Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• from the directing group. This was attributed to the importance of both the negative charge at the carbon and the forming C–Cu bond being developed in the transition state, which is stabilized by the positive charge on the carbon bearing the directing group. Later, in 2017, the same group investigated

• addition of benzylic–Cu intermediates to imines proceeds through a flexible linear transition state which is sensitive to the steric environment surrounding the copper catalyst. This observation provided the opportunity to achieve either diastereomer depending on the choice of the ligand L45 or L46. Based

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• the carbonyl oxygen to I gives intermediate II, which undergoes an aryl-transfer reaction via a Heck-like four-membered-ring transition state III to form the intermediate IV with Cu(III) and aryl group added at the C8- and C7-positions of the naphthalene ring, respectively. Finally, the breakdown of

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• . From there, dissociation of the N–O bond starts to take place and proceeds uphill through a transition state, T1(TS), the structure of which was optimized fully. Vibrational analysis gives a single imaginary frequency (−550.12 cm−1) which corresponds to the N–O bond stretching confirming that the

• (TS) is reflected in the low value of the activation entropy, ΔS≠ = 0.474 cal/mol∙K, which means that there is a very small disorganization in the transition state as compared to the reactant in the T1 minimum state. The length of the bond N–O in the transition state is equal to 1.629 Å. The

• the bond under dissociation, that is, the N−O bond which constitutes the potential well. In Equation 4 Q≠ and QR represent the molecular partition functions in the transition state and in T1 min with their values being 0.241907∙1024 and 0.184606∙1024, respectively. Additionally, Equation 5 was used to

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• organometallics in solution resulting in mixtures of the two reagents [15]. Thus, upon reaction with an aldehyde, mixtures of propargylic and allenic alcohols can be obtained through a chelate transition state (SE2'). Attempts to improve the regioselectivity of the propargylation reaction by using allenic

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

• 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

• model (PCM). Vibrational frequencies for all of the optimized structures were calculated to ensure the presence of a single imaginary frequency for each transition state, and the absence of imaginary frequencies for reactants, intermediates, and products and also to obtain thermal corrections for

• anion Int1 by hydride addition to the terminal carbon atom of the isocyanide group in 2a via transition state TS1. This anion undergoes nucleophilic addition to the thiocarbonyl moiety of the xanthate 1a to generate the intermediate Int2 via transition state TS2. In the next step, elimination of the

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• , according to calculations. The reason of this behavior was most probably the cyclic structure of the intermediate. However, if the intermediate I can undergo a second protonation process, intermediate III forms through transition state II. Water elimination from III proceeded with slight increase in energy

• , affording intermediate IV, which may undergo two different transformations: The first transformation involves dissociation of a water molecule, which leads to the formation of the dication IX through transition state VIII. Taking into account that all energy barriers were well below 10 kcal/mol, it seemed

• formed dication V underwent an intramolecular nucleophilic substitution through transition state VI, which proceeded with a small activation barrier, leading to the cyclic intermediate VII and further to the rearranged product 54. The tentative mechanism discussed above does not explain the formation of

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• active site cluster model. The results revealed the significant effect of the active site residues on the relative electronic energy of the intermediates and transition state structures with respect to gas phase data. A detailed understanding of the role of the enzyme environment on the CotB2 reaction

• potential. Additionally, structural analysis revealed that each cation was stabilized by noncovalent interactions, such as π–cation and dipole–cation interactions. A comparison of the transition state structures in the gas phase vs the active site model is shown in Table 2. These findings suggest that the

• residues. Comparison table of transition state structures in gas phase vs active site model. Supporting Information Supporting Information File 180: Cartesian coordinates for all species. Funding This work was supported by the Israeli Science Foundation (Grant no. 1683/18).

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

• derivatives. These intermediates will be of value for their future conversion into transition state analogues as well as for the introduction of various lipid extensions at the anomeric phosphonate moiety. Keywords: antibiotic resistance; glycosyl phosphonate; glycosyl transferase; lipid A

• compounds to allow for future incorporation of different lipid chains and options towards glycal analogues as potential transition state analogues to inhibit 4-amino-4-deoxy-ʟ-arabinose transfer to bacterial LPS. Results and Discussion The previously synthesized [14] methyl 4-azido-4-deoxy-α-ʟ

• signal of the anomeric OH group at 5.79 ppm. Next, the ensuing elimination step was carried out to explore the access to transition state analogues [22] potentially mimicking the sp2 character of the oxocarbenium intermediate in the enzymatic transfer reaction. In addition, exo-glycals are versatile

