Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• authors propose the intramolecular cyclization proceeds via the nucleophilic attack of a brominated or cationic benzylic position rather than a radical cyclization. In 2021, Tang and Zhang demonstrated a similar radical annulation of unsaturated carboxylic acids with disulfides for the synthesis of γ

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• through reversible reaction with this cationic species. Conclusion In summary, we have achieved the electrochemical dehydrogenation cross-coupling of tetrahydroisoquinolines with terminal alkynes in continuous flow through Cu/TEMPO relay catalysis. This work demonstrates that continuous-flow

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• trapped by Cu(II) to deliver the Cu(III) species 12, which undergoes intramolecular annulation and reductive elimination to afford the desired product 8 and regenerate the Cu(I) catalyst. Path b: vinyl radical intermediate 11 is oxidized by Cu(II) to give the cationic vinyl species 14. Finally, the

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

• attack of an olefinic double bond to the cationic centre Wagner–Meerwein rearrangements, and proton or hydride migrations [2]. These multistep cascade reactions ultimately result in terpene hydrocarbons that are often (poly)cyclic and contain several stereogenic centres [3][4]. In some cases, water is

• incorporated by its nucleophilic attack at a cationic intermediate, leading to terpene alcohols [5][6] or sometimes ethers [7][8]. Substrate ionisation by TPSs is achieved through binding of the diphosphate portion to a trinuclear Mg2+ cluster in the active site that is itself bound to two highly conserved

• synthases seem to be quite random, only the active site is lined with mostly non-polar residues. They contour the active site and force the substrate into a certain conformation which, after substrate ionisation, determines the reaction pathway that is taken by the cationic cascade. Here we present site

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• bond of these oxadiazoles quantitatively resulted in E/Z-vinyl triflates. The reactions of the cationic intermediates have been studied by DFT calculations and the reaction mechanisms are discussed. Keywords: acetylene-oxadiazoles; Friedel–Crafts reaction; hydroarylation; superelectrophilic activation

• , as a hydride ion source, was conducted to achieve the ionic hydrogenation of intermediate cationic species. However, no products of ionic hydrogenation were obtained, only the product of the hydrophenylation of the acetylene bond 5a was quantitatively isolated (compare with data shown in Scheme 5

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

• literature. Utilization of Hg(II) salts in the intramolecular cationic cyclization of olefinic, acetylenic, and allenic substrates having aromatic rings, nucleophiles, and heteroatoms in the neighborhood were well documented. Hg(II) reagents were also often employed in the important cyclization step during

• Yamamoto et al [116]. The catalytic pathway was proved to involve the direct H-transfer to the vinylmercury complex from the aromatic ring. It involved Hg(OTf)2-catalyzed cyclization of aryl 1,1-disubstituted allenes with the formation of a quaternary carbon center followed by the formation of a cationic

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• peptides and proteins have been linked to nanotechnology. DQA and TPP are both cationic and lipophilic molecules and therefore able to easily pass the mitochondrial membrane [15][16][17][18][19]. TPP is the most-studied mitochondrial targeting agent and has shown to accumulate 1000 times more in the

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

• the cationic reactive species. Keywords: anion binding; asymmetric catalysis; halide anions; hydrogen donors; noncovalent interactions; Introduction Halogens and the respective anionic halides occupy an essential role in natural and chemical processes [1][2][3][4]. While in chemical syntheses

• anion coordination and supramolecular chemistry [7][8][9][10][11], this field of research has attracted more attention within the past two decades. Immense efforts were made to identify small molecules that are able to productively bind anions via noncovalent hydrogen bonding, from which cationic

• proton of the enolizable β-ketoester 49 and thus activating the nucleophilic species. This enolate then adds to the cationic substrate from in situ upon halide abstraction of α-chloro amino acid derivatives 48 by the thiourea moiety of the bifunctional catalyst (Scheme 10c, key intermediate), leading to

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

• , Fukutomi, and Nakayama [19] reported the synthesis of what they described as ‘true polyazulene’ through a cationic polymerization reaction. Their protocol involved heating the trifluoroacetic acid (TFA) solution of azulene (1) followed by treatment with triethylamine to obtain a brown polymeric product

• ) complexes. Synthesis of ‘true polyazulene’ 3 or 3’ by cationic polymerization. Synthesis of 1,3-polyazulene 5 by Yamamoto protocol. Synthesis of 4,7-dibromo-6-(n-alkyl)azulenes 12–14. Synthesis of (A) 4,7-diethynyl-6-(n-dodecyl)azulene (16) and (B) 4,7-polyazulene 17 containing an ethynyl spacer. Synthesis

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

• process is expected with different NIR dyes [9]. Table 1 and Figure S2 (Supporting Information File 1) clearly show the exothermicity observed upon irradiation. The proposed NIR dye/iodonium combinations are able to generate free radicals and cationic species (Scheme 7 and Figure 4), and these two

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

• . Cationic ROP of anhydrosugars was the pioneering approach for the preparation of synthetic, unnatural xylans. Polyxylofurans with (1–5) and (3–5) linkages were described [199][200]. In most cases, non-uniform polysaccharides were obtained, as in the case of α(1–5)-xylans, prepared in up to 93% yields and

