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

• improve the rate and modulate the regioselectivity and enantioselectivity of reactions [11]. For example, metal-based CD catalytic systems and CD derivatives for organocatalysis have already shown promising results in the studies by Hapiot and Monflier [12], Armspach [13] and others [14][15]. The chemical

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

• tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting

• affords 20 in a comparable overall yield of 13%. We conducted a temperature, solvent and base screen to determine what impact these parameters have on the regioselectivity of the alkylation (Table 2). The overall regioselectivity appeared insensitive to the reaction conditions with only a slight decrease

• in selectivity for 6 observed when hydroxylic bases were employed in the reaction (Table 2, entries 1 and 2). Temperature was observed to have no effect on the regioselectivity (Table 2, entries 7, 9 and 10). Similarly, no improvement was observed when other aprotic solvents were used in place of DMF

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• (or amination) sequence on achiral nonfunctionalized cyclopropenes provided the desired cyclopropanol (and cyclopropylamine) derivatives in excellent diastereo- and enantiomeric excesses. Keywords: carbocupration; cyclopropanol; cyclopropene; regioselectivity; stereoselectivity; Introduction The

• facial selection by the catalyst is required: (i) regioselectivity when R1 is different to H and enantioselectivity when R1 is equal to H (left or right) and (ii) diastereotopic face selection (top or bottom) as described in Scheme 2. Since the pioneering addition of a carbon–metal bond (carbometalation

• be addressed carefully as it plays an important role in the control of the regioselectivity of the reaction pathway. An alkyl group on the C1 position of the cyclopropene should control the regioselectivity of the addition of the organometallic species to give the more stable secondary

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

• -difunctionalization; regioselectivity; Introduction Cyclodextrins (CDs) are cyclic oligomers of α-D-glucopyranose (Figure 1 illustrates the heptamer, β-CD) that have attracted worldwide interest in various fields of applied supramolecular chemistry due to their ability to form host–guest inclusion complexes [1]. A

• regioselectivity is observed. On the other hand, tosylation under aqueous basic conditions has a different reaction mechanism in which p-TsCl occupies the CD cavity prior to the reaction [23]. This orientation of the first tosyl group has a great impact on the substitution of the second tosyl moiety, which can

• ditosylation reactions and for the observed partial regioselectivity in reaction 2 (Scheme 2). Additionally, a Vilsmeier–Haack/Appel-type iodination reaction was performed with β-CD, using triphenylphosphine (PPh3) and iodine (I2) in DMF (reaction 3, Scheme 2). This reaction is known to be selective for the

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• % yield) and other compounds evidence the participation of radicals [30]. After the efficient conversion of pyrimidine N-oxide PO14 into pyrimidine PM63 no products of this type were isolated. The regioselectivity is another important feature of the Boekelheide rearrangement if alkyl groups are present at

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• , among them the aglycon of scorzodihydrostilbenes B and D. Keywords: C–H activation; hydroarylation; phenols; regioselectivity; ruthenium; Introduction Among phytochemicals with strong allelopathic effects, various natural products are found that feature the structural motif of dihydrostilbene with

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• alkyne terminus. Hydrozirconation/iodination of alkyne 17 required freshly prepared Schwartz reagent (3 equiv) and iodine (3 equiv) to obtain yields of (E)-olefin 18 above 80% with perfect stereo- and regioselectivity. For comparison, as part of a study towards kendomycin, Arimoto and co-workers had

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• -triazolylpurine and 7-deazapurine derivatives is described. A new C(2)-regioselectivity in the nucleophilic aromatic substitution reactions of 9-alkylated-2,6-diazidopurines and 7-deazapurines with secondary amines has been disclosed. The obtained intermediates, 9-alkylated-2-amino-6-azido-(7-deaza)purines, were

• reported that 2,6-diazidopurine nucleosides exhibit opposite regioselectivity with aliphatic thiols, which do SNAr reactions at C(2) position of purines [50][51]. Taking this information into account, we performed an SNAr reaction between 2,6-diazidopurine 2a and piperidine and obtained the C(2

• )-substitution product 6b as the major isomer. To the best of our knowledge, this is the first report on such regioselectivity involving combination of 2,6-diazidopurines and N-nucleophiles. It should be noted that in solution, azides 6 exist in equilibrium between the azidopurine and tetrazolopurine forms. This

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• position of the pyridinium core (see Figure 6). This regioselectivity is explained by the particular mutual orientation of the pyridinium cation and the dithionite anion and by the match of interatomic distances between the two negatively charged oxygen atoms in dithionite and the positively charged

