Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• shift to 673 nm (Table 8, entry 7). Most remarkably, the regioisomers 6c and 6e differ quite significantly with respect to their fluorescence quantum yields Φf. While chromophore 6e only emits with an efficiency of 1%, the regioisomer 6c accounts for an extraordinarily high relative quantum yield of 99

• ·10−29 C·m). All α-pyrones 6 fluoresce in the solid state (Figure 8, bottom) and for five selected α-pyrones 6 the emission maxima were determined (Figure 14, Table 9). The fluorescence maximum of unsubstituted α-pyrone 6a lies at 499 nm and the maxima of the monomethoxy-substituted regioisomers 6b

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• amide, a mixture of the two possible regioisomers of compounds 4k, 4l and 4m was obtained. Fortunately, the major isomers (shown in Scheme 3) could be isolated as pure products corresponding to the less hindered isomer, in which the annulation took place in the para-position of the halogen. When a Me

• ), isocyanide (1.1 equiv) and TMSN3 (1.1 equiv) in EtOH at 100 °C (MW radiation, two cycles of 15 min each). Influence of substituents R and R2 on the reaction outcome. For compounds 4k–m the overall yield in parentheses refers to the mixture of regioisomers. Influence of the alkyne and R1 substituent on the

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Design of a double-decker coordination cage revisited to make new cages and exemplify ligand isomerism

• Sagarika Samantray,
• Sreenivasulu Bandi and
• Dillip K. Chand

Beilstein J. Org. Chem. 2019, 15, 1129–1140, doi:10.3762/bjoc.15.109

• positional isomer or regioisomer of L2) in order to exemplify ligand isomerism. Ligand isomerism includes metal complexes (at least two) having the same molecular formula but are composed of different positional isomers (regioisomers) of the ligand. Positional isomers (regioisomers) of a non-chelating ligand

• , though in small proportions, using ligand L1 but not L2. The ligands L1 and L2 are positional isomers (regioisomers) hence many of their complexes could be rightfully considered under ligand isomerism in coordination complexes. Experimental Synthesis of ligand L1: A mixture of pyridine-3,5-diyldimethanol

• − 4NO3]4+. The ligands (i) L1 and (ii) L2 that are positional isomers (regioisomers). Partial 1H NMR spectra in DMSO-d6 for (i) L1, (ii) [Pd(tmeda)(L1)](NO3)2 (1a) and (iii) a mixture of [Pd(tmeda)(L1)](NO3)2 (1a) and [Pd3(tmeda)3(L1)2](NO3)6 (2a). Partial 1H NMR spectra in DMSO-d6 for (i) L1, (ii) [Pd

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• disubstituted derivative of cinchona alkaloid–non-methylated CD was developed. The prepared derivative was subsequently tested in an AAA reaction. In contrast to the monosubstituted derivatives, disubstituted CDs should be considered as possible mixtures of regioisomers and pseudoenantiomers [31][32]. Because

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• -benzyladenine (25) afforded the corresponding N9-regioisomers as the major product as determined by 1H NMR spectroscopy (Scheme 6a,b). The major isomers were then isolated and subsequently converted to phosphonate 6 in order to confirm the degree of regioselectivity. Interestingly, the amidine moiety in 28

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physicochemical properties. The primary-side homo-difunctionalization of β-CD can lead to three regioisomers, while the hetero-difunctionalization

• the corresponding pure diazido regioisomers. Direct monotosylation of 6-monoazido-β-CD or monoazidation of the single regioisomers 6A,6X-ditosyl-β-CDs afforded hetero-difunctionalized 6A-monoazido-6X-tosyl-β-CDs in significant yields. Overall, the single regioisomers, 6A,6X-ditosyl-, 6A,6X-diazido

• very challenging to prepare due to the fact that in addition to regioisomers, pseudoenantiomers are unavoidably formed that have the same substitution pattern, but mirror-image relationship between the arrangements of substituents [19]. This phenomenon has an amplified effect in applications which are

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• -consistent reaction field, SCRF) were simulated by using the CPCM method in DMSO as a solvent. The zero-point vibrational energy corrections were done without scaling. Three typical conformers of quercetin (2) were considered (Figure 3). These are the regioisomers with respect to the direction of the OH

