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

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• coordination to Ni. The complex B regenerates after the conjugate addition via transition state C and coordination of a new β-ketosulfone molecule to Ni. TS1 and TS2 are proposed by analogy with 1,3-dicarbonyl compounds [47] to rationalize the asymmetric induction. As illustrated in Scheme 2, β-ketosulfone is

• nitroalkene in TS2-I and 2-II may also help to rigidify the transition state and improve the stereoselectivities. The observed (2R,3S)-diastereoselectivity in the presence of catalyst 7a stems from the addition of the Re face of the β-ketosulfone to the Si face of the nitroalkene in TS2-I. We suppose that the

• -Michael reaction of (2R,3S)-8a in chloroform-d solution. ORTEP diagram of (2R,3S)-8d. The proposed mechanism of asymmetric addition of β-ketosulfones to nitroalkenes. Transition state models for asymmetric addition of β-ketosulfones to nitroalkenes. Screening of Ni(II) complexes with chiral diamines in

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• formal syn-SN2’ reaction. This is an intriguing observation, since for other TSs a NPP-cyclisation by anti-SN2’ is usually described [40][45][46][47]. This cyclisation mechanism is thought to be the predominant case, giving rise to a more energetically favoured transition state, but occasionally also the

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• package [26]. The energies of all the structures are on the B3LYP/6-311G++(d,p) level, and the zero-point vibrational energy (ZPVE) corrections are all at the DFT level. Throughout this study, all the relative energies refer to the ZPVE-corrected energies. For the transition state (TS) between species A

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• 1,2-di(pyridin-4-yl)ethylene and 4,6-dichlororesorcinol in the transition state (Figure 24). Finally the cyclobutane derivative 43 was observed after the release of catalyst for the next cycle. In 2012, again the MacGillivray group reported an improved version of the above mentioned [2 + 2

• –tert-butylcalix[4]azulene through mortar and pestle grinding of the host and the guest. The structure of the complex was obtained from DFT study. Formation of a 2:2 complex between the supramolecular catalyst and the reagent in the transition state of the [2 + 2]-cycloaddition reaction of 1,2-di

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• dry dichloromethane resulting in the stereoselective formation of the corresponding β-isomer 17 of O-ethyl nicotinate riboside in high yield. It was speculated that less polar solvents, such as DCM, contribute to the formation of a less dissociated transition state, similar to F in Figure 3 above

• metal complex. The amide functionality in the 3-nicotinamide core plays a crucial role in the subsequent reduction because it coordinates with the metal center of the hydride complex, resulting in a favorable transition state which ensures the transfer of the hydride on the 4-C position of the

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• –base equilibrium, leading in situ to the formation of its conjugate base 8. This anionic intermediate 8 acts as nucleophile and reacts with bromoethane (9) in a, probably, bimolecular mechanism, through a pentacoordinate transition state 10 as represented in Scheme 2. The reaction occurs in a

• . Table 4 illustrates the optimized geometry for the transition states for each possible reaction path. The comparison of the two possible reaction paths shows that although N-ethylation of the carboxamide site is associated with a lower energy barrier, addition of solvent stabilizes the transition state

• optimized geometries provided the expected 180° angle for nucleophilic bimolecular substitution. In this regard, the transition state of the reaction with the carboxamide conjugate base provided a value of the N–C–Br bond angle about 2o greater than that of the reaction with the oxoquinoline anion, in all

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• , which is opposite at C2, was assigned by comparison of their computed and experimentally observed CD spectra [33][34]. To tentatively explain the observed stereochemical outcome in the absence of additional knowledge on the transition state of the rearrangement [36], two reactive conformers G and G

• of an aryl group at C4 but no additional details were provided. The high diastereoselectivity was explained by considering a six-membered chair-like cyclic transition state model TS3 in which the substituent at the α position of the ester (C4) preferentially occupies a pseudo-equatorial position

• nature of the rearrangement (Scheme 10) [33][34]. The acidic promotor may be simply assisting the dissociation of the C4–O bond in the transition state TS3 whilst an aromatic group (R1 = Ar) would contribute to the stabilization of a developing positive charge at C4. The [3,3]-sigmatropic rearrangement

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• energies are (Ea) in kcal mol−1 and italic. Transition state leading to 8eq following front1 attack (Ea = 32.6 kcal mol−1, Figure 5, Table 3, entry 1). Breaking and forming bonds in dashed lines, additional C–H-interactions with dotted lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d) at 298 K

• ). Transition state leading to 8ax following front2 attack (Ea = 33.2 kcal mol−1, Figure 5, Table 3, entry 2). Breaking and forming bonds in dashed lines, additional C–H-interactions with dotted lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d) at 298 K). Transition state leading to 8eq following

• side attack (Ea = 37.4 kcal mol−1, Figure 5, Table 3, entry 3). Breaking and forming bonds in dashed lines, additional C–H-interactions with dotted lines (M06-2X-D3/6-311++G(d,p)(PCM=THF)//B3LYP-D3BJ/6-31G(d) at 298 K). Transition state leading to 9 following side attack (Ea = 31.4 kcal mol−1, Figure 5