Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• was achieved by increasing the reaction time and acidity of the reaction medium, while elevated temperature showed no effect (Scheme 3) [40]. The mercuricyclization was also employed in the field of carbohydrate chemistry for the synthesis of α-ᴅ-C-glycopyranosyl derivatives. The reaction between

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• other hand, such electron-withdrawing groups, α to the reactive centre, dramatically changes the acidity of the substrate (and thus the reactivity of the enolate conjugate base) and as consequence its reactivity which can drastically impact the enantioselectivity in SN2 alkylation processes. In this

• reactive centre dramatically increases the acidity at this position and, in preliminary studies, we found that under biphasic basic conditions 2-oxindole 5 was undergoing alkylation also in the absence of a phase-transfer catalyst (not ideal when designing a catalytic enantioselective process). Despite

• reactions can be occasionally performed even in absence of base under water-enriched/organic biphasic conditions [41][42][43][44][45][46][47]. Taking inspiration from these studies, it was envisaged that by employing base-free neutral reaction conditions – given the likely acidity of substrate 5 – that it

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• triphenylphosphine (TPP) in catalyzing oxa-Michael additions. A matrix consisting of three differently strong Michael acceptors and four alcohols of varying acidity was used to assess the activity of the three catalysts. All test reactions were performed with 1 mol % catalyst loading, under solvent-free conditions

• more electron-rich catalysts is less pronounced. The experimental activity trend was rationalized by calculating the Michael acceptor affinities of all phosphine–Michael acceptor combinations. Besides this parameter, the acidity of the alcohol has a strong impact on the reaction speed. The oxidation

• triarylphosphines TPP, MMTPP and TMTPP as catalysts for the oxa-Michael reaction three varyingly strong Michael acceptors, namely acrylonitrile (1), acrylamide (2) and divinyl sulfone (3) were reacted with four different alcohols of similar molecular mass but different acidity (Figure 1). The stoichiometry of

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• developed by Widenhoefer [25][29] relied heavily on the acidity of the carbonyl substrate, and this hampered the use of less enolizable substrates, like alkenyl β-ketoesters. The same group addressed this limitation by proposing the use of trimethylsilyl chloride (TMSCl) as an additive in the intramolecular

• hydroalkylation cascades. In 2016, the Cui group reported the hydroalkylation of olefins 59 using p-quinone methides 60 as electrophilic partners (Scheme 24A) [91]. Alkenyl alcohols could be employed without needing to protect the hydroxy functional group, and the acidity of the phenolic hydrogen present in the

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• (4.8) were all too weak. While these results seem to make sense, when we compare the pKa values, they do not explain why a mixture of nitric and sulfuric acids causes rearrangement. It is possible that we are comparing the wrong values. pKa measures acidity in water. Under our reaction conditions it

• might better to compare the Hammett acidity function, H0, as this is more suitable for concentrated acids. On this scale triflic acid H0 = −14.1, perchloric acid H0 = −13, and sulfuric acid H0 = −12.0 are more similar and might explain why nitration conditions cause rearrangement [67]. Alternatively

Valorisation of plastic waste via metal-catalysed depolymerisation

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

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• 3) [229]. Based on infrared studies, the higher catalytic activities of the metallated ILs was attributed to their higher Lewis acidity compared to both the metal-free catalysts and the metal salts. A mechanism was therefore proposed in which a synergistic effect of the metallated ILs takes place

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

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

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• either the leaving ability of the oxindole nitrogen (R1: Cl, NO2) or the acidity of the >C=NH2+ group (R2: Cl, CF3) increasing the proportion of the nucleophile >C=NH, then the formation of the thiazole (route a) is further accelerated (Scheme 2). Although the addition of a base generates the required C3

• fulfilled – i.e., the substantial acidity of a hydrogen at C3 and a more stable α-thioiminium group necessary for the internal nucleophilic addition giving the thiirane intermediate (route b). It is well known that the acidity of carbon acids in acetonitrile is much lower than in polar aprotic solvents

• methanol) such an increase of acidity should be also distinct but it is known that polar protic solvents much better solvate anions and thus decrease their nucleophilicity. Therefore, dimethylformamide has been chosen as the best solvent. Indeed, when dimethylformamide (DMF) was used as the solvent for the

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• this effect is not fully clear. It might be linked to the electrophilicity of the carboxylic acid moiety that experiences an electron-withdrawing effects from the fluorine atom (see the comparison of the acidity in Table 2) [58]. In another study, tRNAPro was preloaded with proline analogues, and a

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• nonfluorinated analogues (Eox (PhNMe2) = +0.71 V (SCE)), the radical cation 180 is formed under the reaction conditions, and deprotonation at the methylene unit near the CF3 group is highly favored because of the higher acidity, accounting for the observed high regioselectivity. In addition, the transient

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• -assembly in this study: pelargonidin chloride (Flavy), 1-naphthol-3,6-disulfonate (1N36S, photoacid), and poly(allylamine). The photoacid hydroxy group acidity increases upon photoexcitation. Flavy can undergo different reactions as given in Scheme 1. Poly(allylamine) is present in the protonated form as a

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• anion as a base (Figure 6). In fact, the abstraction of the hydrogen atom in the position adjacent to Au (C3) shows a low activation barrier (TS8, ΔG‡ = 12.6 kcal⋅mol−1) from the corresponding precomplex, leading to the formation of the intermediate XI and triflic acid. The high acidity of the latter

