Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• -substituted analogues with interesting three-dimensional character, including chiral cyclopentane-1,2-diol and -1,2,3-triol derivatives. This unusual substitution pattern provides a useful starting point for the discovery of novel bioactive molecules. Keywords: diol synthesis; nucleoside; PreQ0

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• , attempts to move away from 2b to less electron-rich dienes such as 2c, 2d and 2e (Table 1, entries 2–4), failed to produce any of the desired endoperoxide products and mainly oxidative cleavage adducts were observed. Given the lack of reactivity of this alkene substitution pattern, we turned our attention

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• depends on the choice of potential reaction partners, but also on its substitution pattern and the reaction conditions. As examples, when N1 is substituted with a methyl group, the carbene can be trapped by elemental sulfur, isocyanates, and isothiocyanates which form indazolethione 4, indazolium-3

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• ]. Depending on the substitution pattern for the central 2,2’-bipyridines, three conceptually different types of allosteric receptors can be obtained: 4,4’- or 6,6’-substitution, both leading to positive allosteric receptors, meaning that they adopt an open anti-conformation in the free state where the two

• on-state in the absence of the effector and changes its conformation to the open off-state upon binding of it. In this article we present the synthesis of three new cyclodextrin-functionalised 2,2’-bipyridines 1–3 differing in the bipyridine’s substitution pattern (Scheme 2) and their metal complexes

• well defined [Zn(1)2] complexes which, together with the NMR data, proof that zinc(II) ions are suitable to act as an effector for 1. Changing the substitution pattern to 6,6’ like in ligand 2, however, makes it impossible to form a 1:2 complex due to the steric crowding around the metal binding site

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• to prepare the spirooxindoles with this novel substitution pattern. Thus, the acid additives were examined and the optimization results are listed in Table 2. To our delight, the addition of 4-nitrobenzoic acid reversed the regioselectivity of this reaction, and the ratio of 5a/4a was increased from

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• -selective fashion, as the cis-isomers are generally thermodynamically favored even with large R-groups on the exo-nitrogen substituents [39][40][41]. The situation is less clear for N(ring)-aryl-cyclodiphosphazanes, in which, dependent on the substitution pattern either cis or trans-isomers are favored [42

• yields but a lower enantioselectivity. Chlorine and fluorine in meta-position also lead to diminished yields and lower enantioselectivities (Table 3). Concerning the substitution pattern a clear trend that correlates the increasing electron-withdrawing properties of substituents on the phenyl ring with

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• natural product. To unambiguously prove the substitution pattern at the aromatic ring system, the phenolic OH-group was selectively methylated using diazomethane. The resulting methyl ether was irradiated in a 1D NOE experiment, which resulted in the expected strong increase of the proton bound to C-6

• of existing coumarin structures in literature, the 5-hydroxy-7-nitro substitution pattern combined with the unusual long-chain, fully saturated alkyl substituent at C-4 are unique to the myxcoumarins 7 and 9. With the production of myxothiazol A (5) and aurachin A (6), the investigated strain

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• describes the cyclization of differently substituted derivatives under identical conditions. Notably, the yield of macrolactones is significantly affected by the substitution pattern and increases from 27% for the unsubstituted lactone 34 (Scheme 7) to 53% for the 9-methyl-substituted derivative 36 (Scheme

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• , although giving lower yields. A broad substitution pattern on the (hetero)aryl ring was compatible with the reaction, and the “imino” C–H was selectively trifluoromethylated (Table 18). When carrying out the reaction in the presence of TEMPO, the desired reaction was almost completely shut down, while a

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• rosiglitazone (1.40) with its structure only differing in the substitution pattern of the parent pyridine ring. Its synthesis begins with the hydroxymethylation of 2-methyl-5-ethylpyridine (1.11), a commodity chemical obtained from the condensation of acetaldehyde with ammonium acetate (Scheme 12) [43]. At

• from the bacterial cell. Due to the elaborate substitution pattern of the parent quinolone ring systems these compounds are usually prepared via a linear consecutive sequence. In the case of moxifloxacin, an intramolecular base catalysed nucleophilic aromatic substitution is used to prepare the

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• potential allylic radicals like 11-R1 and 11-R2, 11-R3 is up to 8 kcal/mol more stable. Within the subset of allylic radicals that differ only by their alkyl substitution pattern (11-R1, 11-R2, 12-R1 and 12-R2) the energetic differences are less pronounced. Equally, the reasons for the small variations in

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• substitution pattern of the D-ring bares most of the functionalities, i.e., a secondary and a tertiary alcohol, the former of which is commonly glycosylated with 2,6-dideoxy sugars (Figure 1) [3]. These carbohydrates are of highest importance for the biological activity of anthracyclines and bind to the minor

• ]. Opening of the silyl ether moiety was accomplished by treatment with TBAF in quantitative yield and gained access to the natural substitution pattern of the carbohydrate backbone. It was not possible to open the silyl ether moiety of 26 by the utilization of Cs2CO3 in methanol starting from 13 as

