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

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• 63a induced an energetically-disfavoured twist in the fluorine adduct’s conformation (INTA’), raising its energy over that of 63b and decreasing the energy barrier between it and the reductive elimination transition state TSA’. Additionally, the role of the halogen bond acceptor in 61d is also poorly

• - and hydrogen intermolecular bonds. This adduct decomposed by reductive elimination of the iodoarene via a three-membered transition state (TS), coupling the syn thioamide and β-dicarbonyl ligands to give thiocarbenium ion 74. The authors determined similar activation energies (≈20 kcal/mol) when

• derived iodonium ylides 63a and 63b. Proposed equilibration of intermediates to transit between 64a (the initial adduct formed between 61d and fluoride) and 64c, to properly situate fluorine for reductive elimination. X-ray crystal structure of dimeric 39 [6], (CCDC# 893474) [143][144]. Transition state

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

• the reaction partners in a highly ordered three dimensional transition state through noncovalent interactions (like H-bonding, π–π interactions) thus promoting the stereoselective reaction. Examples of covalent bonding organocatalysts are amines [6][7], N-heterocyclic carbenes [8][9], phosphines [10

• performs as an H-bond donor towards the imidazoline nitrogen and the electrophile acts as H-bond acceptor from the OH group of the catalyst. These interactions rearrange the three molecules in a chiral pocket as shown by transition state 7, favoring stereoinduction in the products through C3

• enantioselective aza-Friedel–Crafts addition. In the first step, the DDQ-promoted oxidation of 3-indolinonecarboxylate 22 generated indolenines that performed as the potential electrophiles towards indoles 4. The chiral catalyst effectively assembled the reacting partners in a chiral transition state through H

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• functional with D3 Grimme’s dispersion correction [42][43] and 6-311++G(d,p) basis set. All reported minima and transition state structures were confirmed by calculation and diagonalization of their Hessian matrices. The reported energies are Gibbs free energies calculated with the SMD method in N,N

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• diastereocontrol originates from the preferred E/Z enolate geometry during the transition state. Interestingly, using t-BuOH instead of iPrOH resulted in exceptionally better results for some substrates with different ring sizes. In 2015, the group of Feringa investigated the copper-catalyzed conjugate borylation

• desymmetrization step during which the chiral enolate attacks (Si-face) the prochiral cyclohexadienone ring via a chair-like transition state. The reaction requires an excess amount of base, resulting in the formation of a more favorable lithium enolate. Subsequent oxidation of the boronates gave the corresponding

• >20:1). Due to the high diastereoselectivity, the authors have concluded that the boron enolates are stable and do not isomerize by reversible formation of C–boryl species. The stereochemical information of the enolate is most likely transferred to the final product via a chair-like transition state

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• to the transition-state energy. However, the problem is that the transition state is rather specific and dependent on the particular reaction type. Thus, it hardly can be generalized. In contrast, the thermodynamically controlled stereoselectivity refers to the difference in the thermodynamic

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• adds to the diazo compound 5 under formation of zwitterionic Int1 (ΔG = 5.2 kcal/mol). Afterwards, copper carbene complex Int2 is formed after extrusion of nitrogen. The transition state of this metal carbene formation TS1 was calculated with an activation free energy of 16.4 kcal/mol (Scheme 5). Int2

• adds to styrene to the carbon atom in 2-position of the ethenyl group. At this point, four different orientations of the phenyl group are conceivable (Scheme 6 and Scheme 7, TS2_1 to TS2_4). After an early transition state with hardly any activation barrier, the addition of styrene to Int2 proceeds in

• then involved in the next catalytic cycle and thus removed from the equilibrium between Int4 and Pr + CuI. In addition, since TS2 is an early transition state and the potential is concomitantly very flat, only TS2_2 was found by means of regular optimization towards a first order saddle point. For the

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• than the possible syn-1,4-substituted product. It was found the reductive elimination transition state leading to the 1,4-disubstituted product TS33-P1 would require an increase in distortion energy compared to TS35-P2 which contributes to an overall greater kinetic barrier. The following year, Lautens

• (Scheme 19) [62]. Similar reactivity trends were observed in both accounts. Mechanistically, the transformation was proposed to begin with the coordination of Cp*RuI to the exo face of the bicyclic alkene. Oxidative addition into the C–O bond, which is proposed to be the enantiodetermining transition

• state, followed by coordination to the alkyne generates intermediate 109. Migratory insertion of the alkyne results in the ruthenacycle 110. Subsequent reductive elimination generates putative allyl vinyl ether 111 and regenerates the active ruthenium complex. The allyl vinyl ether intermediate

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• (3+ + 2) reaction in which distortion effects are crucial for achieving the required ion-pair geometry in the transition state. Following this precedent, we proceeded to calculate the energy barriers and the corresponding activation parameters for all the reactions illustrated in Scheme 1 (series a–k

• the reagent the higher is the barrier (for similar transition-state energies) justifying the observed reactivity. Only the two systems (a and b) with lower values of the integration parameter have barriers compatible with observed reactions upon heating, the rest presenting too high barriers to allow

• dotted traces refer to lone pairs (monosynaptic basins) and colored plain traces to bonds (disynaptic basins). The vertical red line indicates the transition state (see Supporting Information File 1 for the full data). Quantitative NCI analysis [36] for the reaction of series a–f leading to fused

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• -induction of the aldol stereocenter by β-alkoxy ketone 9, leading to an (S)-configuration [18][19][20]. This control is supposed to follow a boat transition state A stabilized by a formyl hydrogen bond [30]. It is known to be dependent on the nature of the β-alkoxy substituent, being particularly favoured

• by the PMB and other aromatic groups, while being disfavoured by silyl protecting groups. Alternatively, an (R)-configuration of C-15 could result from a polar Felkin–Anh model controlled by aldehyde 8 through chair-transition state B [14][15][16]. To determine the configuration of C-15, we initially

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• kinetic and computational analyses, the B‒C(sp2)/B‒H transborylation transition state was determined to have a free energy barrier of approximately 20 kcal mol−1 (ΔG‡calc = 19.7 kcal mol−1; ΔG‡exp = 20.3 kcal mol−1) (Scheme 2). The borane-catalysed hydroboration of alkenes has been less explored, with

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• conformation of the transition state. A chair transition state is less preferred because of inherent non-bonding interactions of some hydrogens. This has been discussed in detail in the original publication by Taber and Gunn, favoring 9 as the main diastereomer [13]. Our results confirm these data. To increase