Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• enzymatic step [1][2][3]. With this approach, nature makes perfect use of the versatile chemistry of carbocations with its hydride or proton shifts and Wagner–Meerwein rearrangements leading to a large variety of possible structures. Among terpenoid natural products, achiral compounds are rarely found, but

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• from 2’-chloroacetophenone as the starting material through treatment with carbon disulfide in the presence of sodium hydride [23], followed by alkylation using iodoethane according to the literature procedures [13][16][17][19]. The oxidation of 1 with 1.2 or 5 equiv of H2O2 yielded ethyl sulfoxide 2

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

• purified and characterized or, for further transformations, the crude products are directly converted into the corresponding nonaflates by deprotonation with sodium hydride and treatment with 1-nonafluorobutanesulfonyl fluoride (NfF). Scheme 13 shows two examples, PM52 and PM54 that are ready for palladium

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• by hydride abstraction from (Ar1Ar1Ar2)CH are also demonstrated. Results and Discussion At the onset a series of non-commercial N-alkylindoles 1{4–10} and quinoline-/quinolone aldehydes 6{1-7} were prepared (Scheme 3 and Scheme 4). The N-methyl-, N-butyl- and N-benzylindoles 1{4–10} were synthesized

• attempts to cleanly generate the salts by hydride abstraction with trityl-BF4 were unsuccessful [61], presumably due to extreme steric crowding, the reaction with DDQ/HPF6 (Scheme 8) [62][63][64][65] was successful and the methylium-PF6 salts 10{4,4,8} and 10{4,4,11}, respectively, precipitated from DCM as

• despite significant steric crowding. Steric congestion restricts the conjugation of the carbocationic center with the aromatic/heteroaromatic substituents, as evidenced by the bond length shortenings from only 0.052 Å to 0.111 Å observed upon hydride abstraction. The optimized geometries confirm the

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

• and a connection to a combined nitrogen-vacuum line, charged with sodium hydride (1.6 g; 60% in mineral oil, 40 mmol) and closed with a septum. n-Hexane (20 mL) was injected by syringe and the suspension was stirred for 10 min. Then, stirring was interrupted and the supernatant liquid was removed by

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• phthalimides 16 and 23 [29]. These intermediary compounds 16 and 23 also allowed an N-methylation of the azaindole moiety with sodium hydride (NaH) and methyl iodide (MeI) to yield 17 and 24. By ethanolic hydrazinolysis and microwave irradiation the phthalimides (16, 17, 23, and 24) were deprotected yielding

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• . Water can lead to the formation of catalytically inactive Ru hydride species. Fürstner et al. isolated these complexes as byproducts during the synthesis of Grubbs second generation-type catalysts with saturated NHC ligands [29]. In this specific case, the formation of the metal hydride complex is

• water is more likely to occur at high temperatures and in the presence of a base. 1H NMR studies revealed that methanol is the source of hydride and this was later confirmed by Grubbs and co-workers [31]. The proposed mechanism for the degradation of G-I occurs via alcohol dehydrogenation followed by

• decarbonylation of the ruthenium hydride 16. In 2015, Cazin and co-workers showed that the detrimental effect of H2O also occurs with the more innovative catalysts Caz-I, Ind-II and HG-II (Table 1) [32]. The authors performed the RCM of the challenging substrate 17 in toluene at 110 °C, reporting excellent yields

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• -4,6-O-benzylidene-β-D-glucopyranoside (9). Compound 9 was treated with benzyl bromide in the presence of sodium hydride [20] to give O-benzylated derivative 10 in 90% yield in two steps, which on de-O-allylation by treatment with palladium chloride [21] furnished 2-azidoethyl 2-O-benzyl-4,6-O

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

• ]. Many of these complexes contain rhodium or iridium coordinated with fully (methyl)substituted cyclopentadienyl ligands and bis-coordinating diamino ligands as shown in Figure 7. The reducing agent may be a formate anion as a source of hydride, triethanolamine as an electron donor in the case of

• photoactivated reduction, or hydrogen gas under atmospheric pressure. Some of these complexes were used in the successful electrochemical regeneration of NAD(P)H [83]. According to the proposed mechanism of the complex-catalyzed reduction [75], reaction of a complex with, for example, formate generates a hydride

• metal complex. The amide functionality in the 3-nicotinamide core plays a crucial role in the subsequent reduction because it coordinates with the metal center of the hydride complex, resulting in a favorable transition state which ensures the transfer of the hydride on the 4-C position of the

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• standard syringe–septum techniques. All purchased solvents (CH2Cl2, THF, acetonitrile, and DMF) were dried over calcium hydride (CaH2) or sodium. Column chromatography was performed by using Acme’s silica gel (100–200 mesh) with an appropriate mixture of ethyl acetate, petroleum ether methanol and

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• hydrogenation of double bonds, especially for long reaction times. The ability of the Gr2 catalyst to form Ru–hydride complexes in the presence of alcohols is well-known and described in the literature [98][99]. Such complexes promoting C=C bond hydrogenation were detected in the PNB–PCOE(OH)–Gr2 system using

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• an increase in IPs) indicates decomposition of the precatalyst to active isomerisation species, probably metal hydride species. In our NMR study no indication of the existence of metal hydride species was found. Conclusion The aim of our research is to control the Ru–N bond strength of the bidentate

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• previous study was 3 MPa [27], 5 MPa CO2 was applied in the present study to promote a higher consumption of LO. The result showed the isolated yields were improved to 84% yield for 1a and 30% yield for 1d. In our previous report, 1d was reduced by lithium aluminium hydride (LAH) to obtain the