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• process competition scenario. The noticed scope endorses an active involvement for a highly reactive gold–vinylidene intermediate as responsible for the selectivity of the eventual cyclization step, in agreement with the tentative mechanistic rationale depicted in Scheme 4A. Though the substitution

• pattern is not the one commonly associated with conventional electrophilic aromatic substitution reactions, other mechanism should not be disregarded on the basis of the structure of the final product. So, the alternative mechanistic description summarized in Scheme 4B cannot be firmly rejected, at the

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• (1,3-dihydro-2H-isoindole-1,3-dione, 4) substitution pattern. The isoindole structure has attracted scientists for decades and can be found in several natural and pharmaceutical compounds [2][3]. A number of structures were explored over the years and promising drug conjugates such as 5–11 could be

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• were observed. Benzo[ghi]perylenes are typical byproducts observed in the photocyclization of [5]helicene-like molecules. Reactions to obtain selectively helicenes or benzo[ghi]perylenes, regardless of the substitution pattern, are still a challenging task. A functionalizable [6]helicene (2r) was

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• . These results are summarized in Supporting Information File 1. Effect of m,m’-disubstitution The second substitution pattern investigated is the m,m’-disubstitution. By adding both substituents, the problem of the regioselectivity of addition to the arene is circumvented. The examples and results are

• radical center is not too electrophilic. Concerning the substitution pattern of the arene it was found that electron releasing substituents accelerate the addition whereas strongly electron withdrawing substituents like acyl groups retard the addition. Para-substitution has a stronger influence than meta

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• thermolysis perform intramolecular C–H insertions to produce α-halo-β-lactams. When carried out with α-bromodiazoacetamides bearing cyclic side chains, the thermolysis reaction affords bicyclic α-halo-β-lactams, in some cases in excellent yields, depending on the ring size and substitution pattern of the

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• and cyclopentane-1,3-diyls. Experimental investigation of the chemistry of singlet diradicals has become possible. The present study explores the substituents and the effect of their substitution pattern at the C(1)–C(3) positions on the lifetime of singlet octahydropentalene-1,3-diyls to understand

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• obtained when R1 = OMe, SPh, SMe, and NMe2, at −80 °C in toluene as solvent. The influence of the substitution pattern in the aromatic ring on both the yield and the enantioselectivity is not clearly established. The introduction of electron-deficient substituents may require higher temperatures for the

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• shown in Scheme 2. We recently demonstrated [20] that variation of the aromatic substitution pattern had only a marginal influence on the HDAC inhibitory potency of psammaplin A analogues in vitro. Therefore, the native phenol was replaced by its methylated homologue for ease of synthesis, notably to

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• -dihydropyridine derivatives, which were obtained in virtually pure form in crude reaction mixtures. As evidenced with these results, 3-aryl-1,4-dihydropyridines and pyridines (5/6a–f and l–r) are readily obtained from the corresponding aryl-substituted N-allyl-ynamides regardless of the substitution pattern or

• conditions. The influence of the substitution pattern of the allyl moiety was next carefully examined and substitution at the β-, γ-positions, or both, was well tolerated, yielding the 3,5-disubstituted- (5/6l–o), 3,4-disubstituted- (5/6p–q) and 3,4,5-trisubstituted- (5/6r) 1,4-dihydropyridines and pyridines

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• consecutive carbon atoms, but the system is either lacking the desired substitution pattern or the proper degree of unsaturation (C6 + 0). A fourth possibility, the coupling of three C2 units (C2 + C2 + C2) is extremely rare and it appears that only two examples have been reported so far (see Scheme 12 and

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• by Schipper [20] and Kaneda [21], based on detailed NMR studies. According to them, the bottromycins are cyclic tetrapeptides, connected to a tripeptidic side chain through an amidine structure. The different bottromycins differ only in the substitution pattern of the proline (Figure 1). The three

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• ring fusion of C4a–N8 (1, 3 and 4) or C8a–N5 atoms (2), and differ in the arrangement of the substitution pattern of the imidazotriazine framework (Figure 1). The structural variation of imidazo[1,2,4]triazine derivatives poses a significant challenge, particularly if a broad variety of substituents is

• regioselectivity depended on the substitution pattern of 6, due to the directing effect of the methyl groups. Thus, traces of a N1-substituted regioisomer were detected by LC/ESI-MS analysis in the conversion of 5 to product 7 (N3/N1-alkylation ratio 15:1). Direct N1,N3-dialkylation of 5, however, was not observed

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• thiourea core via the sulfonimidoyl nitrogen. They differ in their aryl substitution pattern. Copper-catalyzed arylation of (S)-2 with 2-iodonitrobenzene gave rise to coupling product (S)-10 in excellent yield (98%). After subsequent reduction of the aromatic nitro group to give aniline (S)-11 in 83% yield