Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• superacidic CF3SO3H leads to cyclization or arylation products, depending on the presence or absence of benzene. A mechanism is proposed involving tetra-, penta-, and hexacationic reactive intermediates. Most notably, this system shows remarkably good chemoselectivity in its reaction with benzene (only

Mechanochemical Friedel–Crafts acylations

• Mateja Đud,
• Anamarija Briš,
• Iva Jušinski,
• Davor Gracin and
• Davor Margetić

Beilstein J. Org. Chem. 2019, 15, 1313–1320, doi:10.3762/bjoc.15.130

• transient reactive intermediates were predicted by density functional theory method B3LYP/6-31G* (Supporting Information File 1) [61]. The stretching of the +C≡O bond of the acylium ion was predicted to be at about 2300 cm−1. Raman spectroscopy revealed that the complexation of phthalic anhydride with AlCl3

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• -centered radicals (NCRs) are attractive reactive intermediates for organic synthesis as they provide opportunities for the efficient construction of C–N bonds [15][16][17][18][19]. Recently, the generation of NCRs through electron transfer-based methods has been attracting attention. Organic

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• intermediates mimic single steps of the proposed catalytic cycle in the gas phase. Thus, the charge-tagged catalyst proved one more time its superior effectiveness for the detection and study of reactive intermediates at low concentrations. Keywords: charge-tag; electrospray ionization; enamine organocatalysis

• species that are not involved in the reaction and do not carry the charge-tag will have a much lower ESI response. A charge-tag thus facilitates “fishing” [5][23][28] for reactive intermediates. We have previously used the charge-tagged L-proline derived catalyst 1∙Cl (Figure 1) in an ESIMS study of a L

• ) in the reacting solution. In order to enhance the ESI response of putative reactive intermediates, the reaction was performed with the charge-tagged tetrazine 4∙Br (R2, Scheme 5). A continuous-flow setup [4][17][18] was used for fast sampling of the reaction R2 directly after its initiation. A

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• given to domino reactions with an oxidation step, revealing possibilities for shifting the equilibrium by making products more stable or in situ generating reactive intermediates [2][3][4][5][6][7][8][9][10][11][12][13]. In its turn, multicomponent reactions (MCRs), usually occurring as domino processes

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• 57, which were used to connect with site-directing ligands [89] (Scheme 9). As reactive intermediates, o-QMs can also play the role of monomers in polymerization reactions. Ishida et al. reported the ring-opening polymerization of monofunctional alkyl-substituted aromatic amine-based benzoxazines [90

• ]. It was shown that the methylene bridges can be formed by o-QMs that are resulted by the cleavage of phenolic Mannich bridge structure 56 (Scheme 9). Biological properties As discussed earlier, o-QMs are known as short-lived, highly reactive intermediates. Therefore, their biological activity is

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• by deconvolution of the line shapes and subsequent integration. Possible reactive intermediates for C–F activation of benzyl fluoride 1 with strong hydrogen bond donors. Synthesis of enantioenriched 7-[2H1]-(R)-benzyl fluoride ((R)-1) from benzaldehyde (2). Synthesis of enantioenriched (S

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• anhydrides as reactive intermediates blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones are formed by consecutive pseudo three-component syntheses in a one-pot fashion. The Stokes shifts correlate excellently with the Hammett–Taft σR parameter indicating an extended degree of resonance stabilization

• , sensing and display applications [41]. 4-Phenylnaphtho[2,3-c]furan-1,3-diones can well serve as reactive intermediates in multicomponent reactions, e.g., for synthesizing the corresponding imides. A particularly intriguing access to 4-phenylnaphtho[2,3-c]furan-1,3-diones is the intramolecular [4 + 2

• , leaving the anhydride unimpaired. For employing 4-phenylnaphtho[2,3-c]furan-1,3-diones 2 as reactive intermediates for the en route conversion with primary amines 3 into 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones 4 the reaction conditions were optimized with 4-phenylnaphtho[2,3-c]furan-1,3-dione (2a) and

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• method where both the glycosyl donor and the acceptor are present when the promoter is added, preactivation can generate reactive intermediates as the resting state allowing spectroscopic analysis such as low temperature NMR studies to better characterize the intermediate. This can help gaining a deeper

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• and biological properties [26][27]. Organoperoxides have wide applications in the field of organic synthesis, as radical initiators, oxidants that replace transition metal oxidants, and key reactive intermediates in diverse organic synthesis reactions [28][29][30], as well as in medicinal chemistry

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• reactions were performed which has led to the discovery of reactive intermediates, new phases and novel topologies in systems previously studied only by ex situ analyses [25][26]. To overcome the inability of PXRD to provide structural information on amorphous materials, a method based on real time in situ

• 27, it has been explicitly stated in the literature that these compounds are very reactive intermediates and immediately decompose to isothiocyanates and 1H-benzotriazole (HBt). With this in mind, we investigated the possibility to run the thiocarbamoylation reaction of para-substituted anilines as

• synthetic tool that enables the synthesis and isolation of molecular species as bench-stable chemicals, that are normally considered as reactive intermediates in solution environment. The observed reactivity of thiocarbamoyl benzotriazoles prompted us to examine their reaction with ammonia, as a potential

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• asymmetric α-amination reactions [145]. By using hydroxylamines 43 as simple N-containing reagents, the addition of these compounds to trichloroacetonitrile gives the reactive intermediates 44, which then serve as versatile electrophilic N-transfer reagents under asymmetric triazolium salt L catalysis

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

• Yuta Isoda,
• Norihiko Sasaki,
• Kei Kitamura,
• Shuji Takahashi,
• Sujit Manmode,
• Naoko Takeda-Okuda,
• Jun-ichi Tamura,
• Toshiki Nokami and
• Toshiyuki Itoh

