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

• terminal alkynes has been achieved in a continuous-flow microreactor through 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/copper relay catalysis. The reaction is easily scalable and requires low concentration of supporting electrolyte and no external chemical oxidants or ligands, providing straightforward

• electrocatalytic dehydrogenative cross-coupling reaction of tetrahydroisoquinolines with terminal alkynes in continuous flow (Scheme 1D). These reactions require low loadings of supporting electrolyte and proceed through Cu/TEMPO relay catalysis without need for additional ligands. Results and Discussion The

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• solubilizers, bile acids are now recognized as metabolism regulators through specific receptors: farnesoid X receptor (FXR) and Takeda G protein receptor 5 (TGR5) [1][2][3]. Research efforts to find ligands for these receptors initiated several synthetic studies where bile acids are being used as a starting

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• catalyst in the presence of a substrate possessing a prochiral migrating group or (2) stereospecifically by means of a chiral α-ketol. As an example of an enantioselective rearrangement, complexes of nickel(II) with a series of chiral 1,2-diaminopropane or pyridineoxazoline ligands were evaluated for their

• with greater than 80% ee. As a third example of an enantioselective α-ketol rearrangement, Dai et al. used a chiral Al(III) catalyst to induce the rearrangement of 3 (Ar = Ph) and several aryl derivatives 9 (Figure 4) [6]. Among the N,N′-dioxide ligands explored, 11, which was derived from ʟ

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• alter cryogel pore size and mechanical properties. In addition, Tam et al. demonstrated the optical transparency with three-dimensional spatial control of immobilised bioactive growth factors using multiphoton patterning and cellular response to immobilised ligands as shown in Figure 6 [94]. Researchers

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

• cooperative steric hindrance based on bulky substituents at the 2,9-position of the phenanthroline moiety [32][33]. Alternatively, heteroleptic CuI complexes with phenanthroline and bulky chelating phosphine ligands were also synthesized [30][34][35]. The photophysical properties are dramatically modified by

• requirements of a given photochemical process. The different ligands and CuI complexes are shown in Scheme 3 [21][30]. The catalysis mechanisms of these CuI complexes are discussed in the following sections. 2. Mechanisms underlying the photoredox catalysis of copper complexes The mechanisms underlying the

• photoredox catalysis of CuI complexes with different ligands were investigated by Reiser’s group [21]. Other studies have since provided more information on the photoredox mechanisms underlying the catalysis of copper complexes [37]. In general, redox-active copper complexes include CuI and CuII complexes

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

• vinylindoline derivatives 125 was achieved by utilizing chiral ligands like chiral binaphane (Scheme 37) [91]. They had observed that the formation of six- and seven-membered rings required elevated temperatures. Subsequently, the same group studied the cyclization of arylene 126 to furnish naphthalene

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

• , resulting in a multitude of applications in dyes [11], molecular electronics [12], and oxidants or ligands in organic chemistry [13][14]. This wide range of applications has long fueled an interest in exploring innovative ways of functionalizing quinones. However, arylation of (benzo)quinones has proven to

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

• increase activity [11][12]. These nanoparticles have been decorated with targeting ligands to enhance the accumulation of the drug in cancer tissue. The activity of arsenic drugs could, however, also be enhanced by targeting mitochondria inside the cells, the target of action of arsenic drugs. To the

• efficiency. Micelles are ideal carriers when designing a nanoparticle with an abundance of functional groups on the surface, which could be conjugated with targeting ligands such as TPP. Moreover, they have already been used to successfully deliver arsenic drugs [28][29][30][31][32], highlighting their

• explore if the attachment of mitochondria targeting ligands can enhance the activity of PENAO using the nanoparticles that were recently described in our group [28][42]. Results and Discussion Synthesis of Micelles by PISA Initially two nanoparticles were prepared that had comparable particle sizes, which

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• (preQ1) [1]. Thus far, present-day riboswitches have only been known to bind – but not to be able to react – with their ligands [2][3]. This new finding now opens exciting avenues for the development of RNA labeling tools [4], in particular, for RNA methylation, and more generally, for RNA alkylation. To

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