM1 are shown in parentheses. (A) Results of the DFT evaluation of the whole pathway of

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• cyclization transformation involving activation of the electrophilic sulfur reagent by PhSePh with the assistance of TMSOTf to form transition state I. Intermediate II formed through capturing of sulfonium by selenium. Then, II reacted with 136 to give regioselective cyclic thiiranium ion III. Nucleophilic