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• ), 40 wt % PW on silica (Table 1, entry 9), a 30 wt % PW loading on montmorillonite K30 clay (Table 1, entry 11), and a 40 wt % PW loading on alumina (Table 1, entry 12). The study on the optimal reaction conditions shed a light on the acidity and the physical characteristics required for the reaction

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• with the 3’-OH group, due its higher acidity [29]. For modified nucleosides, the preference of 2’-O-TBDMS formation in the presence of AgNO3 may not be given [29], and indeed, as already mentioned above, the C8-linker conjugated nucleoside derivative 7 (Scheme 1) shows the opposite behavior: the 3’-O

Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination

• Maëva-Charlotte Kervarec,
• Thomas Braun,
• Mike Ahrens and
• Erhard Kemnitz

Beilstein J. Org. Chem. 2020, 16, 2623–2635, doi:10.3762/bjoc.16.213

• doped with chlorine atoms which causes a distortion of the structure resulting in the amorphicity and high Lewis acidity of the compound. The reactivity of ACF towards C–F bond activations was deeply investigated. For instance, the activation of fluoromethanes was observed at ACF in the presence of

• been found in a homogeneous phase, but germylium ions can promote such reaction pathways [58]. Nevertheless, the formation of the compounds 1, 10b, 11, and 12 can alternatively be initiated by the Lewis acidity of ACF itself, as outlined above without the presence of silane (see Scheme 3). Therefore

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• , unitless), acidity-basicity potential (ABP, unitless), bioconcentration potential (BCP, unitless), persistence potential (PER, unitless), soil sorption coefficient (soil, Koc), half-life of solvent in environment (half-life, h), aquatic toxicity to fish (aqua, mg/L for 96 h), Q-phrase potential (Q-phrase

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• 9d,e. Thus, the presence of the electron-withdrawing 4-fluoroalkyl group in pyrimidones 1 is a significant structural factor playing a major role in the overall success of the Chan–Evans–Lam reaction, most likely due to related increase in NH-acidity of the heterocyclic system. The ester group and

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• literature [20][40]. The reaction of Int-1 with the alkynes 1 also gives Int-2b as a regioisomeric intermediate of Int-2a, leading to the 3-fluoroalkylated cobalt alkoxide Int-3b. Subsequently, the proton shift of the cobalt alkoxide Int-3b provides the allylcobalt species Int-4b because the acidity of the

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• ]. Firstly, in comparison to simple guanidinium cations 2 (pKa 12.5) and ammonium cations 3 (pKa 10.5), the Schmuck cation has a lower pKa value of 7 to 8 due to the increased acidity of acylguanidiniums, which favors the formation of stronger hydrogen-bonded ion pairs (Figure 1, magenta part). Secondly, the

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• -trifluoromethyl-2-thiouracil (1e) enhances the acidity of the N3H hydrogen by direct conjugation to the carbonyl moiety. As a result, 2-thiouracil 1e acts as an ambident nucleophile. Thus, the attack of the carbon atom attached to the chlorine by the N3 nitrogen atom is accompanied by the elimination of hydrogen

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• analysis and supported by HRMS. All three halogenated products were purified and isolated as a mixture (≈61% determined by NMR). The contrasting result observed with HBr/AcOH and TBAB/CSA highlighted the importance of the acidity of the medium on the reaction course of the ring-opening reaction (Scheme 5

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• this weakens their interaction. Similar considerations can be applied to the acidity of the carboxylic group (Figure 6B), where the mutual orientation of the C–X dipole and the carboxylate -CO2− charge has an effect [74]. In diastereomeric fluoroprolines there is a large difference in the mutual

• orientation of the groups, while in the (trifluoromethyl)prolines the orientation is similar. This is reflected in the acidity values. Lipophilicity Another parameter, which may be sensitive to the orientation of the dipoles within a molecule is the lipophilicity. It is well known that single aliphatic

• conformation of the side chains. The positive end of the ammonium dipole is on the hydrogen atoms attached to the nitrogen. The nitrogen atom is the negative end. B) The acidity of the carboxylic group depends on the relative orientation of the substituent dipole with respect to the charged carboxylate. Only

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• alkane products could be controlled by adjusting the acidity of the reaction media. As in the previously described examples, molecular oxygen plays a key role in the mechanism of the C–H functionalization (Figure 10). Indeed, both the photoexcited Ir-based catalyst and the superoxide radicals formed in

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• )cellulose such as the acidity, the crystallinity and the particle size of cellulose as well as the nature of the feedstocks. This review highlights all these parameters and all the strategies employed to produce isosorbide from (ligno)cellulose in a one-pot process. Keywords: catalysis; cellulose

• acid or a metal on an acid support. Here, we will report all these strategies to perform the one-pot conversion of (ligno)cellulose to isosorbide and the key parameters of this reaction (acidity, nature of the feedstocks, poisoning of the catalyst). Review Combination of an acidic homogeneous catalyst

• conversion of cellulose. If the Ru/C catalyst was associated with H2SO4 only 14% of isosorbide was produced under similar conditions. This study showed that the nature of the mineral acid and thus the acidity is of importance to produce isosorbide from cellulose. The most active metal catalyst is Ru/C among