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• molecules 8–10, in 60%, 53% and 49% yields, respectively. Such well-known π-nucleophiles as phenols could be used for the reaction, though 3-methoxyphenol and 3,5-dimethoxyphenol gave inseparable mixtures of regioisomers 11a and 11b (NMR, LCMS). The reactions with p-isopropyl- and p-tert-butylphenols gave

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• ). The chlorinated compound 2,5-dichloro-1,3-dimethoxybenzene (46) was also rigorously identified by comparison to all possible regioisomers that we had synthesised in a previous study [18]. Interestingly, the substitution pattern for the compound from H. macrocarpum is different to an isomer from the

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• , Hungary Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary 10.3762/bjoc.14.262 Abstract Novel 2- or 4-phosphonated 13α-estrone derivatives were synthesized via the Hirao reaction. Bromo regioisomers (2- or 4-) of 13α-estrone and its 3-benzyl or 3-methyl ether were

• , only 2-regioisomers displayed substantial inhibitory action, which did not depend on the hybrid state of carbon attached to C-2 [22]. Phan et al. described that halogenation of ring A of estrone is a powerful strategy in the synthesis of effective STS inhibitors [25]. Certain 4-halogenated estrone

• 7b differing in size and polarity (Table 2, Scheme 1). In certain cases (Table 2, entries 2–6 and 8–12), however, it was necessary to change the optimal conditions (Table 1, entry 10) concerning reaction time and temperature. 2-Regioisomers 1–3 could successfully be transformed without significant

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• regioisomers on the primary rim of homobifunctionalized diazido-α-CDs by selective substitution on the primary rim. Specifically, three positional regioisomers 6A,6B-, 6A,6C-, and 6A,6D-diazido-α-CDs were prepared via different intermediates (using sulfonylation with capping agents, bromination and tosylation

• ). Furthermore, heterobifunctionalized 6A-azido-6X-mesitylenesulfonyl-α-CDs were also synthesized, and all regioisomers were successfully separated by HPLC. Moreover, the heterobifunctionalized α-CD regioisomers were isolated in gram-scale quantities, isomers AB and AC in the form of a pseudoenantiomeric mixture

• ; heterobifunctionalized alpha-cyclodextrin; homobifunctionalized alpha-cyclodextrin; regioisomers; regioselectivity; Introduction Cyclodextrins, cyclic cone-shaped oligosaccharides [1], have long attracted interest for their properties in host–guest complexes both in research and in pharmaceutical and food industry

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• nitroacetate and organic azides, in which the synthesis of both triazolocoumarin regioisomers was accomplished [33]. Interestingly, the expected regioisomer was not observed in the case of the in situ formed 3-nitrocoumarins. Hence, in our continued exploration towards novel multicomponent reactions for the

• , in which we synthesized the different regioisomers 5a, 10 and 11 via different pathways (Scheme 2). The regiospecific syntheses [36] of compounds 5a and 11 were accomplished by triazolization of the corresponding flavanone 7 and 2-phenylchroman-3-one (8), respectively. As anticipated, these methods

• furnished both regioisomers in poor yields since the chromanones 7 and 8 are known to be unstable under the triazolization conditions [36]. Hence, no further attempts were made to improve these yields. Additionally, NH-triazole 9 could be alkylated using benzyl bromide and potassium carbonate in acetone

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• pyrones 44a–g in good-to-high yields within 1 h (Scheme 40). Ester, ketone, and hydroxy groups were tolerated in the reaction. In the case of an unsymmetrical diyne bearing methyl and isopropyl groups (43g), a mixture of regioisomers 44g + 44g′ was obtained in high yield with high regioselectivity. For

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

• Xiaoshen Ma and
• Seth B. Herzon

Beilstein J. Org. Chem. 2018, 14, 2259–2265, doi:10.3762/bjoc.14.201

• -methoxybenzoate (3a) with N-methoxypyridinium methyl sulfate (6c) to form the hydropyridylation product 4l in 66% yield and as a 4.7:1 ratio of regioisomers (Table 1, entry 13). We also demonstrated that the alkyl radical generated from the HAT process can be trapped by (η6-benzene)manganese tricarbonyl

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• -oxyimidation of vinylarenes with I2/PhI(OAc)2 system. Reaction conditions: vinylarene 1a–k (0.5 mmol), N-hydroxyimide 2a,b (0.5 mmol), I2 (0.25 mmol), PhI(OAc)2 (0.3 mmol), DCM (3.0 mL), 20–25 °C, 10 min, under air. rr = regioisomers ratio. aIBX (0.5 mmol) was used instead of PhI(OAc)2, reaction time: 24 h

