Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• , assays that implement separation steps require RNA molecules conjugated to an affinity tag such as biotin, or any other functionality for functional selection [11][12]. Very importantly, terminal modification/functionalization is not always suitable to a specific aim. Thus, in addition to building blocks

• Sonogashira coupling following a previously established protocol [13], resulting in nucleoside derivative 7 with 44 % yield over these two steps, corresponding to an overall yield of 17% over six reaction steps. Further functionalization of 7 for RNA synthesis required selective 2’-O-silylation to deliver

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• . With this background, we proposed that the functionalization of the berberine scaffold with adenine-appended alkyl substituents may provide a useful platform to further explore this important aspect. Specifically, we wished to examine whether adenine–berberine conjugates with a varying linker length

• -forming repeat unit from the “insulin-linked polymorphic region” (ILPR) [50], that was also shown to bind quadruplex ligands [51]. Results Synthesis As the Cu-catalyzed click reaction between azides and alkynes is a well-established method for the variable functionalization of G4-DNA ligands [52], the

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• functionalization. The azido groups also can undergo a CuAAC reaction with alkynes substituted with ester functionalities, which can subsequently be hydrolyzed to either the di- or tetra acids. Using the CuAAC reaction, it was also possible to install aliphatic chains. Introducing picoline residues on the 3,6

• agitation (a), just after agitation (b), and 50 s after agitation (c). Synthesis of 5 from levoglucosan (1). Functionalization of the building block 5β. Hydrolysis of the ethyl esters 12 and 13. Synthesis of compound 19 from building block 5. Supporting Information Supporting Information File 346

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• (Scheme 9). With the aim to enable the further functionalization of the products of the oxaenediyne metathesis, we also synthesized substrates modified at the terminal alkyne positions with silyl or ester groups. Because these substrates were inaccessible by the above described methods, we obtained the

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• behaved qualitatively similar in that they only responded to hydrogenphosphate, diphosphate, and triphosphate, the anion concentrations necessary to induce visual changes depended sensitively on the extent of the surface functionalization. NP4-Zn with the lowest amount of surface-bound recognition units

• which the redissolution of the precipitates occurred are summarized for all investigated nanoparticles in Table 1. While the general course of all titrations was similar, characteristic effects of the degree of functionalization on the behavior of the nanoparticles were observed. For NP4-Zn, diphosphate

• detrimental for the sensitivity, maybe because efficient crosslinking required a large number of anions to overcompensate potential repulsive interactions between unused surface-bound zinc complexes when the degree of the surface functionalization was high. However, the weak and unspecific response of NP35-Zn

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• opposite effects. The basic SN4 and SN4'' frameworks represent novel core molecules for further functionalization, for example with terminal acceptor groups, leading to highly absorbing dye molecules for application in organic solar cells. Heteroacenes: tetrathienoacene (TTA), S,N-heteroacenes SN4, SN4

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• /ammonium (pseudo)rotaxanes. One reason is that functionalized crown ethers can cause major obstacles in the synthesis of (pseudo)rotaxanes, as their functionalization can strongly interfere with the binding properties of the crown ether [24][25]. Recently, we have investigated examples for redox-switchable

• redox-active units were investigated with respect to the impact of the functionalization on the thermodynamic binding properties towards secondary ammonium axles using isothermal titration calorimetry (ITC). The electrochemical switching properties of the redox-active crown ethers were examined using

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• cyclic olefins, such as diesters, imides, and lactams with varied functionalization patterns and different structural architectures is described. The synthetic methodologies were based on electrophilic activation through halonium ions of the ring olefin bonds, followed by nucleophilic fluorination with

• Deoxo-Fluor®. The fluorine-containing products thus obtained were subjected to elimination reactions, yielding various fluorine-containing small-molecular entities. Keywords: fluorine; fluoroselenation; functionalization; halofluorination; stereocontrol; Introduction The effects of fluorine on

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• offer various possibilities for functionalization. Therefore, TBTQ derivatives have attracted much attention since the first synthesis reported in 1984 [21][22][23][24]. The arene periphery of the TBTQ framework bears a great and variable potential for the efficient expansion of the small and relatively

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• different approaches have been developed that use a single catalyst. Alemán et al.’s approach combines the two catalytic motifs into a single bifunctional catalyst 38, using thioxanthone as the chromophore (Scheme 5) [31]. The catalyst 38 was then applied to known reactions such as the α-functionalization

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• Fujita et al. [9][10][11] or stereoselective nucleophilic substitutions by Raymond et al. [12] are important examples in this context. Recently, we described the use of hierarchically assembled helicates as templates for stereoselective Diels–Alder reactions via a post-functionalization process [13

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• promising building blocks for further functionalization, including (het)aryl or alkenyl substitution at the N1 atom. However, direct arylation of 1 with aryl halides under Ullmann reaction conditions is a low-efficiency process giving only complex mixtures. It is likely that the harsh thermal conditions

