Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• . Moreover, the nucleophilicity of the hexafluoroacetylcetonate anion is also insufficient for the substitution of chlorine atoms at the o-quinone backbone. In the case of the reaction of 4 with acetylacetone gem-dithiolate 5d the tentative mechanism of the formation of thiete species 7 is depicted in Scheme

•  2. The high extent of enolization of 1,3-diketones results in lower nucleophilicity of the active methylene function. This fact enhances the reversibility of the dithiocarboxylation of sodium acetylacetonate. It is known that dithiocarboxylates and gem-dithiolates can lose CS2 resulting in active

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• avoids pre-functionalization of the substrate, has been hindered by the lack of suitable reagents. In recent years, however, a selection of mostly electrophilic and radical sources has been introduced [27]. Nucleophilic perfluoroalkylthiolation is especially challenging due to the low nucleophilicity of

• nucleophilicity of −SRF anions [39]. Herein, we report the successful synthesis of several BT-SRF reagents and provide insights into the reactivity of different perfluoroalkylthiolate anions in nucleophilic substitution reactions. This study led to the development of unprecedented deoxygenative pentafluoroethyl

• increased prevalence of the β-fluoride elimination pathway with longer perfluoroalkylthio chains likely reflects the lower nucleophilicity of the increasingly fluorinated thiolate anions. Moreover, (perfluoroisopropyl) thioether 11a was produced in only trace amounts in the reaction with BT-SCF(CF3)2, which

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• group in 12 attenuates the nucleophilicity of the molecule, rendering the attack on the relatively bulky phosphorylated nitronate 2 inefficient. To prove this, we decided to moderate the basicity of the amine function by protection with a sulfonyl group. Gratifyingly, the N-tosylamine 17 [48] reacted

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• triflate followed by exposure to a fluorine nucleophile [31]. We selected Et3N·3HF as a simple, stable, and versatile nucleophilic reagent since it would be possible to modulate the nucleophilicity/basicity with addition of Et3N [32]. Triflate 13 [19] was engaged as a good substrate model since the product

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• show excellent nucleophilicity arising from the oxindole–hydroxyindole tautomerization [18][19], this synthetic approach is undoubtedly attractive because it could complement our previous one using nucleophilic amido-functionalized allyl boronates in terms of the structural diversity as well as

• sodium hydride, affording the corresponding adduct in 50% and 81% yields, respectively (Table 1, entries 6 and 7). Surprisingly, the desired allylation underwent even in the absence of palladium catalyst, probably due to high nucleophilicity of the deprotonated intermediate, to give 3b in 87% yield

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• reaction of adenines 5 and 6 may reflect a significantly higher nucleophilicity of the nitrogen atom of the imidazole ring versus that of the NH2 group. It should be pointed out that the mechanism depicted in Scheme 6 is highly speculative since the nature of the last step (the conversion of intermediate C

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• acids or their esters IV with o-aminothiophenol (1a) to afford the target BTAs III can be explained both by the impossibility of thioesterification/thiotransesterification to proceed under additives-free conditions and by the high nucleophilicity of the o-aminothiophenol’s SH group that attacked the

• intermediate XI intramolecularly attacked at the amide carbonyl group (Scheme 8). Such a change in the intramolecular cyclization direction, possibly, was due to the electron-withdrawing effect of the chloro-substituent in the o-aminothiophenol moiety, which decreased the nucleophilicity of the SH group

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

• most N-alkylureas III (see Figure 1a, method A) [30], led to a complex mixture of products (unpublished data), which may be attributed to the decreased nucleophilicity of the nitrogen atom bound to the aryl group. On the other hand, a previously developed synthetic non-trivial method involving the

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• basicity of the pyridine (Figure 1). In the trans configuration intramolecular coordination is prohibited and nucleophilicity and basicity are restored. Reversible switching between the two states is achieved by irradiation with green (trans→cis) and violet (cis→trans) light. The title compound of this

• photodissociable ligands. These ligands coordinate in their trans form and decoordinate in the cis configuration driven by steric hindrance [14][34][35]. Basicity and nucleophilicity switching of the 4-(N,N-dimethylamino)pyridine “record player” molecule 1. Composition of the different states of porphyrin 1 (1 mM

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• electrophilic radical R• together with stoichiometric bromide ion; R• subsequently adds to the β-carbon of the allenamide 15, providing an α-aminoallyl radical 41. To support this hypothesis the calculated HOMO of allenamide 15 is shown in Scheme 5b, signifying the increased nucleophilicity at the β-carbon [54

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• center. This in turn led to their increased nucleophilicity as compared to the standard Ugi adducts. As such, the stereocenter at the peptidyl position could be installed and stereodefined through the reaction with a suitable electrophile. Towards this end, we were able to deploy an asymmetric cinchona

