From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• .12.264 Abstract The mesomeric betaine imidazolium-1-ylphenolate forms a borane adduct with tris(pentafluorophenyl)borane by coordination with the phenolate oxygen, whereas its NHC tautomer 1-(2-phenol)imidazol-2-ylidene reacts with (triphenylphosphine)gold(I) chloride to give the cationic NHC complex [Au

• tautomer; imidazol-2-ylidene; mesoionic compound; mesomeric betaine; Introduction Since the first isolation of a stable N-heterocyclic carbene (NHC) [1] in 1991 this compound class has provided numerous highly efficient ligands of NHC-metal catalysts for cross-coupling reactions [2][3][4][5][6][7

• tautomer under these conditions; unfortunately the addition of less polar solvents induces a precipitation from solution so that detection of the NHC tautomer by NMR spectroscopy is not possible under these conditions. Base screening revealed that the anionic N-heterocyclic carbene 7 can be generated in

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• between acetamide (AA) as a Gln166 side-chain mimic and tautomers of bases with sp3 (8a) vs sp2 (8b and 8c) hybridized N-1 nitrogen atoms (Table 1; for details, see Supporting Information File 1, Table S4). The uracil/AA tautomer with the sp3 hybridized N-1 atom is thermodynamically more stable by 9 and

• of α-D-PF-1P. Among the bases analyzed, only the sp2 N-1 form of the 4-thiouracil/AA structure 8b is thermodynamically favorable over the N-1 sp3 tautomer 8a by −6 kcal/mol and the partial charge of the N-1 is calculated to be −0.166 e, which is compatible with its satisfactory substrate activity for

• -anionic form of the tautomer 6 of 4-thiouracil [48][49] (Figure 3). Decrease in the rate of the transglycosylation reaction of 4-thiouracil vs uracil can be explained by the decrease of the hydrogen binding capacity of C-4 sulfur atom compared with the oxygen (cf. the corresponding data for uracil and 4

Thiazol-4-one derivatives from the reaction of monosubstituted thioureas with maleimides: structures and factors determining the selectivity and tautomeric equilibrium in solution

• Alena S. Pankova,
• Pavel R. Golubev,
• Alexander F. Khlebnikov,
• Alexander Yu. Ivanov and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2016, 12, 2563–2569, doi:10.3762/bjoc.12.251

• tautomers, except for the case of a strong electron-withdrawing group which changes the ratio in favor of the imino tautomer. The amino form prevails for alkyl-substituted thiazolidines. Reactions of N-methyl- and N-ethylthioureas depend on the solvent and temperature. The best regioselectivity can be

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• . Deuterium labeling experiments have shown that the hydrogenation reaction occurs only on the chiral keto tautomer, and therefore the catalyst selects one enantiomer of the substrate when the reduction takes place. Enantioconvergent methods are not limited to carbon stereocenters. An exceptional example of

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• , starting with the formation of the previously mentioned intermediate 8, followed by hydrolysis of its imino tautomer to give 14 and a final oxidation by perchloric acid. One of the proposed intermediates (compound 14b) was isolated by lowering the amount of perchloric acid, and was transformed into 11b

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• enol tautomer (see Supporting Information File 1). Indeed, perusal of the literature indicated that apparently all 4-monosubstituted 2,3-pyrrolidinediones are highly enolized [13][14][15]. Protection of the enolic OH with a benzyl group, using BnBr and K2CO3, gave compound 4. The reduction of 4 with

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• not be distinguished. Therefore, a synthetic peptide substrate was tested with recombinant TclM [82]. This showed that standalone TclM does function as a “hetero-Diels–Alderase” and a potential concerted mechanism has been proposed that involves the imidic acid tautomer of one amino acid residue

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• oligomeric side products. The resulting primary condensation products contain a 4-hydroxy group in the newly formed pyridine ring that also exists as 4-pyridone tautomer making the identification and purification at this stage inconvenient. We therefore removed all volatile components from the crude products

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• . entries 3 and 5) stabilize carbene tautomer 3 slightly. Changing N-alkyl for N-aryl substituents in the imidazolium ring has a relatively small effect on the tautomeric ratio (Table 3, entries 1 and 3). At the same time, the solvent has a dramatic effect on the equilibrium position. In the gas phase

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• detected with IC50 values in the range of 8–15 μM, a concentration comparable to that of curcumin [13]. It is generally acknowledged that aryl β-diketoester moiety enolizes in the α-position to form the resultant stable Z-enol tautomer. The presence of a carbonyl function in conjugation with the enolic

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• activation of the terminal alkyne moiety of the substrate with AgOTf to generate the Ag–alkyne π complex I (or its tautomer II). Subsequently, the Ag–alkyne π complex I or II is converted into complex III through a nucleophilic attack of the nitrogen atom of the amide, and then produces the final product

Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF

• Erdal Ertas,
• İlknur Demirtas and
• Turan Ozturk

Beilstein J. Org. Chem. 2015, 11, 403–415, doi:10.3762/bjoc.11.46

• 15 (refluxing toluene) initially leading to the formation of enethiols 8, a tautomer of 7, then nine-membered ring 9, rearrangement of which produces 10. Lastly, the reaction of 10 with fragment 14 of LR would give 11 as a major product (Scheme 1). Rearrangement of the 1,4-dithiin unit of 11 would

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• acetaldehyde completes the catalytic cycle. The 4’-aminopyrimidine ring of ThDP can interconvert among three ionization/tautomeric states, the protonated form and two neutral forms, the amino tautomer and the imino tautomer (Scheme 1) and it is believed to be the imine nitrogen atom of the latter that is the

