A tribute to Carsten Schmuck

• Jochen Niemeyer,
• Ivo Piantanida and
• Thomas Schrader

Beilstein J. Org. Chem. 2021, 17, 2795–2798, doi:10.3762/bjoc.17.190

• , we agreed to try Carsten’s guanidiniocarbonylpyrrole (GCP) cation system in our group for DNA/RNA recognition. In that way, we started our collaboration and exchange of students which was, thanks to Carsten’s great personality, very pleasant and friendly. Moreover, due to Carsten’s profound knowledge

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of them (pathway a) includes the formation of the nitrene cation 11 [41][42][44][45][53] under action of PIFA as an oxidant. A subsequent electrophilic attack at the double bond provides aziridinium cation 12 that undergoes selective ring opening with the trifluoroacetate anion to give intermediate

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• TPC2 cation channels and the tumor cell line VCR-R CEM, and did not exhibit P-glycoprotein blocking activity. But due to their free phenolic groups they can serve as valuable intermediates for novel derivatives addressing all of these targets, based on previous evidence for structure–activity

• , antitumor, and antiviral effects [15]. Mechanistically, they have been shown to block two pore channel 2 (TPC2), an endolysosomal cation channel which is important for cellular migration and survival [6][15][46][47]. In our recent search for TPC2 blockers with antiproliferative potential we identified ring

• for effects on cation channels and the VCR-R CEM tumor cell line. As expected, the ten alkaloids did not block the cation channel TPC2, and this result confirms former evidence on structure–activity relationships on this target. In line with that, testing for biological activities of the novel

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• ] discovered the photoinduced, copper-catalyzed cyanofluoroalkylation of alkenes and fluoroalkyl iodides 12. The reaction was initiated by the reduction of CuII with tertiary amines, which formed CuICN and an amine radical cation [55]. Under irradiation by ultraviolet light, CuICN was excited and transformed

• cation I and a CuI species. This process regenerated CuII in the presence of molecular oxygen. The deprotonation of the nitrogen radical cation produces an α–amino radical II, which was further oxidized to the iminium ion III to which the copper alkynylide added forming the desired product (Scheme 17

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

• pyridinium cation intermediate A. The in situ generated tert-butoxide anion has enough basicity to deprotonate of the activated benzylic proton of intermediate A and generates the anion B1, which can be tautomerized into more stable enamine intermediate B2. Finally, the intermediates B1 or B2 occur an

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• (GFPP, C25) for sesterterpene biosynthesis. Type I terpene synthases (TPSs) activate these acyclic molecules by the abstraction of diphosphate to produce a reactive allyl cation that can initiate a cascade reaction through typical carbocation chemistry, including cyclisation reactions by intramolecular

• overall structures are very similar and constitute an α-helical fold that was first described for the FPP synthase (FPPS) from chicken (Gallus gallus) [10]. A helix G break first observed in tobacco 5-epi-aristolochene synthase with a nearby main chain carbonyl group stabilises the allyl cation of the

• , CHCl3) [13]) revealed that this product was nearly a racemate. This unexpected finding is explainable by two different cyclisation modes of GGPP to the (R)- and the (S)-cembranyl cation (A, Scheme 1). The cationic centre of (R)-A may be in close proximity to an active site water, which may be able to

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

• cyclization of secondary and tertiary l-alkynyl-2,3-epoxyalcohols 131a [94]. This is an example of a Hg(II)-salt-catalyzed rearrangement of 1-alkynyl-2,3-epoxy alcohols to substituted furans. The furan 133a was formed by dehydration of intermediate 132a through the corresponding oxonium cation. When R3 is an

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• synthesis of trisphaeridine to afford the product in four linear steps in an overall yield of 6.5% from 1-bromo-2,4,5-trimethoxybenzene. Keywords: aromatic compounds; cyclization; iminyl radical; phenanthridines; radical cation; synthesis; UV irradiation; Introduction Phenanthridine derivatives have

• . Once intermediate 18b is formed an H+ is abstracted by an acetate ion from the methoxy substituent again forming formaldehyde and acetic acid, along with subsequent quenching of the cation to restore aromaticity. Examples of photoredox-catalyzed cation radical accelerated reactions with the aromatic

• having a methoxy substituent as the leaving group for the formation of phenanthridines. Structure–reactivity relationship studies also indicated that an ortho- or para-methoxy group must be present to stabilize the incipient radical or radical cation intermediate. We propose that the reaction is

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• on our findings. The authors reported the arylation of different substrates by irradiating aryldiazonium salts in methanol with blue light in the absence of a catalyst. Radicals are proclaimed to be generated through excitation of an intermediate aryl cation formed in the reaction. Eager to

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• solvent-separated or solvent-shared ion pairs – in which the components have their own solvent shells –, nonpolar solvents are more likely to lead to contact-ion pairs. As such, the cation and anion are in closer proximity as one solvent shell is shared. If a chiral catalyst binds then to the anion, a

• anion-binding catalysis has been successfully demonstrated for other halogens, and different types of substrates such as the benzhydryl cation [48][49][50][51]. Halides as counter-anions vs nucleophiles The latest advances in anion-binding catalysis not only allowed for excellent translation of

• the seleniranium ring. Through favorable cation–π interactions with the catalyst, the (S,S)-intermediate reacts faster than its opposing enantiomer, allowing for excellent yields up to 95% and high enantioselectivities up to 91% ee. In contrast to the previous example, in which the chloride anion was

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• a fused seven- and five-membered ring [1][2][3][4][5]. The electron drift from the seven-membered ring to the five-membered ring is responsible for its polarized structure which features both a 6 π electron tropylium cation and a 6 π electron cyclopentadienyl anion in the same molecule (Figure 1