• pyrimidin-2(1H)-ones 5a–e exhibit fluorescence properties with emission of λmax = 490–532 nm in CH2Cl2 solution. In order to analyze the effect exerted on the Chan–Evans–Lam arylation by 4-, 5-, and 6-substituents on the pyrimidine ring and also aiming at the further functionalization of pyrimidin-2(1H)-one

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• characteristics generally associated to dextran polysaccharides: they are highly soluble in water, biodegradable, biocompatible, commercially available, and cheap. Furthermore, the presence of hydroxy groups allows for an easy chemical functionalization with complementary functional groups. Indeed, dextrans and

• short reaction time, reactant economy, higher degree of functionalization, and solvent-free conditions, compared to solution-based routes are discussed. The dextran mechanochemically conjugated to PBA-BODIPY (Dex-1b, Figure 1) formed nanoparticles through self-assembly retaining the fluorescent

• conventional solution-based (in batch) protocols were investigated. In solution, dextran functionalization was carried out following a modified protocol recently reported on the conjugation of PBA to dextran [27]. This protocol was based on a conventional solution-based approach [27], where a significant

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• sumanene (2), it is not only gifted with three benzylic positions stapled between the benzene rings of the triphenylene system but also possess the bowl-curvature which enables stereoselective functionalization at these valuable positions. Taking the advantage of these benzylic positions, two years later

• corresponding compounds 42 and 43, displayed in Scheme 7 [36][37][38]. Fascinatingly, the group of Sakurai has revealed the exo-functionalization of trimethylsumanene 28 to produce the products 45a,b stereoselectively, as can be inspected from Scheme 8 [39]. The preparation of the compounds 45a,b were achieved

• mono-substituted sumanene derivatives 49b–d in a stereoselective manner as can be inspected from Scheme 10 [41][42]. In another event, Amaya, Ito, Katoh and Hirao reported a vital building block 53 to extend the π-conjugation bidirectionally through regioselective functionalization (Scheme 11) [43]. To

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• of aryl triflates [29] and arylpalladium complexes [2][47], few permit a one-step transformation of unactivated C(sp3)–H bonds to C(sp3)–F bonds [1][3][36][38][48]. Such a transformation would be highly valuable for the late-stage functionalization (LSF) of complex molecules, such as those in Scheme

• . The authors demonstrated that the transition state for Selectfluor® undergoing HAT at this position (see TS1) was more kinetically accessible, despite the bond dissociate free energies (BDFEs) suggesting C3 functionalization (Scheme 27). 3.4 Directing-group-guided benzylic C–H fluorination In another

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• , implicated in protein folding and structural stability, and mediating interactions with receptors and with the environment. All N-glycans share a common core from which linear or branched arms stem from, with functionalization specific to different species and to the cells’ health and disease state. This

• this study indicated a clear sequence-to-structure relationship, especially in the context of the dynamics of the (1-6) arm. More specifically, we found that the outstretched (open) conformation of the (1-6) arm gets progressively less populated as the functionalization of the arm grows, i.e., from 85

• % in Man3, to 52% in (F)A2, (F)A2[3]G1, and (F)A2[3]G1S1, where the (F) indicates the presence or absence of α(1-6) core fucosylation, to 24% in all structures with (1-6) arm terminating with Gal-β(1-4)-GlcNAc or Sia-α(2-6)-Gal-β(1-4)-GlcNAc, irrespective of the functionalization of the (1-3) arm [24

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• Ugi reaction we have attempted to stereodefine the chiral center at the peptidyl position through the post-Ugi functionalization. In order to achieve this, we chose to study 2-oxo-aldehyde-derived Ugi adducts many of which partially or fully exist in the enol form that lacks the aforementioned chiral

• major slow enantiomer was successfully established as S (Figure 1). Conclusion In summary, we have explored a new strategy for controlling the stereochemistry in the Ugi adducts through the enantioselective post-Ugi functionalization. Specifically, we have adapted the cinchona alkaloid-promoted

• enantioselective post-Ugi functionalization. Funding This work was supported by the start-up fund from Soochow University (grant Q410900714), National Natural Science Foundation of China (grant 21650110445), Natural Science Foundation of Jiangsu Province of China (grant BK20160310), the Priority Academic Program

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• was achieved but also with impurities. This route was not investigated further, and instead functionalization of alkene E-1d was explored. Direct ring-opening reactions of fluoroalkylidene-oxetane 1 with heteronucleophiles were previously explored and success was only possible with thiols, such as

• mercaptobenzothiazole (Table 1). However, the reaction was not selective and afforded a mixture of E/Z alkenes 1c. The functionalization of alkene E-1d via displacement of the bromine atom (Scheme 8), with nucleophiles such as CsF and NaN3 was then studied. When the reaction was performed in DMF products E-23 and Z-24