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• ; regioselectivity; Introduction Since the discovery of the antibacterial agent nalidixic acid, as a byproduct from the synthesis of chloroquine, the medicinal interest in 4-oxoquinolines as bioactive substances has exponentially grown over the years. Nowadays, some of the most important antibiotics used in the

• discuss the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide (5). We correlate the experimental results with theoretical calculations, and with this we propose different hypotheses in the sense of better explaining the observed regioselectivity. Results

• regioselective manner, without the formation of any byproduct derived from the N-alkylation of the amide group. Structural characterization Table 1 gives the nuclear magnetic resonance spectroscopic data that allowed to confirm the structures of substances 5 and 7, and thus also confirmed the regioselectivity of

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• the properties and applications of the resulting materials. Vinylsilanes show a specific reactivity towards alkylidene ruthenium complexes because of a strong effect of the silyl group on the properties of the double bond. In general, the substituents at the silicon atom determine the regioselectivity

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• reaction between 2 and acetone. Equilibrium of oxazolidinone and enamine formation. Reaction R2: L-proline-catalyzed reaction between charge-tagged substrate 4∙Br and acetone. The regioselectivity has not been specified. 5∙Br could be either regioisomer (Scheme S1, Supporting Information File 1). Reaction

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• [62] of furanyl carbene complexes and acetylenes [63]. Angelicin (3a) was also obtained via RCM of 8-(1-propenyl)-7-vinyloxycoumarin, but the synthesis of this precursor required four steps, starting from umbelliferone, and proceeded only with moderate regioselectivity for the second step [47]. Next

• course of this study were previously described in the literature: compound 15a was used to investigate the regioselectivity of [2 + 2]-photocycloadditions [71], compound 15d was included in a comparative investigation into the fluorescence properties of 4-methylcoumarins [72], compounds 15b and 15c were

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• in the form of alkyl diacyl peroxides. This method avoids the necessity to handle organic azides, as they are generated in situ, making this protocol operationally simple. This reaction features a wide substrate scope, good functional group tolerance, high yields, and excellent regioselectivity. Most

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• biotechnological means, the protein cavity acting as second coordination sphere can be optimized to tune specificity as well as stereo- and regioselectivity. The extensive literature of artificial metalloproteins has been summarized in various comprehensive reviews [20][21][22]. One of the challenges to overcome

• weight distribution (PDI = 1.05), suggesting the living nature of the ROMP even within the protein scaffold. Neither regioselectivity (cis/trans) nor tacticity were affected [56]. The transmembrane protein FhuA The β-barrel proteins introduced for the construction of artificial metatheases up to this

• ROMP reaction, no change in regioselectivity was observed in both proteins. Within FhuA, the activity significantly dropped. This observation suggests that a particular fine-tuning is required to optimally utilize the combination of the metal catalyst with the spacing unit and the protein‘s precise 3D

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

• ; 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

• practically no regioselectivity was observed. On the other hand, the dibromo-α-CD derivative was also prepared using a four-step indirect method involving DIBAL-H deprotection (reaction 4, Scheme 2) [10][30]. This method generated the AD regioisomer exclusively without AB or AC regioisomers as byproducts

• mesitylenesulfonyl moiety instead of the tosyl group to the β-CD skeleton was first reported in the study by Tang et al. [32] who observed regioselectivity for the AC isomer. In turn, the azido functional group was selected for its stability and versatility of subsequent modification: this group can be reduced to an

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• acceptors and donors are made from common building blocks, limiting protective manipulations, and in this context, unavoidable side reactions. Keywords: diastereoselectivity; glycosylation; regioselectivity; Introduction The disaccharide α-D-GalpNAc-(1-3)-β-D-GalpNAc is a widespread motif in glycobiology

• desired disaccharide 17, was obtained. Comparing the “normal procedure” with the “inverse procedure” [50], i.e., slow addition of donor 15 to acceptor 9 and catalyst, no discernable difference in the 3/4-O-regioselectivity or the α/β-ratio was observed, albeit a slightly lower isolated yield was obtained

• -protective groups, a 4-O-protective group should be avoided, i.e., use the diol acceptor. Bulky 6-O-protective groups on the donor enhance the α-selectivity. Bulky 6-O-protective groups on either the donor or the acceptor enhance the 3-O-regioselectivity. This simplification in synthesis allows for easier

