Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• Scheme 2. It is similar to that of HOTf-catalyzed intramolecular sulfonamide hydroamination (−34 ± 5 cal/mol·K) [31] and different from that measured for intramolecular pyridone hydroamination (−6.2 ± 0.8 cal/mol·K) [11]. Isotope effects. The presence or absence of kinetic deuterium isotope effect is

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• ratio of pyridinic and pyridone nitrogen being 68% and 29%, respectively, compared to 62% and 38% in g-h-PCN (Figure 2e). Phosphorus 2p focused scans of g-h-PCN300 showed a slight reduction in P–O and P=O bond character from g-h-PCN to g-h-PCN300 down from 69% to 66% (Figure 2f). Analysis by infrared

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• recognized as challenging since there is no single report on such a sequence under Lewis acid catalysis. Herein, we report the synthesis of phosphoric esters by a Lewis acid Cu(OTf)2-catalyzed one-pot Pudovik reaction–phospha-Brook rearrangement sequence between pyridinyl-substituted aldehyde or pyridone

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• -triaryl-substituted and 1,2,5,6-tetrasubstituted nicotinates. Keywords: isoxazole; methyl nicotinate; molybdenum hexacarbonyl; 4-pyridone; ring expansion; Introduction Pyridine moieties are present in many natural products, drugs, pesticides and industrial materials. Pyridine fragments are used in drugs

• formation of pyridone 5 (route b), is less likely due to the lower electrophilicity of the ester carbon compared to the acyl carbon. To check this, isoxazole 1g was synthesized and reacted with Mo(CO)6 in wet acetonitrile at 60 °C for 2 d to give pyridone 2g in 45% yield. The reaction at 70 °C was completed

• in a day to give pyridone 2g in 74% yield. A further increase in temperature, although it led to a reduction in the reaction time, was accompanied by resinification of the reaction mixture and, as a result, led to a decrease in the yields of pyridone 2g (80 °C, 3 h, 63%; 85 °C, 3 h, 42%). Enamine 6

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in MeCN, the yield could be improved to 32% (Table 1, entry 4). Further screening of other oxidants revealed that NMO was the optimal (Table 1, entries 9–11). When the reaction was conducted in neat in the presence of 2-pyridone, 3a was obtained in 36% yield (Table 1, entry 12). However, significant

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• fluorinated organic compounds attractive in many research areas and therefore fluorinating agents are important. N-F agents have proven useful by virtue of their easy handling. This reagent class includes many types of N-F compounds: perfluoro-N-fluoropiperidine, N-fluoro-2-pyridone, N-fluoro-N

• detected, but N-fluoroimides 2-1 and 2-2 were formed. The stability of these N-F compounds was low, since they decomposed to H2NCO(CF2)nCOOH upon standing with air. 1-3. 1-Fluoro-2-pyridone In 1983, Purrington and co-worker synthesized 1-fluoro-2-pyridone (3-1) as a fluorination agent [24]. When 2

• -(trimethylsiloxy)pyridine was allowed to react with 5% F2 diluted with N2 in a freon solvent at −78 °C, 1-fluoro-2-pyridone was obtained in 63% yield (Scheme 5). The fluorination efficiency of 3-1 was higher than perfluoro-N-fluoropiperidine (1-1) and the yields of reaction with sodium diethyl malonates improved

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• to name type-I Guareschi pyridone synthesis the two-component reaction between a β-aminocarbonyl and a cyanoacetic ester, a reaction first reported in 1893 [34]. It is a classic combination of a Knoevenagel condensation and ester aminolysis typical for many heterocyclic syntheses. The type-II

• amine, affording a 6-aminopyridone, which, after acidic treatment, is turned into the same β,β-disubstituted glutarate formed by hydrolysis of the pyridone from the type-IV Guareschi reaction. This modification of the type-IV Guareschi reaction is the “real” Guareschi–Thorpe reaction, which in many

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• pharmaceuticals and biologically active molecules (116–118) [103]. Similarly, heterocycles having pyridone nucleus are pharmacologically important as they can act as potent anticancer (119), antibacterial (120) and antiviral agents (121, Figure 9) [104][105][106]. Shamsuzzaman and co-workers [107] demonstrated

• first time reported a microwave-assisted four-component domino reaction involving acyclic 1,3-diketones 54, amines 32, diethyl malonate (126) and triethyl orthoformate (111) for the synthesis of substituted pyridone derivatives 127 at 120 °C under catalyst- and solvent-free conditions. The reaction

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• ) [19], N-methyl-2-pyridone 7 (δ 139.5) [20], 2,4-dimethoxy-3-methylquinoline (8, δ 147.0) [21], and 2-methoxypyridine 9 (δ 147.2) [22] supported a 2-quinolone form 1 but not 2-quinolinol 2 (Figure 2, Table 1). The same structure was synthesized from diethyl malonate and aniline (see Supporting

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• promoted the addition of Grignard reagents to N-Cbz-pyridone and N-Cbz-2,3-dihydropyridone Michael acceptors with high enantioselectivity and yield. It is worth mentioning that in copper-catalysed additions of Grignard reagents to N-Cbz-pyridone, the use of a Lewis acid (BF3·OEt2) together with the copper

