Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• catalysis (Scheme 17) [71]. The reaction relied on the chiral biimidazoline ligand 30, which gave the best results among various tested chiral bioxazolines and chiral biimidazoline ligands. Notably, the aryl substituent at the imidazoline nitrogen of the ligands significantly affected the product yields and

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

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• observed selectivities in metathesis reactions, H-bonding interactions between chloride ligands as H-bond acceptors and OH or NH functions in the metathesis intermediate appear to be determining [35][36]. Selectivity derived from chelation is considered to be an another important contributor. Through the

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

• have been used as additives in these reactions and are suggested to act as ligands, assist proton transfer and promote the formation of oligovanadates by decreasing the pH value of the solution. The mechanisms of some vanadium-mediated oxidation reactions of alkanes have been studied, most of them

• compounds to produce the corresponding biaryl products with high enantiopurity using vanadium chelated with chiral ligands, such as tridentate asymmetric imine ligands, have been reported. For instance, (S)-binol derivatives could be successfully prepared from 2-naphthols using a dimeric vanadium complex

• -rich ligands along with the addition of Brønsted and Lewis acids, such as acetic acid and LiCl, was suggested to account for the suitability of the method for the coupling of oxidatively resistant substrates. The usefulness of this method was demonstrated in the preparation of the bicarbazole moiety

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

• . The efficiency of the solvent radical cage in maintaining the geminate radical pair could be modulated by stereoelectronic changes in the ligands of the transition-metal complexes to favor a desired pathway. One reaction particularity that was sensible to the solvent cage efficiency was the

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• etomidate [4] and the antileukemia agent nilotinib [5]. The outstanding and diverse bioactivity of imidazole-containing pharmaceuticals [6], as well as their role as ligands for transition metals [7], and organocatalysis [8], has stimulated an array of creative syntheses [9][10]. Among the numerous routes

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

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• , overall crystal packing is more reliant on the substituent groups and axial ligands. A final point in this series is the large increase in distortion comparing 5,10-di-halo-substituted (16) to 5,15-di-halo-substituted (9) derivatives due to the ‘trans’ nature of the substituents. Other halogeno

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

• ligands [52][53][54][55] and as chiral auxiliaries [56]. The most widely used synthetic methods to form the aziridine ring [57][58][59][60][61] include intramolecular cyclizations in amines bearing potential leaving groups. Stereoselective syntheses of aziridines have been successfully carried out by

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

• (phosphines, NHC-carbenes, bisoxazolines, pyridine-oxazolines, and miscellaneous) is used. Review Catalytic systems based on phosphine ligands A pioneering work on the enantioselective addition of boron-derived carbon nucleophiles to cyclic enones was published by the group of Miyaura et al. in 2005 [32

• -hydride elimination. However, the obtained yields were inconsistent. The usage of Pd(TFA)2 led to a better reproducibility of the results. From the various diphosphine ligands tested, (R,R)-MeDuPhos (L2) was identified as the one leading to the best level of enantioselectivity (up to 99% yield and up to

• the reaction (Scheme 6) [40]. A different approach using microwave irradiation was explored by the group of Toma et al. [41]. After an initial tuning of the reaction conditions of a catalytic system based on Pd(OAc)2/2,2’-bipy several optically pure phosphoramidite and diphosphine ligands in

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

• chemical function, which has attracted much attention a century ago and is showing resurgent interest in recent years after a long period of dormancy. This class of compounds has found broad applications such as reaction catalysts, organic strong bases, ligands for metal complexation, or versatile starting

• standard disinfectant and antiseptic. Although scarcely represented, the number of “success stories” with biguanide-containing compounds highlights their value and their unexploited potential as future drugs in various therapeutic fields or as efficient metal ligands. This review provides an extensive and

• : amidine; biguanide; guanidine chemistry; metformin derivatives; polynitrogen ligands; synthetic methodology; Introduction Biguanide – or amidinoguanidine – is a chemical compound derived from guanidine in which two guanidine molecules are linked through a common nitrogen atom. Since its first synthesis

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

• , specifically 13- and 9-substituted berberine derivatives have gained much interest as selective DNA ligands that specifically target quadruplex DNA (G4-DNA) [23][24][25][26][27][28][29], i.e., non-canonical, biologically relevant DNA structures that are formed by the association of four guanine-rich DNA