Copolymerization of epoxides with cyclic anhydrides catalyzed by dinuclear cobalt complexes

• Yo Hiranoi and
• Koji Nakano

Beilstein J. Org. Chem. 2018, 14, 2779–2788, doi:10.3762/bjoc.14.255

• metal-catalyzed PO/PA copolymerization [41]. As there were no detectable signal for ether linkages in the 1H NMR spectra of the obtained copolymers, the resulting copolymers possess a completely alternating structure. The regioselectivity in the ring-opening of PO was estimated by analyzing the

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

• intermediate 3-nitro-2H-chromenes with organic azides in a one-pot two-step sequence. The triazolochromenes were formed with complete regioselectivity and new biologically relevant structures were synthesized via extension of the developed procedure and via postfunctionalization. The mechanochemical synthesis

• regioselectivity in the formation of triazolochromene 5a via 3-nitro-2H-chromene (3). Next, the two-step synthesis was converted into a one-pot two-step synthesis, circumventing the need for isolating the intermediate 3-nitro-2H-chromene (3), which would greatly facilitate the purification of the overall reaction

• triethylamine was needed but the overall yield of 5a was still lower as it only reached 38%. With the obtained optimized conditions and proof of regioselectivity in hand, further investigation towards the generality of this three-component reaction was carried out by varying the substrate scope (Figure 1). We

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• condensation step more difficult. The regioselectivity of the reactions with monosubstituted hydrazines is controlled by the higher reactivity of the ketone moiety over the ester towards nucleophiles, and the least hindered terminal nitrogen atom of the binucleophiles. Both reactions were repeated in AcOH

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• 8-positions would require a different strategy due to regioselectivity issues encountered in the Grignard acylation step (5b→4b). As part of an ongoing research program investigating new assays toward integrase inhibition, we desired to synthesize quinoline derivatives such as 2 with substitution in

• regioselectivity issues and practical challenges associated with the aniline cyclocondensation (7→8), along with the scarcity of commercially available highly substituted quinolines, we sought to employ an entirely different tactic by utilizing 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride) chemistry [16][17

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

• yields. The reaction successfully proceeded even with unsymmetrical internal alkynes. For instance, 1-(1-naphthyl)-1-hexyne (16c) afforded 17c-D in 82% yield with excellent regioselectivity (Scheme 16). Thienyl-substituted alkynes such as 16d and 16e selectively furnished 17d-D, 17d-Allyl, and 17e-D

• 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

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• ). Pleasingly, acetanilides with both electron-donating (1b–d) and electron-withdrawing substituents (1e–g) could be converted in yields of between 39-67%. The lower yields of some of these conversions highlight the challenging nature of this coupling. Thereafter, regioselectivity was studied by the inclusion

• of a range of meta-substituted acetanilides (1h–m). In most cases the products were obtained in a regioselective manner with substitution at the least hindered C–H bond. This regioselectivity has been observed previously in Cp*Co(III)-catalysis using benzamides as substrates by ourselves and others

• product (for the spectra see Supporting Information File 1). The exact regioselectivity of the major product was confirmed through the correlation between the carbonyl C atom and the single ortho-hydrogen atom on the newly substituted aromatic ring (see Supporting Information File 1 for all correlation

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• at the less-hindered carbon of the unsymmetrical alkynes, which causes the high regioselectivity. Later, they proved that the hydroarylation reaction was also feasible with benzoxazoles 5 to form alkenated products 6 using CoBr2, bis[(2-diphenylphosphino)phenyl] ether (DPEphos), Grignard reagent, and

• amines, and silyl alkynes in the presence of CoCp*(CO)I2 catalyst gave uncommon branched-selective products 16 in good yields with reasonable selectivity (Scheme 12) [56]. DFT calculations indicated that the regioselectivity of silyl alkynes was controlled by its steric effect in the protonolysis step

• , whereas the IPr·HCl ligand provided tetrahydropyridoindoles 31 in reasonable regioselectivity (Scheme 22) [70]. Remarkably, the regioselectivity of the reaction is not only controlled by the steric effect of NHC ligand, but also depends on the olefin tether in 29. Recently, Petit and co-workers also

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

• unactivated alkenes (H–X addition, X = H, F, Cl, Br, I, O, S, Se, N, and C). We have also reported the first reductive coupling reactions of alkenes and aryldiazonium salts under HAT conditions. These transformations proceed in high regioselectivity and efficiency. Further efforts will focus on expanding the