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• the presence of persilylated thymine to produce the iodine intermediates 2α/β (Scheme 1, Table 1, entry 1). These instable intermediates were then directly reduced with tributyltin hydride (Bu3SnH) to yield the tricyclic nucleosides 5α/β as main compounds. However, we observed the occurrence of the

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• recently showed that 3-alkoxy-substituted N-acylpyrazinium salts can be selectively reduced by tributyltin hydride to afford 1,2-dihydropyrazines in good to excellent yields [9]. There have been other reports involving the addition of TMS-ketene acetals to pyrazinium salts [10][11][12]. A double

• , Table 1). Changing the solvent to diethyl ether showed no improvement in the yield of 3a but when THF was used, an excellent yield of 87% was produced (entries 4 and 5, Table 1). Based on our previously developed selective tin hydride reduction of monosubstituted pyrazinium salts [9], we expected the

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

• solution [38] (run 2 in Table 1) and with Me2SO4 and K2CO3 in 0.023 M solution [39] (run 3 in Table 1) afforded 1 in 86% and 72% yields, respectively. In the remaining reaction the use of sodium hydride (NaH) as a base produced 1 in 84% yield [40] (run 4 in Table 1). We at first re-examined these reactions

A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety

• Ilya V. Taydakov,
• Yuliya M. Kreshchenova and
• Ekaterina P. Dolotova

Beilstein J. Org. Chem. 2018, 14, 3106–3111, doi:10.3762/bjoc.14.290

• dispersion in native form [18][19][25], we have found that mineral oil should be removed before the synthesis. The results of the optimization experiments are summarized in Table 1. The safest way to remove oil is by washing sodium hydride by means of decantation directly in the reaction flask. This

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• persilylated thymine in the presence of NIS (Scheme 2), followed by radical reduction of the iodide intermediate with tributyltin hydride (Bu3SnH) generated an anomeric mixture of nucleoside 6α/β with the β-anomer as major component (α/β ratio = 1:4.5 according to 1H NMR). The inseparable anomers of nucleoside

• the nucleobase was conducted by 1H,1H-ROESY experiments (Supporting Information File 1). The β-anomer 7β then was subjected to Luche reduction [55][56] producing selectively the desired S-configuration at the C(5’) position due to hydride delivery from the less hindered exo-side of the carbonyl group

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• preponderant product) may be encountered when the deprotonating base is added to the alcohol 13 either too slowly or in a less than stoichiometric amount. For instance (bottom line of Scheme 3), the heterogeneous, slow deprotonation of 13 in THF by the insoluble base potassium hydride (KH) afforded 11 and 1 as

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

• catalyst A in dichloromethane at ambient temperature, higher dilution and after prolonged reaction time. For the synthesis of furanocoumarins 3 the allyl ethers 9 were first subjected to a Ru hydride-catalyzed double bond isomerization [55][56] to furnish enol ethers 10 as inseparable mixtures of

• subjected to the isomerization conditions previously used for the synthesis of furanocoumarin precursors 10 (see Table 2) we observed no conversion. A plausible explanation is the formation of a stable six-membered Ru–O–chelate complex following hydroruthenation, which inhibits a subsequent β-hydride

• elimination and thus interrupts the catalytic cycle. For these reasons we started from the MOM-protected 8-allylcoumarins 7, which underwent the Ru-hydride catalyzed double bond migration smoothly. The MOM group was cleaved off without isolation of the intermediate products and the required 7-hydroxy-8-(prop

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• obtained for the desired products due to the formation of substantial amounts of ring-opened byproducts 10 resulting from the hydride addition to the carbonyl group of the oxazolidinone ring [33][34]. The alcohols 9 were then subjected to a Swern oxidation followed by a Wittig reaction to generate the

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• -amino esters, we tried their preparation via a C-methylation of α-nitroester 6a in DMF using sodium hydride and methyl iodide. Upon purification, this gave 46% of the nitro compound 9 with 94% purity (as assessed by 1H NMR). Despite this modest yield, the ensuing reduction using zinc and hydrochloric

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

• introduced by Sinaÿ et al. [10] and continued in the studies by Sollogoub et al. [11][12]. The addition of diisobutylaluminum hydride (DIBAL-H) to perbenzylated CDs exclusively formed a single AD regioisomer on the primary rim of α-CD. Conversely, the direct, straightforward modification is mostly performed

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• replacement of carbon atoms by the heteroatoms oxygen, nitrogen and sulfur, respectively. Thus, “oxacarbenium ion” would denote a carbenium ion whose carbon atom is replaced by an oxygen atom, that is, an oxonium ion (3; Figure 2). Although if a coherent structure by formal subtraction of hydride from the

• ” (divalent carbon atom bound to a parent hydride) and “oxonium ion” (or “oxidanium ion”) forming “carbenoxonium ions” (or “carbenoxidanium ions”). These other terms are as long as the names currently used in the literature commented above, but they lack the stem of the functional group they come from and

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

• synthesis method through the one-pot acylation of ethyl acetoacetate with isatoic anhydrides followed by dehydrative intramolecular cyclization to access the desired quinoline scaffold 10 [18]. We replaced sodium hydride as the base required to generate the enolate of ethyl acetoacetate with sodium

• hydroxide [19][20]. The use of sodium hydride is of particular concern upon reaction scale-up due to limited solubility in organic solvents and the production of flammable hydrogen gas [21][22]. Sodium hydroxide avoids the off-gassing of hydrogen and produces water instead, thereby avoiding the use of any

• intramolecular 6-exo-trig cyclization and subsequent proton transfer to the aminal oxygen D. Elimination of the 2-hydroxy group from D then affords the 4-quinolone E that tautomerizes via [1,5]-hydride shift to form quinoline 10. Given the success of employing ethyl acetoacetate in the quinoline