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• -acetoxysulfenylation of aliphatic alkenes in moderate to good yields but the products are obtained as a mixture of two regioisomers. In the case of cyclohexene, the reaction gave the corresponding 1,2-acetoxysulfide product as a single isomer. Similar results were reported by Marakalala and Kinfe where a catalytic

• [73] (Scheme 39). The reaction was found to be useful in both intra- and intermolecular thioetherification to yield the regioisomers in ratios that were dependent on the steric bulk of the substituents on the alkene (Scheme 39). The reaction was proposed to proceed via initial transfer of the thiolate

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• by Taran et al. [4]. In order to avoid duplication our review is therefore focused in more detail on thermal, photochemical as well as metal-catalyzed reactions of sydnones with alkynes and factors that influence the yield and ratio of both possible regioisomers and also the kinetics and mechanism of

• Huisgen et al. found that some non-symmetrical alkynes (oct-1-yne, phenylacetylene and especially methyl propiolate) gave mixture of both pyrazole regioisomers. The following Table 4 summarizes all known examples [1][2][8][20][24][32][33][34][36][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80

• ][81][82][83][84][85][86][87][88][89][90][91][92][93] where the ratio of both possible regioisomers or at least chemical yield of the major regioisomer was given. The first people who qualitatively discussed the regioselectivity on the basis of semi-empirical quantum calculations was Houk et al. [94

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• partially or completely saturated in order to get stereochemically different compounds for structure–activity determinations. The saturated derivatives contain a phenyl moiety at C-2 attached through an ethenediyl or ethanediyl linker. Of the synthesized 2- and 4-regioisomers, solely the 2-counterparts

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• departure of the 5´-linked nucleoside by a factor of 107. The mechanistic proposal has partly been based on Breslow’s studies on hydrolysis of 4-tert-butylcatechol cyclic phosphate by regioisomers of β-cyclodextrins bearing two imidazole groups [60]. This reverse reaction of the cyclization of 4-tert

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• α-cadinene (5). The same problem applies to the unambiguous identification of regioisomers of aromatic compounds. We have recently reported on the GC–MS-based identification of the fungal volatiles 1-chloro-3,4-dimethoxybenzene (6) and 1,3-dichloro-4,5-dimethoxybenzene (7) from an endophytic

• Geniculosporium sp. by comparison of the natural products to all possible regioisomers that were obtained by chemical synthesis [9]. Here we report on the identification of the volatiles emitted by the xylarialean fungus Hypoxylon invadens MUCL 54175, a highly interesting pyrenomycete that was recently described

• unambiguous GC–MS-based structural assignment was only possible by comparison to all regioisomers with different substitution patterns at the benzene ring. Results and Discussion The volatiles released by agar plate cultures of Hypoxylon invadens MUCL 54175 were collected through the CLSA headspace method and

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• the amount of diene to 5 equiv, the HDA adducts 3ad–3cd and 3ae–3ce were obtained in moderate to good yields (3ad–3cd: 55–73%, 3ae–3ce: 49–65%; Table 2, entries 8–13). The HDA adducts 3ae–3ce derived from 2e were isolated as mixtures of regioisomers (distal:proximal = 2:1 or 1:1 as determined by 1H

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• partially purified by acetone precipitation and extraction with 60% methanol. The crude N-glycans were found to be a rather complex mixture of compounds, the four major components of which were identified as triantennary glycans with 2 or 3 sialic acids attached as regioisomers (i.e., both α(2–6)- and α(2–3

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• acetic acid (Scheme 1). In the same report the other regioisomers 6-trifluoromethylpyrazolo[3,4-b]pyridines 20 were obtained under multicomponent solvent-free conditions by the reaction of hydrazine 14, β-ketonitrile 15 and β-diketone 17 as an exclusive product. The structures of both the regioisomers

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• substituents and generate mixture of regioisomers in some cases. In 2012, the group of Qing [56] designed a copper-catalyzed oxidative trifluoromethylation of heteroarenes and electron-deficient arenes with TMSCF3 through direct C−H activation (Scheme 35). At first, the oxidative trifluoromethylation of 1,3,4

• . These methods have often the drawback of generating mixtures of regioisomers. Future efforts will be focus on developing efficient and less expensive reagents, along with a better understanding of mechanisms, improving the regioselectivity and enantioselectivity in these trifluoromethylation processes