• due course. Conclusion The selective synthesis of tetrasubstituted E- or Z-fluoroalkenes was achieved by ring-opening reactions of fluoroalkylidene-oxetanes, with the presence of the fluorine atom governing regioisomeric attack of the bromide ion. Functionalization of the resultant bromoalcohols with

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• previous functionalization, thus considerably reduce waste generation and a number of synthetic steps. In parallel, transformations involving photoredox catalysis promote radical reactions in the absence of radical initiators. They are conducted under particularly mild conditions while using the visible

• catalytic system is extremely appealing. In that perspective, the scope of this review aims to present innovative reactions combining C–H activation and visible-light induced photocatalysis. Keywords: C–H activation; C–H functionalization; dual catalysis; photoredox catalysis; radical chemistry

• -transfer-type reactions under mild conditions and in the absence of toxic radical precursors [44][45][46]. Considering, on one hand, the fundamentally appealing properties of both, metal-catalyzed C–H functionalization reactions and visible-light-induced photocatalysis, and, on the other hand, their

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• a multistep synthesis route. A first approach relied on the nucleophilic substitution of chlorine in cyanuric chloride with Grignard reagents, ammonia or amines [25][26], which suffered from the high reactivity of the Grignard reagents that prevents further functionalization. Moreover, this protocol

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• cycloadditions with model alkynes. Besides two ortho- and para-bromo-substituted benzaldehydes, the azide functionalization of a fluorene-based structure will be presented. The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of the so-synthesized azide-functionalized bromocarbaldehydes with terminal

• synthesis of ESIPT-based luminophores [70][71][72]. Herein, we present the efficient functionalization of derivatives of the potent luminophores 1 and 2 with “clickable” azide functionalities to target the structures 3–5 and further investigated the influence of this functionalization, both in the unlinked

• bromocarbaldehydes 3, 4, and 5 were successfully isolated in excellent yields of >90%. As a further model functionalization, the sterically demanding adamantyl substituted triazole 42 was subjected to a methylation reaction with Meerwein′s salt (trimethyloxonium tetrafluoroborate) to deliver the N-methylated

Mechanochemical green synthesis of hyper-crosslinked cyclodextrin polymers

• Alberto Rubin Pedrazzo,
• Fabrizio Caldera,
• Marco Zanetti,
• Silvia Lucia Appleton,
• Nilesh Kumar Dhakar and
• Francesco Trotta

Beilstein J. Org. Chem. 2020, 16, 1554–1563, doi:10.3762/bjoc.16.127

• by washing with water at 40 °C leading to carbonate NS. On the other hand, the presence of a “tunable” quantity of remaining reactive groups could be used for further functionalization. In the present work this was demonstrated by a straightforward covalent coupling of the synthesized cyclodextrin

• nanosponges with selected organic dyes that are used as probe molecules with different structures (methyl red, rhodamine B, and fluorescein). The simple functionalization of the cyclodextrin NS, in this case via reactive imidazole moieties, is particularly interesting for a variety of applications. For

• were comparable). Hydrolysis, in fact, affected only the imidazolyl carbonyl groups and not the carbonate bond of the CD-NSs. In order to confirm the presence of reactive imidazolyl carbonyl groups, which would make the functionalization of NS possible, an attempt was made on βNS-CDI 1:8 by using

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• functionalization of C–H bonds is a powerful strategy for the synthesis and derivatization of organic molecules [12]. Homogeneous catalysis employing transition metal complexes has been widely accepted as one of the most efficient ways to perform C–H activation-based synthesis with high selectivity under relatively

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• with the reaction conditions and yielded the corresponding products (6oa–va, 48–92%), allowing for further functionalization through subsequent transition-metal-catalyzed coupling reactions. Intriguingly, it was found that compounds with bicycloaryl and heteroaryl ring systems were also viable

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• . Under photoirradiation, organic disulfides can be easily cleaved into free thiyl radicals (RS•) and can reversibly add to unsaturated multiple bonds to catalyze a variety of functionalization reactions under mild conditions. In photoredox catalysis reactions, an excellent electron transfer ability and

• engage with the peptide backbone via an H-bonding interaction, and in order to achieve a high enantioselectivity, the amide functionalization of the peptide at the 4-proline position is essential. Amide-substituted vinylcyclopropanes have a relatively good H-bond-donating ability, so they are more

• of the aromatic S–S bond by visible light. In 2019, Meng and co-workers reported a visible light-mediated disulfide-catalyzed metal-free and base-free α-functionalization of 1,3-dicarbonyl compounds [17]. Under visible-light irradiation, the α-hydroxylation or α-hydroxymethylation of 1,3-dicarbonyl