The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrroles as minor products via further rearrangement. Keywords: 1,4-dihydropyridine; electron-withdrawing alkyne; formal [2 + 2] cycloaddition; Huisgen's 1,4-dipole; isoquinoline

• Povarov reaction of 3-aminocoumarins, aldehydes, and 5,6-unsubstituted 1,4-dihydropyridine derivatives for the construction of exo-hexahydrochromeno[3,4-h][1,6]naphthyridine-3-carboxylate derivatives (reaction 3 in Scheme 1) [44]. In these reactions, the 5,6-unsubstituted 1,4-dihydropyridines usually

• ]naphthyridine and 2-azabicyclo[4.2.0]octa-3,7-diene derivatives. Results and Discussion Initially, the reaction conditions were briefly examined by using isoquinoline (1), dimethyl acetylenedicarboxylate (DMAD, 2) and 5,6-unsubstituted 1,4-dihydropyridine 3 as standard reaction (Table 1). The three-component

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

• -aryl-, 2-aryl-6-aryl and 2,6-diaryl-5-aryl/hetaryl-substituted methyl 4-oxo-1,4-dihydropyridine-3-carboxylates by Mo(CO)6-mediated ring expansion of methyl 2-(isoxazol-5-yl)-3-oxopropanoates. The high reactivity of 4-oxo-1,4-dihydropyridine-3-carboxylates synthesized provide easy access to 2,4,6

• represented among drugs [5][6][7][8][9][10][11][12]. Some of bioactive compounds, such as ciprofloxacin, levofloxacin, delafloxacin, and elvitegravir, contain the fragment of 4-oxo-1,4-dihydropyridine-3-carboxylic acid [6][8] and some others, ivacaftor, dolutegravir, bictegravir, aspernigrin B, and 4PYR

• , contain the fragment of 4-oxo-1,4-dihydropyridine-3-carboxamide [5][6][7]. Finding new synthetic methods for the preparation of derivatives of 4-oxo-1,4-dihydropyridine-3-carboxylic acid are therefore relevant. Some alkyl 6-aryl-2-methyl-4-oxo-1,4-dihydropyridine-3-carboxylates were prepared by refluxing

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• , we synthesized a Ni–chitosan complex and exploited the coordination properties of the complex to use it as an effective and recyclable catalyst towards the green synthesis of C5–C6-unsubstituted 1,4-dihydropyridine (1,4-DHP) scaffolds. Ultrasonic irradiation is an important technique in the toolbox

• vacuum at 60 °C. The synthesized pure Ni–chitosan nanocatalyst was characterized by powder FTIR and XRD spectroscopy, TEM, FESEM, and EDX analysis. Preparation of 1,4-dihydropyridine-2,3-dicarboxylate derivatives A primary amine 1 (1 mmol), a dialkyl but-2-ynedioate 2 (1 mmol), a cinnamaldehyde 3 (1 mmol

• NPs. EDX spectrum of the Ni–chitosan NPs. Synthesis of dialkyl 1,4-dihydropyridine-2,3-dicarboxylate derivatives. ORTEP representation of product 4a (CCDC 1949329). Recycling experiment of the Ni–chitosan nanocatalyst. A plausible mechanistic route for the synthesis of C5–C6-unsubstituted 1,4-DHP

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• quinolones 56, indolo[3,2-c]quinolines 57, β-amino acids 58, and 1,4-dihydropyridine derivatives 59 were obtained through this route in moderate yields (Scheme 26). Besides nucleophiles, aromatic amines also reacted with redox-active radical precursors, such as NHPI [95] and N-alkoxyphthalimides 55 [96]. The

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• ). Methyl 4-pyridylacetate 11 also gave the corresponding trifluoromethylthiolated product 12 in 29% yield (Scheme 6), where the reaction was assumed to proceed via the N-trifluoromethylthio-4-alkylidene-1,4-dihydropyridine intermediate. In contrast, methyl 3-pyridylacetate 13 did not yield the

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• 4CzIPN (OD6), due to its oxidative abilities in the excited state (E(PC*/PC−) ≈ 1.35 V), has proved to be a versatile organic photocatalyst for accessing C(sp3) radicals through oxidative fragmentations. In particular, it has been used for generating an alkyl radical from the 4-alkyl-1,4-dihydropyridine

• responsible for the H atom abstraction from the α-keto acid. The α-keto carboxyl radical undergoes a decarboxylation, leading to the desired acyl radical. Acyl radicals can also be accessed through the oxidative cleavage of a redox-active group, such as acylsilanes or 1,4-dihydropyridine derivatives. In 2018

• acceptors 18.2 to afford the desired ketone 18.3. Recently, the Melchiorre group reported a carbamoyl radical-mediated metallaphotoredox synthesis of arylamides (Scheme 19) [91]. In this protocol, excited-state 4CzIPN (OD6) oxidizes a 4-carbamoyl-1,4-dihydropyridine 19.1, which then fragments, releasing the