• forms, the effect of thermally induced unfolding of dye-labeled, quadruplex-forming oligonucleotides in the presence of the ligands was studied. In general, the binding of the ligand to the G4-DNA leads to a stabilization and thus to an increasing melting temperature of the DNA (Table 2). This effect of

• the ligands on the quadruplex melting temperature, Tm, of the labeled G4-DNA F21T [fluo-G3(TTAG3)3-tamra; fluo = fluorescein, tamra = tetramethylrhodamine], Fa2T [fluo-(ACAG3TGT)2-tamra], FmycT [fluo-TGAG3TG3TAG3TG3TA-tamra] and FkitT [fluo-AG3AG3CGCTG3AG2AG3-tamra] was determined by fluorimetric

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

• [9] and ligands [10], one can modulate the biodistribution of the LNP in the body. However, despite these advances, targeting of LNPs to the brain tissue remains a challenge [11]. In order to reach safer therapeutic options for treatment of brain diseases and disorders, a productive drug transport

• of LNPs through the notoriously protective BBB is to use short positively charged peptides or receptor-specific ligands, both of which have shown to be effective at increasing transport of LNPs, nucleotides, and small molecules through the BBB [9][15][16][17]. For example, the short positively

• ]. The HIV-1 Tat protein itself has been shown to traverse the BBB by acting as a cell-penetrating peptide [9][20]. Other small positively charged molecules used for BBB penetration include transferrin and corresponding peptide derivatives or analogs that act as ligands for the transferrin receptor. The

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• compounds in catalytic technologies, biochemistry, and materials [1][2][3][4][5][6]. In particular, in coordination chemistry and catalyst chemistry, organophosphorus compounds such as triorganylphosphines are widely used as typical monodentate ligands for many metals [7][8]. In addition, diphosphines such

• as 1,2-bis(diphenylphosphino)ethane (Ph2PCH2CH2PPh2, dppe) are employed as bidentate ligands and are effective in controlling important catalytic reactions such as cross-coupling reactions [9][10][11][12][13][14][15][16][17][18]. 1,2-Bis(diphenylphosphino)ethylene (Ph2PCH=CHPPh2, dppen) is among

• bidentate diphosphine ligands having a rigid structure and has increased attention as a useful and effective ligand in coordinating with various metals [19][20]. (Z)-Ph2PCH=CHPPh2 is very important as a bidentate ligand for many mononuclear complexes [21][22][23]. On the other hand, (E)-Ph2PCH=CHPPh2 acts

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

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• potential large-scale preparations. Thioamides are highly attractive molecules in pharmaceuticals, agrochemicals, electronic chemicals, and materials sciences [17][18][19][20][21][22][23][24][25][26][27]. In coordination chemistry, pincer-type ligands containing a thioamide motif were shown to exhibit

• simplify the work-up of the reaction with LR, this newly developed method was extended to synthesize two pincer ligands, N2,N6-di(n-butyl)pyridine-2,6-bis(carbothioamide) (4, Scheme 1) and N2,N6-bis(2,4,6-trimethylphenyl)pyridine-2,6-bis(carbothioamide) (6, Scheme 2) [34][35][43][44]. With a slight excess

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• utilized as building blocks for more demanding ligands and catalysts became a task of high importance. Thus, several strategies to access enantioenriched [2.2]paracyclophanes have been reported, either relying on classical resolution approaches or, more recently, making use of asymmetric catalysis to carry

• decades, it was shown that enantioenriched 2 may serve as a valuable building block to access more advanced chiral cyclophane ligands and catalysts [3][4][19][20][21][22] and therefore its asymmetric synthesis became an important task [3][4][18][19][20][21][22][23][24][25][26][27]. Several strategies to

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , these diazo compounds undergo [3 + 2] cycloadditions with suitable substrates to render various nitrogen-rich heterocycles [39]. In addition to their synthetic importance, these are frequently encountered as ligands in many metal complexes [40][41][42][43]. Our group have also employed 1,3-dicarbonyl

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• of 1,2,4-triazolobenzodiazepines is the treatment of central nervous system (CNS) disorders. Such drugs as alprazolam and estazolam are used as anxiolytic agents, whereas adinazolam is known as an antidepressant [3]. Benzodiazepine molecules are ligands for GABA-receptors and act as positive