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• attributed to a steric clash between the methoxy groups in meta-position to the azo double bond and the six-membered morpholino ring [9]. The rapid thermal reversion was attributed to the removal of two ortho-methoxy groups, leading to diminished steric strain in the transition state for reversion [9]. In

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• and iodobenzene. In pathway b, the O–I intermediate C is converted to a C–I intermediate D via 1,3-migration [89]. Then, intermediate D carries through a five-membered ring transition state F to afford the title product 2a, accompanied by the release of iodobenzene and water. One practical application

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

• rearrangements of O-allyl β-ketoesters [35][36][37]. Hiersemann and Strassner studied the Claisen rearrangement with H-bond-donating organocatalysts by computational methods and concluded that thioureas are not efficient in transition-state stabilization [38]. Regarding the usefulness of the Ireland–Claisen

• Schreiner thiourea (C12) had higher activation barriers for both isomers (111.9 kJ·mol−1 for (E) and 95.6 kJ·mol−1 for (Z)). These results suggest that Schreiner thiourea binds stronger to starting silyl ketene acetal than to the corresponding transition state. Therefore, it stabilizes more the starting

• material than the transition state, which results in the slow-down of the reaction (Figure 3). Similar trends were observed also for diphenylthiourea and a squaramide (Figure 4). Using the structures optimized at the ωB97X-D/6-31G* level of theory we calculated interaction energies between catalysts and

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• of the transition state for the hemi-indigo derivatives. Therefore, a highly ionic medium can stabilize the transition state of the hemi-indigo leading to the decrease of the energy barrier between Z- and E-isomers and, therefore, reducing the half-life of the E-form. However, further studies are

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

• paper [18]. Briefly, the different possible pathways for thermal Z–E isomerization were calculated, and each process was weighted by the relative Z-isomer ground state energy and transition state (TS) energy barrier for all possible conformers (see Experimental for details). Focusing first on the 4pzH

• 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

• , or destabilizes it, via steric clashes. In contrast, these effects are significantly diminished for the transition state geometry (Figure S3 in Supporting Information File 1), at which the pyrazole moiety and the ortho groups remain far apart. A particularly interesting case in point are the 4pzH-Pyr

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• 66 (Scheme 26). Galvanostatic electrolysis of 66 in an undivided cell using a catalytic amount of 67 resulted in the corresponding lactones 68 in moderate yields and good stereoselectivities. The stereoselectivity was proposed to be controlled through the preferential formation of transition state A

• over B after reaction of the enolates of 66 with chiral iodoarene 67. Steric factors restrict the formation of transition state B, and the reaction preferentially proceeds via transition state A to stereoselectively form the lactones [62]. Chiral catalysts Achieving enantiocontrol in electrochemical

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• computations on carbocation intermediates and transition states were carried out with the B3LYP functional and 6-31+G(d,p) basis set, using the polarizable continuum model in dichloroethane to model solvation [42]. Each stationary point was characterized as a minimum or transition state by vibrational

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• Diels–Alder transition state, whilst those which were electron-withdrawing (e.g., NO2, CN, NMeAc) decreased the reaction rate. Interestingly, strong EDG (e.g., OMe, NMe2) exhibited a slower reaction rate than predicted, but this is likely due to the increased stabilisation of the reactant, rather than

• the transition state [71]. Fulvenes can be quite sensitive to oxygen, which has been documented for pentafulvenes and heptafulvenes [16][47][54][55][95]. Pentafulvenes have been reported to react with both ground (triplet) [51][52][55] and excited (singlet) state oxygen [7][49][50][53] resulting in

• cycloaddition proceeds through an ambimodal [6 + 4]/[4 + 6] transition state leading to both of the proposed [6 + 4] adducts, which can interconvert through a Cope rearrangement (Scheme 6) [107]. Dimerisation cycloadditions Generally, dimerization of fulvenes is an undesired process that may occur upon storage

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• transition state (TS, see Supporting Information File 1, Table S8). In the B3LYP computations this value is larger than for the corresponding Z-isomer and leads to a stabilization of the TS in polar solvents [46]. The bistable character is obviously weakened upon improving the halogen bonding properties

• computed using the KistHelp program [49] employing classical transition state theory and including the effects of Wigner-tunnelling (Supporting Information File 1). Supporting Information Supporting Information File 90: General experimental information, synthetic procedures, UV–vis photochemistry and

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• . All energies are shown in kcal/mol. The Y axis shows the carbon number and the X axis shows the coordinate in the heat map. The right structural heat map shows the total mobility in tricycle formation. Red means high mobility, yellow means moderate mobility, and blue means static. TS: transition state