• , enabling the synthesis of a 32mer [272]. The construction of α(1–6)-mannans (up to 10mer) bearing α(1–2)-Man branches was also accomplished using phosphate, N-phenyltrifluoroacetimidate or n-pentenylorthoester donors [273][274]. An approach using a (cationic) ROP method using tricyclic orthoester Man BBs

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• strategy that has been employed to optimize the delivery profile of ASOs, is the functionalization of ASOs with cationic amine groups, either by direct conjugation onto the sugar, nucleobase or internucleotide linkage. The introduction of these positively charged groups has improved properties like

• nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has

• been separated into three sections, nucleobase, sugar and backbone modifications, highlighting what impact the cationic amine groups have on the ONs/ASOs physiochemical and biological properties. Finally, a concluding section has been added, summarizing the important knowledge from the three chapters

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

• moisture, while HF seriously attacks human skin. The N-F fluorinating agents can be classified into two categories: these are neutral and cationic. This review covers the chronological advancement of these reagents regardless of their classification, as they advanced side by side. Review 1. Historical

• gave higher yields of the protonated products 4-3. 1-5. N-Fluoropyridinium salts and their derivatives In 1986, Umemoto et al. reported N-fluoropyridinium triflate and its derivatives 5-4 as new stable cationic fluorinating agents. These possessed either electron-donating or -withdrawing substituents

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

• phosphono-PNAs retained the stability against nucleases. In another study, conjugation with glutamine phosphonate or lysine bis-phosphonate amino acid derivatives introduced up to twelve negative charges (phosphonate moieties) into PNAs [91]. The negative charges allowed cationic lipid-mediated delivery of

• cationic RNA binding compounds, perhaps, because the protonation event is coupled with the Hoogsteen hydrogen bond formation. As a result, the partially protonated M strengthens the triple helix without compromising the sequence specificity of recognition [28][30][31]. As discussed above, guanidine groups

• triplex, most likely due to reduced ability of R to π-stack [103]. As expected, fluorescence microscopy showed improved cellular uptake of the cationic guanidinium-modified PNAs [103]. PNA nucleobases for Hoogsteen recognition of adenine: Because the T•A–T triplets are reasonably stable under

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

• . Cationic gold(I) complexes are also suitable catalysts for olefin functionalization, and their use has become more popular than gold(III) catalysis [39]. In 2007, Che and Zhou reported the olefin intramolecular hydroalkylation of N-alkenyl β-ketoamides 13 using the gold(I)–phosphine complex Au[P(t-Bu)2(o

• the aza-Michael addition and that only the cationic gold(I) complex was associated with the intramolecular hydroalkylation reaction. These observations justified the use of a three-fold excess of AgOCl in relation to the gold complex since the silver salt participated both as a source of a non

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

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

• in 20 mL distilled water refreshed repeatedly every 2 hours for 3 times and then left in a fume hood for drying overnight. This procedure was repeated for each substructuring monomer categorized as acidic AA (10 mol % MBA), cationic AAM (10 mol % MBA), and neutral PEGMEMA (10 mol % PEGDMA). Rhodamine

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• progresses under neutral conditions. The authors postulated that the vacancy on the square-planar Pd(II) species allows a faster alkene insertion in comparison to Pd(0). The cationic Pd(II) enolate exists as a dynamic mixture of C- and O-bound enolate and is highly susceptible to hydrolysis. This means that

• increased the catalytic activity and allowed to run the reaction at a lower temperature [48]. This can be very useful for substrates that can react with traces of Pd(0) that are formed by minor side reactions. The authors suspected that hexafluorophosphate anions stabilize the cationic Pd species and result

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

• -aryl substituent to the berberine chromophore. The latter has been shown to operate also in resembling cationic, biaryl-type dyes [42][43]. Along the same lines, the low intrinsic emission quantum yield of the parent berberine (1a) has been suggested to result from an internal charge transfer (ICT

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• challenging. In an effort to target LNPs composed of an ionizable cationic lipid (DLin-MC3-DMA), cholesterol, the phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (DMG-PEG 2000) to particular cell types, as well as to generate

• this study, we employed lipid compositions and formulation procedures previously reported in literature [4]. Specifically, the cationic and ionizable DLin-MC3-DMA lipid is a constituent of the FDA-approved LNP-formulated siRNA drug Patisiran® for treatment of familial transthyretin amyloidosis [36][37

• ]. Clinical trial safety assessments of this formulation showed no liver toxicity and no immune stimulation, with ≈10% of trial participants experiencing mild to moderate adverse events upon administration [38]. It includes encapsulation of siRNA by a mixture of lipid components, such as an ionizable cationic

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• 2, owing to the increased electron deficiency of the phosphorus center in the former. In particular, the energy levels in cationic phospholium 5 are significantly stabilized because of the cationic nature of the phosphorus center. These results are consistent with the 31P NMR observations discussed

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

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• success of our DMF-free systems lies in the generation of sterically demanding cationic species, [P4-t-Bu]H+ or glyme capsulized K+, resulting in the stabilization of CF3− from HCF3 by ion separation. The sterically demanding [P4-t-Bu]H+ or encapsulation of K+ by glymes effectively inhibits the contact of

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

• fluorine, which helps to generate cations but does not affect cationic reactions [23][24][25][26][27]. Thus, HFIP greatly facilitates reactions via cationic intermediates [28]. In the presence of a catalytic amount of trifluoromethanesulfonic acid in HFIP, (biaryl-2-yl)acetoaldehydes or their acetal