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• exploits the ability of a minor tautomer of B to mismatch with standard T (Figure 3), After this initial mismatch, the misincorporated T directs the incorporation of dATP, resulting in a net conversion of the S:B pairs in the preliminary construct to T:A pairs in the final construct (Figure 3) [20]. This

• conversion of the AEGIS-containing L-DNA product “Conversion PCR” [25][26] of the assembled product was then carried out using Taq Full DNA polymerase (Clontech), which lacks proofreading ability. This leads to the replacement of S:B pairs by T:A pairs, presumably via the “minor enol tautomer” mechanism

• cycles. In the first, dBTP is incorporated opposite template dS, while dTTP is mismatched opposite template dB, presumably via its minor tautomer. In the second cycle, conversion is completed by mismatching dT opposite the minor enol dB in the newly synthesized template (Figure 3). Thus, the use of dBTP

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• thionucleobases is characteristic for their thio–keto tautomer [52]. This band is shifted towards shorter wavelengths upon alkylation at the sulfur atom and loss of the carbon–sulfur double bond. A small fraction of single-stranded ODN with low 332 nm absorption remains and can be assigned to alkylation products

(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• -Phenylpropionyl)-1-indanone (3a): Obtained from β-phenylpropionic acid (1a, 150 mg, 1 mmol), TFAA (0.85 mL, 6 mmol) and TfOH (44 μL, 0.5 mmol) in 75% (100 mg) yield as a red solid. Mp 65–66 °C (Lit. [29]: mp 68–69 °C); 1H NMR (400 MHz, CDCl3) keto-enol (20:80); enol tautomer: δ 7.80 (d, J = 7.6 MHz, HAr, 1H

• °C; 1H NMR (400 MHz, CDCl3) keto-enol (2:98), enol tautomer: δ 7.81 (d, J = 7.6 Hz, HAr, 1H), 7.52 (t, J = 7.4 Hz, HAr, 1H), 7.46 (d, J = 7.5 Hz, HAr, 1H), 7.38 (t, J = 7.4 Hz, HAr, 1H), 3.58 (s, CH2Ind, 2H), 2.18 (s, CH2Ad, 2H), 1.98 (bs, CHAd, 3H,), 1.75–1.59 (m, CH2Ad, 12H); 13С NMR (100 MHz

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• a strand containing B is copied by a polymerase that is not given any dSTP, mismatching of T opposite a minor enol tautomer of B leads (after two cycles of copying) to the replacements of S:B pairs by T:A pairs. (bottom) The conversion of Z:P pairs to C:G pairs involves the mismatching of C opposite

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• (TDA, 1a) is an antibiotic produced by the marine bacterium Phaeobacter inhibens. It has an unusual structure that is made up by a dithiet moiety fused to tropone-2-carboxylic acid (Figure 1) [1]. In Phaeobacter the compound is accompanied by hydroxy-TDA 2, while its tautomer thiotropocin (1b) was

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• main tautomers is shifted to the N-7 sp2-hybridized tautomer, which will be protonated and gives rise to (i) the hydrogen bond connected base, and (ii) the N-9 sp2-hybridized tautomers 14 and 15 in the transition state, which are reacting with the electrophilic C-1 atom of the 1-O-phosphate 12a (Scheme

• possibility for the correct binding at the catalytic site of PNP. On the other hand, the 17a 17b equilibrium, which is slightly biased toward the N-9 sp3 tautomer 17a (Figure 7) and the high partial charge of the nucleophilic sp2 hybridized N-9 nitrogen atom of the tautomer 17b may be responsible for the

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• role. The corresponding ethyl ester 5c exhibits the same characteristics as its methyl congener 5b. As found with 5c dominance of tautomer 5cA1 can also be deduced from an inspection of the 13C NMR spectrum in DMSO-d6 solution. In Supporting Information File 1, Tables S6 and S7 signals for compounds 5a

• corrections E(DFT) and relative energies of tautomers ΔE(DFT) of studied compounds are summarized in Supporting Information File 1, Tables S8–S11. The most stable structural form in the 5a series is the 5aA1 tautomer (56% in ethanol) closely followed by the 5aA2 tautomer (44% in ethanol), which is less stable

• in both ethanol and DMSO by only 0.6 and 0.4 kJ·mol−1, respectively. The remaining tautomers are probably absent in solution because their energies are more than 85 kJ·mol−1 higher than the 5aA1 tautomer in both solutions (Supporting Information File 1, Table S8). This is in agreement with

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• tautomerizes, the authors proposed a plausible mechanism, in which tautomer 113 undergoes cyclization via an intramolecular Michael reaction to give intermediate 114. The next step involves cleavage of the dimethylamine group to afford the thiazole structures 115. In 2003, the same group also described a solid

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• of 14a (ca. 1:1 ratio of its epimers) forms an equilibrium with its ketone tautomer in a 1.8:1 ratio. In contrast to hydroxyketones 7a–d the furan tautomer of 14a is thermodynamically more stable than the keto form. This might be rationalized by a lower steric strain in the heterocyclic form due to

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• form the indolizidinone ring. Thus, ozonolysis of olefin 22 in dichloromethane [51], followed by quenching with Me2S furnished the hemiaminal tautomer via intermediacy of lactam-aldehyde. Without isolation, the crude was subjected to the reductive dehydroxylation with Et3SiH/BF3·Et2O (CH2Cl2, −78 °C