Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• derivative 4a (1 equiv) and aliphatic amine 9a (2.5 equiv) in glacial acetic acid [42] resulted in the formation of product 10aa with a yield of only 36%. It is clear that compound 9a could be protonated in the acidic environment, decreasing its nucleophilicity and therefore, product 10aa was obtained in low

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• -acyliminium ions, a proton source for which the conjugate base has no nucleophilicity would be necessary in the cathodic reduction. After several attempts, we finally reached HBF4·OEt2 as a proton source for cathodic reduction and the result is shown in entry 2 of Table 1. Strong increases of conversion of 1

• to HBF4·OEt, for which the conjugate base has no nucleophilicity, improved the yield of 2 and the conversion of 1. Incidentally, this reaction medium includes a base, iPr2NEt, that would accelerate the deprotonation step in the formation of N-acyliminium ions from DMA at the anode. TFA and HBF4·OEt2

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• salts 2 and an α-halopropiophenone. Unfortunately, initial attempts of a nucleophilic attack of sodium perfluorooctylsulfinate (2c) on α-bromopropiophenone (3) were unsuccessful to produce the desired product 1c due to the insufficient nucleophilicity of the sulfinate to substitute a bromide on a

• the molar ratio. Ranging from a 2.5:1 until a 10:1 molar ratio, yields increased significantly from 20% to 68%; however, a 5:1 ratio offered us a similar yield with a much shorter workup time when the reaction concentration was doubled. Knowing that nucleophilicity is a key factor in this reaction, we

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• excellently for most of the electron-rich anilines due to their increased nucleophilicity. A comparison of ortho-, meta- and para-substituted derivatives revealed that for electron-rich anilines, the para-substituted ABs are formed in better yields as their ortho- and meta-analogues. For example, the

• . Low yields in case of electron-poor aniline derivatives can be explained by the reduced nucleophilicity. To exemplarily demonstrate the optimization for electron-poor derivatives, the synthesis of p-cyano-substituted AB 1o was repeated at higher temperatures. Thereby the yield of 1o could be increased

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• the interaction of the lowest unoccupied molecular orbital (LUMO) of the azomethine ylide 1 with the highest occupied molecular orbital (HOMO) of cyclopropenes 2. It follows that the greater the nucleophilicity of the cyclopropene substrate 2 is, the higher is its reactivity towards the 1,3-dipole 1

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• reagents to give versatile cyclic compounds with recovery of the tertiary phosphine [25][26][27][28][29][30][31][32][33][34]. The superior catalytic ability of tertiary phosphines was primarily attributed to their excellent nucleophilicity as a nucleophile trigger and decent cleaving ability as a leaving

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• catalyst and additive. The 1H NMR-spectroscopic analysis of the reaction showed that in both attempts no reaction occurred. It may be concluded that the nucleophilicity of the boronic ester is not sufficient, however, under the employed conditions, it can be hydrolyzed to the more reactive boronic acid

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• highly nucleophilic indole C3 as the peri position, with the latter being often more nucleophilic than the former. Noteworthy is that the kinetic preference for ring-closure onto the C5 position may be a more dominating factor than the higher nucleophilicity of the C3 position (or vice versa). Due to

• substrates 20. Noteworthy is that substrates bearing an indolyl N–Ph or N–Boc moiety (instead of free indolyl N–H) failed to deliver the corresponding final cyclized products. The authors attributed this failure to the indole C3 position’s reduced nucleophilicity which thwarted the Michael addition step. In

• preference for cyclization onto the C5 position is more dominating than the higher nucleophilicity of the C3 position, making the CAr–C bond formation completely regioselective at the C5 position. Subsequently in 2017, Li and co-workers also applied the intramolecular Friedel–Crafts acylation strategy to get

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• expanded to give a two-term Equation 2 [34][36][37], where l is the sensitivity to changes in N, which is a measure of solvent nucleophilicity. The original N scale was based on the specific rates of solvolysis of methyl tosylate [38] but, with this as the standard, there is a significant problem in

• , and it was shown from studies of 1-adamantyl derivatives [36] that ionic substrates of this type solvolyze in SN1 reactions with very little variation in specific rate with changes in solvent. The solvent nucleophilicity scale developed is termed NT scale [36][37] and NT = log(k/ko)MeDBTh+; where ko

• the plot was against Y values [25][33]. Such an assignment needs to be treated with caution because the large contributions from solvent nucleophilicity effects to these solvolyses [16][17][26][27][30], even with electron-rich substrates, would be expected to lead to perturbations of plots against

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• ) × 104 M−1, which was contrary to those of hemicucurbiturils. As observed by fluorescence titration experiments, macrocycle 4 showed weak interactions with selected anions. Results and Discussion Because of the relatively strong nucleophilicity of the amino group in aniline, the synthesis could become

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• 39%, respectively), which was presumably due to their lower nucleophilicity. However, the reaction of 2a with more sterically hindered 2,6-lutidine was very sluggish and only trace amount of product 4h could be observed under the optimized conditions over 24 h. Conclusion In summary, we have

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• yield (Table 1, entries 8 and 9). However, increasing the amount of K3PO4 to 4 equivalents gave a nearly quantitative yield (Table 1, entry 12). We believe that a supplementary activation of the boronic acid, by adding a high amount of base, improved the nucleophilicity and facilitated the

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• anchimeric assistance during glycosylation (Figure 4). However, the O-2 acyl group on the glycosyl acceptor hinders the 3-O-glycosylation sterically and electronically [126]. The decreased nucleophilicity of the C-3 hydroxy acceptor could lead to poor stereoselectivity [127]. This issue becomes even more