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• pincer ligands 57, 58 [102], 59 [103], and 60 [104], or the so-called “bucky ligands” (Scheme 18). In the development of new organometallic C60 compounds that can be used as homogeneous catalysts, new blocks 61 and 62, cross-conjugated through cyclopropane, were synthesized (Scheme 19) [104]. Attaching

• such an electron-enriched metal-containing system to C60 can result in push–pull blocks with new electronic and photochemical properties, as demonstrated by complexes 63, 64 [103], and 65 [104] in Figure 6. The syntheses of new types of N-containing fullerene ligands for metal complexes 66–68 are

• nitrophenylfullerenes 48 and 50. Synthesis of conjugate 52 of C60 with ethyl diazo(4-nitrophenyl)acetate. Synthesis of fluoride-containing phenylmethanofullerenes 53–56. Synthesis of “bucky ligands” 57–60. The synthetic route to methanofullerene-based palladium–bisaminoaryl complex 62. Synthesis of N-containing

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

• temperature (35 °C) but toxic CH2Cl2 solvent (Scheme 1). The reaction using second-generation N-heterocyclic carbene ligands was faster and preferably yielded cyclododecatriene. Larger cyclic butadienes may be used in the production of flame retardants, lubricants and specialty polymers [149][150]. 3.1.3

• the glycolytic depolymerisation of PET [128][205]. The highest BHET yield (74.7%) was achieved using zinc chloride (0.5% w/w), an EG/PET ratio of 14:1 and reflux conditions (Table 2, entry 8). The use of preformed soluble Co(II) complexes bearing bidentate phosphorus ligands (e.g., 1,2-bis

• complexes could be used as catalysts, both in PLA alcoholysis and in PLA synthesis via lactide polymerisation. Metal species other than zinc were reported as effective catalysts for PLA methanolysis. Group 4 metal complexes with salalen ligands of the formula M(ligand)(OiPr)2 (M = Ti, Zr, Hf) were used in

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• anticancer drug vatalanib [26][27][28] (Figure 1). On the other hand, aminophthalazinones can be prospective candidates as N- and O-donor ligands to form complexes with biological significant metal ions, such as copper or zinc [29]. Recently, we have demonstrated a strategy for the synthesis of phthalazinone

• need to develop new and improve the existing methods for the synthesis of aminophthalazinones is important from the point of view of their properties and pharmaceutical industry interest. In the present work, we report results of our research on the synthesis, application as ligands in complexes, and

• behavior of aminophthalazinones with Cu(II) ions To conclude the synthetic research, we looked at the potential of aminophthalazinones as polydentate ligands for the synthesis of complexes with metal ions. Examples of the use of phthalazinone and its derivatives in the synthesis of coordination compounds

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• , which involves the use of targeting ligands, such as monoclonal antibodies, antibody fragments, proteins, peptides, and other small molecules, including vitamins and carbohydrates [7][8]. The targeting ligands are coupled to the surface of the carrier to selectively target tumor cells that overexpress a

• particular cell surface receptor [7][9][10][11][12][13][14]. To this aim, ligand–lipid conjugates have been developed in research and preclinical development for liposome targeting for decades. In particular, peptide ligands offer significant advantages, including efficient synthesis routes, versatility, and

• blood circulation times by allowing them to evade immune detection. PEGs often play a key role in the design of the ligands as a spacer between the nanocarrier surface and the lipid. PEGs have, however, some shortcomings, such as a broad molecular weight distribution, large steric hindrance, and the

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• dissociation binding constant of ligands (Kd) determined from the changes in the chemical shift of the labelled nuclei within the protein. Intuitively, the largest chemical shift perturbations are expected to be seen for residues in the closest proximity to the bound ligand. An additional advantage of this

• ) and 19F nuclei in native tryptophan, and 5-FTrp-labelled bromodomain protein Brd4 against a panel of ligands (Figure 4) [34]. 1H NMR was found to be 6–20 times less responsive than fluorine with regards to chemical shift perturbations. Indeed, the high resolution observed in the fluorine spectra

• -β2AR, changes in the NMR signals monitored within different helices of the protein revealed that agonist binding primarily shifted the equilibrium towards the G protein-specific active state of helix VI. In contrast, β-arrestin-biased ligands predominantly affected the conformation of specifically