One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines

• Valeriya G. Melekhina,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Vitaly S. Mityanov,
• Artem N. Fakhrutdinov,
• Arkady A. Dudinov,
• Vasily A. Migulin,
• Yulia V. Nelyubina,
• Elizaveta K. Melnikova and
• Michail M. Krayushkin

Beilstein J. Org. Chem. 2019, 15, 2840–2846, doi:10.3762/bjoc.15.277

• fragments proceeds first, followed by intramolecular cyclization (Scheme 4B). The structure of the 4-chloro-substituted pyrrolopyrimidinone 1e was proven by single crystal X-ray analysis (Figure 1). Despite the unambiguous dominance of the pyridone-based conformation in the solid state of 1e, two tautomers

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• further calculations were carried out for the most stable tautomer. The conformational analysis revealed that the pyridone tautomer (1) is ≈150 kJ/mol lower in energy than the dihydroxy tautomer (1OH). The geometry optimizations showed that the geometry of [12 + Me4Nendo]+ is similar without and with

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• rhodium(III)-catalyzed intermolecular annulation has been established for the preparation of tetrazole-isoquinolone/pyridone hybrids. Several N-acylaminomethyltetrazoles were reacted with arylacetylenes to form the hybrid products in moderate to very good yields. The method relies on the capacity of the

• isoquinolones is very wide and may be extended to the preparation of complex compounds having heterocyclic moieties such as pyridone, furan, thiophene and pyrrole, as well as the corresponding benzo-fused derivatives. The developed procedure is simple, reproducible and does not require inert conditions

• could form isoquinolones and pyridones linked to a tetrazole ring, since such class of hybrid compounds is not described in the literature. Several protocols based on C–H activation or metal-catalyzed cyclizations are known to generate the isoquinolone and pyridone moieties and further assist their post

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• reactions can be linked with Povarov MCRs through the intermediacy of the enamine-containing adducts from the former processes (Scheme 10C) [40]. Many additional combinations arise from the Union concept, such as Bredereck–Passerini [41], pyridone-cyclocondensation/Passerini–Ugi [42], azadiene-keteneimine

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• Nitrogen-containing heteroaromatic compounds have valuable properties in medicinal chemistry, pharmacology and functional materials. Among those, pyridinone, sometimes called pyridone, is a key structural motif of well-known active compounds and natural products (Figure 1) [1]. For example, the 2

• previously reported [13], 5-substituted pyridinone 5m could not be functionalized. Isoquinolone 7n was prepared in 82% yield. The methodology could also be applied to 4-pyridone in a moderate 57% yield for product 7o. Unfortunately, pyrazin-2-one 5p could not be functionalized. Modification of the

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

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

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• , the asymmetric Diels–Alder (D–A) reaction between the N-sulfonamide-3-hydroxy-2-pyridone-based dienes 52 and different dienophile substrates was developed using the bifunctional cis-2-trialkylaminoindanol organocatalyst ent-41 [56]. We show herein the reactivity of this family of dienes with several

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• substances were detectable on the cocoon surface for months during hibernation. Structurally, piericidins consist of a pyridone core attached to polyene side chains of variable size, a structural and physiochemical feature of ubiquinone. Therefore, it is not surprising that piericidins are potent inhibitors

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

• -letter GACTSB DNA alphabet. This was an alternative to the AEGIS nucleotides 2-amino-8-(1’-β-D-2’-deoxyribofuranosyl)imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (trivially named P) and 6-amino-5-nitro-3-(1’-β-D-2’-deoxyribofuranosyl)-2(1H)-pyridone (trivially named Z) (Figure 2), which give a GACTZP six

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

• (trivially named B), 2-amino-8-(1’-β-D-2’-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)one (trivially named P), and 6-amino-5-nitro-3-(1’-β-D-2’-deoxyribofuranosyl)-2(1H)-pyridone (trivially named Z) (Figure 2). In both cases, conversion is facilitated by forcing polymerases to mismatch AEGIS

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• derivatives streptazones B1 (1), B2 (2), C (3), the 4-pyridone derivative streptazone D (4) with a pentadienyl side chain, and streptazolin (5) (Figure 1) [8]. Streptazolin is produced by several streptomycetes [8][9][10][11][12], and is formed biosynthetically by a polyketide mechanism [13]. The respective

An efficient method for the construction of polysubstituted 4-pyridones via self-condensation of β-keto amides mediated by P₂O₅ and catalyzed by zinc bromide

• Liquan Tan,
• Peng Zhou,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2013, 9, 2681–2687, doi:10.3762/bjoc.9.304

• 1a–1k could be easily converted into their corresponding 4-pyridone 2a–2k. All the reactions proceeded smoothly and afforded the desired product in good to excellent isolated yields (72–90%) in 4 h. This transformation appears quite tolerant with respect to the positions of the substituents on the

• In summary, we have established an improved efficient synthetic protocol for the synthesis of 4-pyridone derivatives by a sequence of intermolecular dehydration of β-keto amides in the presence of phosphorus pentoxide (P2O5), 1,3-acyl migration and intramolecular dehydration. Comparing to the similar