• well as branched β(1–3)-glucans with defined lengths could be prepared by AGA [140][141][142]. The poor nucleophilicity of the C-3 hydroxy group on the glycosyl acceptor required the use of more reactive glycosyl phosphate donors and, in some cases, a double glycosylation cycle [118][143]. Longer

• solubility of β(1–3)-glucans, compared to the β(1–4) analogues, has permitted the chemical or enzymatic synthesis of long polysaccharides. Still, the poor nucleophilicity of the hydroxy group at C-3, in the presence of a C-2 ester PG, could decrease the efficiency of chemical synthesis. Hence, there is scope

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

• to an activated electrophile, e.g., an electron-deficient olefin, generating a zwitterion (i, Scheme 1). In further course, the zwitterion acts as a nucleophile or as a base [1]. The efficiency of the formation of this β-phosphonium α-carbanionic species depends on the nucleophilicity of the

• -donating groups (e.g., -CH3, -OMe, -NMe2) at the aryl moieties. In this way, the electron density on the phosphorous and thus the nucleophilicity is increased. This strategy has for example been exploited in the reaction of ethyl acrylate with 4-nitrobenzaldehyde [16], in aza-Morita–Baylis–Hillman

• aromatic rings with methoxy groups increases the pKa value from 1.31 (TPP) to 4.20 (TMTPP) (Figure 1). Methyl cation affinities (MCA) which can be used as descriptors for the nucleophilicity of a compound were calculated by Lindner et al. who suggested TMTPP (651.0 kJ/mol) to be a stronger Lewis base than

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• -carbaldehyde derivatives with electron-donating substituents in the 1-position of the indole ring system 1a–e were transformed in moderate to good yields into their corresponding γ-carboline derivatives 3aa–ac and 3ba–ea due to an enhanced C-3 nucleophilicity of the indole nucleus (Scheme 2). The formation of

• -indole-2-carbaldehyde (1h), impeded the conversion to γ-carboline 3ha (structure not shown) due to probable decomposition and decrease in nucleophilicity at the 3-position in substrate 1h. Plausible mechanism for the formation of γ-carbolines The probable mechanistic explanation (Scheme 3) for the

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• the Cu2+-catalyzed coupling reaction with the boronic acid (Scheme 2). The regioselectivity of the latter reaction step is most likely determined by a stronger nucleophilicity of the oxyanion in the 10-position of 6 that is caused by the particular electron distribution in the intermediate 6

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• the high nucleophilicity of the amino group in the substrate 23 to control the regioselectivity of the reaction (Scheme 9). 3 Indoles Indoles have a bicyclic structure consisting of a six-membered benzene ring fused with a five-membered nitrogen-containing pyrrole ring. Figure 3 depicts some of the

• -phenanthrolines and affords intermediate C. A subsequent cyclization D and aromatization E with loss of HCN yield the desired products 64. The lower yields in case of aliphatic isocyanides were reasoned with its low nucleophilicity losing the competition with aryledenemalononitrile A in the reaction with

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

• the better nucleophilicity. Indeed, a methyl lactate (Me-La) and ethyl lactate yield of 70% and 21% was obtained, respectively, using soluble zinc acetate at reflux temperature [264]. Interestingly, under the same reaction conditions, PET was unreactive, thus enabling the selectively recycle of mixed

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

• desired Eschenmoser coupling reaction (route b). Therefore, the nucleophilicity of the conjugated base of the nitrogen (benzenecarbimidothioate or thioimidate) is exerted towards the oxindole carbonyl to give the thiazole. Moreover, if both benzene rings contain electron-withdrawing groups, enhancing

• 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

• carbanion nucleophilicity and these two effects are opposing. The influence of the substituent effects, as quantified using Hammett’s substituent constants [35], on the yields can be represented graphically (Figure 2). Reaction of 1a–e with secondary thiobenzamides 3a–i Secondary thiobenzamides 3a–i also

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• -Michael addition (SMA) reactions remain a rather less explored reaction among asymmetric organocatalytic transformations, mainly because of the high nucleophilicity of thiols causing difficulties in controlling the stereoselectivity [21], despite C–S bond-forming reactions are of great interest in

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• metal catalysts. Recently, we have developed a Brønsted acid-catalyzed cycloaromatization in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as solvent [20][21][22]. Fluoroalcohols, such as HFIP, exhibit high ionization power and low nucleophilicity, based on the electron-withdrawing inductive effect of

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• thermal stability of the tetrazolium-5-aminides (see Supporting Information File 1 for more details). Some nucleophilic displacement reactions were carried out in order to show the higher reactivity of the aminides in comparison to the parent aminotetrazoles. The high nucleophilicity of the imine group in

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

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• nucleophilicity of the hydrazides diversifies the recyclization of 5-hydroxypyrrolines and results in the chemoselective formation of highly functionalized azaheterocyclic scaffolds. Such a short-cut to partially saturated azaheterocyclic scaffolds meets the interests of modern medicinal chemistry which today

• ring opening with formation of the linear intermediate C. In comparison with alkyl-, aryl-, and hetarylhydrazines [11] as well as semicarbazide and its derivatives [12], the nucleophilicity of the internal nitrogen atom of hydrazide 2 is significantly reduced. As a result, the interception of the

• formation of 1,4-dihydropyridazine 4. Conclusion In summary, an acid-catalyzed recyclization of hydroxypyrrolines (easily synthesized from ketoximes and acetylene) with hydrazides was studied. The reduced nucleophilicity of the hydrazides in comparison with other hydrazine derivatives constitutes the basis