• better stabilization of cation radicals, di-, and polycations by the unique dipolar nature of azulene, and in the case of iodine doping, it was attributed to the strengthened spin–spin interaction arising due to a high radical concentration. Recently, it was also established that the water-dispersible

• here as it is polar resonance stabilized and protonation leads to a drift in its electron density from the seven-membered ring to the five-membered ring generating a stable tropylium cation making it a strong electron acceptor during the intramolecular charge transfer (ICT) process. These protonated

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• , 11 of them were never synthesized before. Markedly, noncharged structures, negatively charged cyanine bearing Na+ as counter cation, and positively charged cyanines bearing (B(Ph)4−) or (I−) as counter anions were examined as promising NIR light photoinitiating systems. Excellent photoinitiating

• mild irradiation conditions (much longer wavelength than UV light). As shown in the Scheme 1, the dyes investigated in this work differ by the counter anion and cation, respectively. By taking into account the effect of the counter ion, the trend in efficiency follows the order BPh4– > I– > Na+. The

• as an electron-donating component with the radical cation dye•+ and therefore, the dye/borate system is able to generate additional free radicals in the reaction medium, improving, in turn, the polymerization process (Scheme 7). This behavior has already been reported in the literature and is in full

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• cation chelation via the N-2 atom electron lone pair and the C-3 substituent X=O functionality, respectively [24]. Tight ion pair formation with the sodium cation and both the N-2 atom and C-3 substituents of the indazole scaffold likely hinders the approach of the electrophile to N-2 and directs

• cation, N-2 atom, and chelating X=O C-3 group of the indazole ring predominates. Although the C-3 methyl carboxylate group of 9 may contribute to selective N-1 alkylation through steric effects, the use of DMF as the reaction solvent does not support tight ion pair formation and diminishes N-1

• regioselectivity. Further variation of the alkali metal cation, through the use of strong hydride bases, such as LiH or KH in THF, to examine N-1 regioselectivity (Table 3, entries 5 and 6, respectively) revealed a high preference for the formation of N-1 regioisomer 10 (ratio N-1 (10):N:2 (11) = 28:1 and 11:1

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

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

• formed by the conjugate addition of the phosphine to the Michael acceptor, is believed to be protonated by the alcohol forming the actual catalytically active species namely ion pair ii, consisting of a phosphonium cation and an alkoxide. The alkoxide in ii then reacts with another electrophile

• 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

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

• those with less activated phenyl unities. However, electron-withdrawing groups were not suitable substrates for this reaction, most probably because of the lower stability of the cyclohexadienyl cation intermediate formed (see Scheme 31, intermediate D). A replacement of the phenyl moiety with N

• reaction rate-determining step in a radical mechanism in which the alkane participates in both the initiation and propagation steps of the radical chain (Scheme 37C). Photoinduced electron transfer Under photoinduced electron transfer (PET) conditions, olefins generate cation radical species that are

• useful intermediates in polyene cyclization cascades [78][120]. Usually, the cation formed (see Scheme 38B) is trapped in an anti-Markovnikov fashion by a nucleophile, such as water or alcohol, present in the medium, while the radical engages in the cyclization cascade. Interestingly, in 2015, Luo

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

• , protonation might not be the key step, and the highly oxidizing nature of nitration conditions that can lead to the formation of a cationic intermediate via a radical cation might control this reaction [68]. A possible mechanism for the formation of 5 and 6 starts with protonation of 1 give the Wheland

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• of the first substrate gave a mixture of but-1-ene and but-3-en-1-ol, in accordance with the loss of the C-4 alkyl group as a radical, since the formation of a cylopropylmethyl cation would have generated a mixture of cyclobutanol and cyclopropylmethanol. The second substrate gave a mixture of

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• two scenarios. The synthesis of ‘hydrophobic hydrogel’ is reported and its application in delayed cation delivery was investigated. Furthermore, pores of the initial hydrogel were modified by the formation of a secondary polymer network. Such a facile and straightforward synthetic protocol to

• physical adsorption/releasing performance being under the control of intermolecular interactions. Hydrophobization might enhance the hydrophobic interactions between the dye core and the polymer network, thus releasing can be achieved in a longer term. As a last simulative experiment, cation (K+, Ca2+, Mg2

• +) releasing performances of HGCM and HGCM-vTA after an overnight immersion in separately prepared stock solutions were analysed via ICP-OES (Supporting Information File 1, Figure S4b). HGCM shows higher cation releasing which might be driven by osmosis, however, HGCM-vTA retains cations thus offering a slower

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• state, the metal cation of the enolate is being coordinated with both nitrogen and oxygen atoms of the sulfinimine [25][26] (Scheme 3). In 1999, Ellman and co-workers described the reduction of sulfinyl imines using sodium borohydride (NaBH4) [34] or o ʟ-selectride [35]. Davis–Ellman transition state

• crystallographic analysis, and it was found that the configuration of the newly generated stereocenter was R. Huang and co-workers proposed a cyclic transition state determined by the coordination of the nitrogen of the imine, and the oxygen atoms of the sulfoxonium and sulfinyl units to the sodium cation, which

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• coordination of ZnI2. When the α-anomer of thioglycoside 17 was separately subjected to the reaction conditions, the byproduct 20 started to form in trace amounts in accordance with the suggested mechanism. The ring contraction may involve formation of a transient oxiranium cation as suggested in Scheme 2 [42

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

• heating for the synthesis of a series of alkyl- and arylbiguanides to study the drug uptake of biguanide derivatives by organic cation transporters OCT1 and OCT2. The reaction conditions involved refluxing acetonitrile overnight with 1.5 equivalents of TMSCl, resulting in the desired products in variable