• and the X axis shows the coordinate in the heat map. The right structural heat map shows the total mobility. Red means high mobility, yellow means moderate mobility, and blue means static. TS: transition state. Energy diagram and heat map analysis of ring rearrangement (A) IM6e–IM11 in quiannulatene

• means high mobility, yellow means moderate mobility, and blue means static. TS: transition state. The regio- and stereoselectivity in quiannulatene and sesterfisherol biosynthesis are determined by the initial conformation of GFPP. Reaction mechanism of quiannulatene biosynthesis. GFPP: geranylfarnesyl

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• Figure 3 are M062X/6-311+G** calculated structures and energies of cations 27 and 24, which are distinct energy minima, along with the transition state 28 which connects these two cations. Cation 27 derives most of its stabilization from the phenyl group, while the TMS group in the 3-position provides no

• of cation 37. This study at the B3LYP/6-31G* level suggested that migration of bond a in 43 is not viable since the resultant cation 47 is not an energy minimum at this level, but a transition state. However, a current study at the M062X/6-311+G** level finds that both conformations 47a and 47b are

• potential rearranged cation 81 (E = CN) is not even an energy minimum, but a transition state. Conclusion 1-Substituted-cis-2-trimethylsilylyclopropylcarbinyl mesylates and triflates 13 solvolyze in CD3CO2D to give products derived from 3-trimethylsilylcyclobutyl cations. These cationic intermediates are

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• transition state was involved. Acid-induced aziridine ring openings and subsequent conjugate additions to the α,β-unsaturated lactone led to the formation of cis-fused [5,5']bicyclic compounds 186a or 186b. Reduction of the lactone moiety in 186a and subsequent deprotection gave (2S,3R,4S,5R)-184. In order

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• , the proposed asynchronous concerted mechanism. A deeper analysis of the full path of the reaction using MD calculations [29] would be needed in order to assess the synchronicity and life time of transient species [30]. The recent use of MD simulations has demonstrated that a single transition state

• in a reaction with an only transition state in which a planar transient species is developed during the reaction [38]. The formation of transient carbocations developed along the reaction course cannot be detected by the calculation of stationary points alone. The use of topological methods, in

• mechanism consisting of a (3 + 2) transition state has been confirmed as the preferred one [25], we restricted the study to this approach. Computational Methods The procedures are analogous to those previously reported [43]. All of the calculations were performed using the Gaussian 09 program [47

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• reactants. In fact, encapsulation can result in the stabilization of a specific transition state by stripping it out from solvent molecules [13][14]. Hence, in aqueous medium, the syntheses of nanoreactors with a covalent organic framework is important, which is indeed a difficult task due to their large

Cyclobutane dication, (CH₂)₄²⁺: a model for a two-electron four-center (2e-4c) Woodward–Hoffmann frozen transition state

• G. K. Surya Prakash and
• Golam Rasul

Beilstein J. Org. Chem. 2019, 15, 1475–1479, doi:10.3762/bjoc.15.148

• considered as a prototype for a 2e-4c Woodward–Hoffmann frozen transition state. The planar rectangular shaped structure 2 with a 2e-4c bond was found not to be a minimum. Keywords: cyclobutane dication; 2e-4c bond; frozen transition state; Woodward–Hoffmann rule; Introduction The protonated hydrogen

• carbodication containing a 2e-4c bond and can be considered as a prototype for a frozen Woodward–Hoffmann transition state analog [12][13]. The 2e-4c delocalized σ-bishomoaromatic system is representative of a 2e-aromatic pericycliclic species. This type of system may be considered as the transition state of

• points as minima (NIMAG (number of imaginary frequencies) = 0 or transition state NIMAG = 1) and to compute zero point vibrational energies (ZPE), which were scaled by a factor of 0.96 [15]. CCSD(T)/cc-pVTZ optimizations and GIAO-CCSD(T) 13C NMR chemical shifts calculations by the GIAO (Gauge Invariant

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• ][42]. From the results we so far gained, a migratory order could be assessed for the present reaction: Bu ≥ EDG-substitued Ar > EWG-substitued Ar ≥ Ar ≥ benzyl > allyl, and it appears that the larger the other substituents on the boron atom are, the easier the transfer is. A possible transition state

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• these premises, two transition states can be identified (Figure 4) for the hydroboration reaction on each of the two diastereotopic faces of the double bond. The transition state deriving from the attack on the si face, which leads to the arabino-configurated product, contains two destabilizing

• pseudoaxial substituents. The alternative, a more stable transition state formed from the re-face attack would bear to the actually obtained 3S configurated boronic acid analogue 7. The final deprotection of compound 7 by conventional catalytic hydrogenolysis gave the final compound 8 in almost quantitative