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

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• , and gives a mixture of 1,4- and 1,5-triazole regioisomers (Scheme 1) [39]. Interest in and applications of the AAC have surged over the past 15 or so years, since the introduction of Cu(I) catalysis, which led to significant improvements in both the regioselectivity and rates of the reaction [40][41

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• includes the reduction to form alkane 8 [3], oxidative cleavage of the C=C bond to form 9 [4], ring-opening metathesis to form functionalized alkenes 10 and 11 [4], dihydroxylation to form diol 12 [5], ruthenium-catalyzed [2 + 2] cycloaddition with unsymmetrical alkynes to form regioisomers 13 and 14 [6

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• additional desulfonylation step (Scheme 6) [13]. Both electron-withdrawing and electron-donating groups on para-position of the aryl ring were tolerated, and provided comparable yields. On the other hand, the presence of a substituent in meta-position led to the formation of two regioisomers. As for ortho

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• failed to give the expected product. With a substituent at the meta-position of the aniline ring, a mixture of regioisomers was obtained. Various alkenes with substituents (R3) were investigated and the oxindoles were obtained in moderate to high yields (Scheme 24). Simultaneously, Lei and co-workers

• -substituted phenyl rings produced mixtures of regioisomers. Under these metal-free conditions, it was proposed that the CF3 radical was formed uniquely by reaction of CF3SO2Na with K2S2O8. N-Arylacrylamides could also react with CF3SO2Na under metal-free conditions by replacing tert-butyl hydroperoxide or the

• arenes and heteroarenes: In 1991, Langlois and co-workers reported the first trifluoromethylation of aromatic compounds with sodium trifluoromethanesulfinate under oxidative conditions (Scheme 34) [16]. The scope was quite narrow with electron-rich aromatics and mixtures of regioisomers were often

An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• regioisomers, out of which the desired anhydroMurNAc derivative 1 could only be isolated in trace quantities from the mixture with isomers 5–11 (Scheme 2). A selective protection of the 4-OH position of 4 has been reported, and as such this tritylation was carried out, delivering 12 in 74% yield [12]. The

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate

• Clément Ghiazza,
• Anis Tlili and
• Thierry Billard

Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260

• . Further, a high regioselectivity is observed but, surprisingly, the anti-Markovnikov regioisomers were obtained. The stereochemistry and regiochemistry were confirmed thanks to the X-ray structure of compound 3a (Figure 1). From a mechanistic point of view, the reaction starts certainly with the

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• Michael-type regioisomer 5a (Table 1, entry 1). The reaction course and the ratio of the regioisomers formed were conveniently monitored by 19F NMR spectroscopy. Acid 4a precipitated in pure form on evaporating toluene and treating the residue with diluted hydrochloric acid. Performing the reaction in a

• it under optimal conditions using toluene or DMSO as solvent and TEA (1 equiv) as catalyst (Table 2). The alkyl substituent at the nitrogen atom of the substrate had no significant effect on the reaction course. In all cases, both regioisomers, 4b–i and 5b–i, were isolated in modest to high yields

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• spectroscopy. For monocyclic derivatives of azoles, the structures of N-alkylated regioisomers can be determined using 2D H-(C)-N multiple bond correlation (HCNMBC) experiments [22][23] using natural isotopic abundance. These experiments rely on the magnetization transfer through 13C-15N J-coupling constants

• ]pyrimidin-7-one and the N-adamantylation of the obtained compounds. The combined analysis of the JCN and JHN couplings permitted the straightforward determination of the adamantylation sites in these azolo-azines, even when a mixture of regioisomers is formed. Results Synthesis. Derivatives of 1,2,4

• adamantyl cation generated from 1-adamantanol in acidic medium [34][35][36][37]. The adamantylation of 13-15N2 led to N2- and N1-regioisomers (15a-15N2 and 15b-15N2, respectively, Scheme 1). Interestingly, according to the possible resonance structures, compound 15a-15N2 should represent a mesoionic