• research, we have been involved in the synthesis and utilization of 2-oxo-aldehyde-derived Ugi adducts 8 (Scheme 1). These products possess an increased nucleophilicity of the peptidyl position compared to the standard Ugi adducts owing to an additional electron-withdrawing group introduced with the 2-oxo

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

• -phosphonylated thiazolopyrimidine can be explained by the electron-withdrawing effect of the trifluoromethyl group in the starting 2-thiouracil. In contrast to 6-methyl- or 6-phenyl-2-thiouracil, where the nucleophilicity is localized on the sulfur atom, the presence of the electron-withdrawing CF3 group in 6

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• favorable due to the high nucleophilicity of the exocyclic amino function attached to the electron-rich tetrazole ring [45]. In support of this assumption we stopped the reaction after 4 minutes of heating under microwave irradiation and inspected the prior formation of 9 via comparison with an authentic

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• the β-disaccharide 16 (Scheme 2). A ring-opening reaction followed by subsequent glycosylation of 19 with orthogonally protected thioglucoside 10 gave trisaccharide 21 in moderate yield. To improve the yield, the nucleophilicity of the disaccharide acceptor 19 (Scheme 2) was altered by replacing the

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• allyldimethylamine (pKa 8.72), respectively [44]. This effect was reinforced by the higher nucleophilicity of the nitrogen atom in 12 compared with Et3N, as we deduced by comparison of model tertiary amines: Me3N (in MeCN: N 23.05, sN 0.45) and Et3N (in MeCN: N 17.10, sN 0.52) [45][46]. On the other hand, the lower

• nucleophilicity of pyridine compared with the tertiary alkylamine present in compound 12 [45][46] may be responsible for the lower vulnerability of 9 towards alkylation. Another approach to circumvent the formation of N-alkylation products was based on the use of the more sterically hindered diisopropyl

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• functionalized thietanes, electron-deficient sulfur ylides were investigated in the ring expansion of thiiranes. However, the reactions failed due to the poor nucleophilicity of the electron-deficient sulfur ylides. However, in the presence of rhodium catalysts, the electron-deficient sulfur ylides were

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• Knochel–Hauser base (TMPMgCl⋅LiCl), are also useful reagents for selective deprotonations due to their strong basicity and low nucleophilicity [47][48]. Knochel-type alkoxides [49], e.g., the 2-methyl-2-propoxymagnesium chloride–lithium chloride complex (tert-AmylOMgCl⋅LiCl), are less common in synthesis

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• containing electron-donating substituents; electron-poor arylboronic acids proved to be slightly less effective, probably because of their lower nucleophilicity that could have affected the transmetalation step. Moreover, we screened the reaction of a number of aromatic boronic acids 3a–j with a set of N

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• photopolymerization of epoxides [65]. Though [Al(O-t-C4F9)4]− possesses the lowest nucleophilicity in this series, its high molecular weight requires a higher loading to obtain similar OD compared with sensitizers carrying anions with lower molecular weight. There exists still the issue regarding HF formation in the

• . The nitrogens in the cyanine chain still exhibit low nucleophilicity since electron density distributes over the entire methine chain. Thus, protonation of the nitrogen in the cyanine moiety occurs with less efficiency compared to amines [117]. This strategy helped to enable cationic

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• of the corresponding tetrahydro-1,3-oxazepines. This unexpected reaction path is reasonable considering the relative ease of formation of five-membered rings as compared to the isomeric seven-membered heterocycles together with the relatively poor nucleophilicity of the carboxamide oxygen. An

• energy associated to the formation of a seven-membered heterocycle would favour the competitive ring closure leading to the five-membered ring (Scheme 2, reaction a), which would involve attack of the carboxamide nitrogen to the ω-carbon. On the other hand, the higher nucleophilicity of the sulfur in the

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• clearly showed that the NHAc group in position C-5 and the OH-4 group were oriented in a trans-diaxial configuration (Figure 2a). This enhanced the nucleophilicity of the OH-4 group due to the absence of hydrogen bonding between these moieties. After confirming the structure of 4 by single crystal X-ray

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• upon heating at reflux for 2–4 h (Table 5). The facility of thiohydantoins 5 formation could be explained by the electron-donating effect of the butyl substituents, which increased the nucleophilicity of the butyl-substituted nitrogen atoms and promoted its attack on the electrophilic center C-3a of

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

• dienophiles (Scheme 5a), whereas pentafulvenes substituted with EDG (e.g., NMe2) at the exocyclic C6 position possess an increased electron density about the fulvene π-system, increasing the stability and hence nucleophilicity of the fulvene [29][73][96][97][98][99][100][101][102][103][104]. This allows the

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• fluorosulfonyl amides 2 with nucleophilicity may attract significant attention for further applications. As depicted in Scheme 4, a plausible reaction mechanism is proposed for SO2F2-mediated transformation of amides to N-fluorosulfonyl amides. The reaction was initiated by the deprotonation of amide 1 with the

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165