Beilstein J. Org. Chem. 2017, 13, 919–924, doi:10.3762/bjoc.13.93

• pathway [30]. Although it is hard to exclude another reaction mechanism involving oxocarbenium ions as reactive intermediates, the commonly accepted reactivity difference between α- and β-isomers of glycosyl triflate 3 seems to explain the observed selectivity well. Next, we attempted to synthesize the

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• study protonated forms of the oxadiazoles as reactive intermediates by means of NMR and DFT calculations. It should be noted, that the metal-catalyzed hydroarylation of C=C bonds is widely used in organic synthesis [26][27]. The most efficient catalysts for these purposes are complexes of the transition

• species D. Thus, the NMR data reveal that the protonation of 5-styryl-substituted 1,2,4-oxadiazoles in superacids results in the formation of their relatively stable N4-protonated forms. However, these species do not react with aromatic π-nucleophiles (vide infra). Most probably, those reactive

• intermediates, generated under the protonation of substrates 1, are N4,C-diprotonated species D. The experimental results from the hydroarylation reactions of the side chain C=C double bond of oxadiazoles 1a–n with various arenes under the action of different acidic reagents leading to oxadiazoles 2a–za are

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• chemical processes that are difficult to perform under batch conditions, e.g., involving reactive intermediates or competitive reactions [74][75]. Compared to batch setups, performing reactions under continuous flow allows a fine tuning of the contact time between intermediates and catalytic active phase

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• of the channels, volume), and on the flow rate. The residence time is one of the crucial factors to be considered in optimizing flow reactions, especially when unstable or short-lived reactive intermediates are concerned. Microreactor technology provides also several benefits. Safety benefits

• the possibility to generate highly reactive intermediates, such as halomethyllithium carbenoids, that need to be used under internal-quenching technique in batch mode. In 2014, the first example of effective external trapping of a reactive chloromethyllithium (CML) has been reported [28]. α

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• intermediate, delocalized diradical species. The influence of selenium as a ‘heavy atom’ for stabilization of this intermediate has been emphasized. Keywords: 1,3-dipolar cycloadditions; reaction mechanisms; reactive intermediates; thiocarbonyl S-methanides; thioketones; Introduction Thiocarbonyl S

• -methanides 1 belong to the class of S-centered 1,3-dipolar species, which were identified by Huisgen as reactive intermediates formed via nitrogen extrusion from 2,5-dihydro-1,3,4-thiadiazoles 2 [1][2]. In spite of the fact that several methods are reported for the preparation of these precursors, the most

• with solvation effects (assuming ∆H(solv) = ∆G(solv)) to obtain enthalpies at 298 K in THF (Equation 1). The calculated entropy was used to determine the –T∆S term to form free energies at 298 K in THF (Equation 2). Structures of the reactive intermediates as a diradical 6 or a zwitterion 7 in the

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• -on-a-chip approach. Kinetic and mechanistic studies The rapid analysis produced in flow NMR can be used for the detection of reactive intermediates and consequently for studying reaction mechanisms and the rapid optimization of a chemical process. The first example was described by Nakakoshi et al

Green chemistry

• Luigi Vaccaro

Beilstein J. Org. Chem. 2016, 12, 2763–2765, doi:10.3762/bjoc.12.273

• the safety of a chemical procedure, but also the proper selection of solvents, starting materials, and technologies used to generate and control reactive intermediates. In addition, the need for minimizing toxic waste and the respective disposal cost highlights how crucial it is to consider the

Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

• Dmitry S. Ryabukhin,
• Dmitry N. Zakusilo,
• Mikhail O. Kompanets,
• Anton A.Tarakanov,
• Irina A. Boyarskaya,
• Tatiana O. Artamonova,
• Mikhail A. Khohodorkovskiy,
• Iosyp O. Opeida and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 2125–2135, doi:10.3762/bjoc.12.202

• (Scheme 1). All species A, B, C, and D may play a role as reactive intermediates derived from 1a and 2 in superacids. To estimate the electrophilic properties of cations A, B, C, and D we performed quantum chemical calculations by the DFT method (Table 1). HOMO and LUMO energies, global electrophilicity

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• reactive intermediates. Three important types of enantioconvergent catalysis are specifically discussed herein: type I – stereomutative, type II – stereoablative [8], and type III – parallel kinetic resolution [9]. The primary criteria for all enantioconvergent catalytic reactions are: The starting

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• ; transition-metal-catalyzed reactions; Wolff rearrangement; Introduction Transition-metal-catalyzed reactions of diazocarbonyl compounds (DCC) with different organic substrates comprise a powerful tool of organic synthesis [1][2][3][4][5][6][7][8]. Of prime importance was found to be the ability of reactive

• intermediates generated from diazo compounds (ammonium, oxonium, C=X-ylides and others) to react with a variety of electrophiles/nucleophiles yielding complex and challenging organic molecules from relatively straightforward initial compounds [9][10]. The research group by Hu and co-workers elaborated recently

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

One-pot synthesis of 4′-alkyl-4-cyanobiaryls on the basis of the terephthalonitrile dianion and neutral aromatic nitrile cross-coupling

• Roman Yu. Peshkov,
• Elena V. Panteleeva,
• Wang Chunyan,
• Evgeny V. Tretyakov and
• Vitalij D. Shteingarts

Beilstein J. Org. Chem. 2016, 12, 1577–1584, doi:10.3762/bjoc.12.153

• -coupling; cyanoarenes; reactive intermediates; reductive alkylation; Introduction Alkylcyanobiphenyls are well known largely due to their mesogenic properties, which were discovered by Gray in the 1970th [1][2]. Alkylcyanobiphenyls and their analogs (e.g., dialkyl and alkoxy alkyl derivatives) are still