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• the 1,4-dihydropyridine scaffold. As depicted in Scheme 14, compound 46 was later subjected to a variety of post-MCR cyclizations, including the reaction with carboxylic acids to form the fused steroidal pyridopyrimidinones 47 and with carbon disulfide to form pyridopyrimidinedithione 48 in very good

• androstanic steroids. Such heterocyclic moieties are of interest because of their pharmacological activity, for example, as anti-inflammatory agents. Employing epiandrosterone and benzaldehyde as oxo components, ammonium acetate and malononitrile as C-nucleophile, the authors produced 2-amino-3-cyano-1,4

• -dihydropyridine 46 fused to the androstane at positions 16 and 17 (Scheme 14). The MCR proceeds by the condensation of malononitrile with benzaldehyde to form the benzylidene malononitrile adduct, and of the ketosteroid with ammonium to form the steroidal enamine, which cyclizes with the benzylidene to furnish

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

• of substituents R1, R2, R3, and R4 [67][68][69]. For instance, in the case of starting substrate H, in which R1, R3, R4 = Me and R2 = CN, the reduced product contained 70% of 1,2-dihydropyridine and 30% of 1,4-dihydropyridine as established by NMR spectral analysis. Reduction of N1-methyl-3

• hexachloroacetone [28][71] or cobalt(II) acetate in the presence of hydrogen peroxide followed by removal of the cobalt cations with QuadraSil AP resin [60]. The nature of the counter anion vary as a function of the conditions applied. Reduction of N1-substituted 3-nicotinamide salts to the corresponding 1,4

• -dihydropyridine derivatives may be also accomplished by using catalysis with organometallic complexes [72][73][74][75][76][77][78][79] or platinum nanoparticles [80]. This recently developed approach stems from an independent field of research, which focuses on the regeneration of NAD(P)H from NAD(P)+ [81][82

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• reactions proceed in the absence of any added base emphasizing the highly electrophilic character of ANBF. The resulting compounds combine in one molecule NO-donor furoxan ring along with a pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for

• ring along with the pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for the design of pharmacology-oriented heterocyclic systems. General view of molecule 12 in crystal. Anisotropic displacement parameters for non-hydrogen atoms are

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• cyanoacetate) with triethylamine as base catalyst afforded functionalized 1-benzamidospiro[indoline-3,4'-pyridines] in good yields. 1H NMR spectra indicated that an equilibrium of cis/trans-conformations exist in the obtained products. Keywords: acetylenedicarboxylate; benzohydrazide; 1,4-dihydropyridine

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• corresponding enamine as compared to the activation of the sugar aldehyde. The preliminary studies of the Dondoni group on the synthesis of C-nucleosides bearing the unsymmetrical 1,4-dihydropyridine nucleobase showed that the internal asymmetric induction by the sugar moiety played a crucial role in the

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• and sets the stage for their future incorporation into automated multistep processes. Experimental Diethyl 4-(trimethylsilylethynyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (15d) 3-Component Hantzsch DHP synthesis in a single-mode microwave batch reactor (Table 3, entry 5). A mixture of 3

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• arylamines and other primary amines. Keywords: 1,4-dihydropyridine; electron-deficient alkyne; four-component reaction; isatin; one-pot reaction; spiro compound; Introduction β-Enaminones and β-enamino esters represent important synthetic building blocks for the development of versatile carbon–carbon bond

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

• might therefore be possible, provided that the overall reaction rate is not too slow. To further test this hypothesis, N-allyl-ynamide 1a was reacted under similar reaction conditions and to our delight, a smooth cyclization occurred, the expected 1,4-dihydropyridine 5a being virtually formed as

• starting N-allyl-ynamides. Intramolecular carbolithiation of N-allyl-ynamides to 1,4-dihydropyridines and pyridines. 2,3-Disubstituted pyridines by trapping of the intermediate metallated 1,4-dihydropyridine. Formal synthesis of the anti-dyskinesia agent, 5-HT1A receptor agonist, dopamine D2 receptor

• , conditions A) or acetic acid and o-chloranil (Scheme 4, conditions B), yielding the corresponding 1,4-dihydropyridines 5 or pyridines 6, respectively. Results from these studies are collected in Scheme 4, yields being indicated only in the pyridine series due to the high sensitivity of the 1,4

Enaminones in a multicomponent synthesis of 4-aryldihydropyridines for potential applications in photoinduced intramolecular electron-transfer systems

• Nouria A. Al-Awadi,
• Maher R. Ibrahim,
• Mohamed H. Elnagdi,
• Elizabeth John and
• Yehia A. Ibrahim

Beilstein J. Org. Chem. 2012, 8, 441–447, doi:10.3762/bjoc.8.50

• , enamino ester 11 and enaminonitrile 13. Thus, 1,4-dihydropyridine-3,5-dicarboxaldehyde 10a,b, 1,4-dihydropyridine-3,5-dicarboxylate 12 and 1,4-dihydropyridine-3,5-dicarbonitrile 14 were successfully obtained by reacting β-N,N-dimethylaminoacrolein (9), ethyl β-N,N-dimethylaminoacrylate (11) or β

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• number of potential hypotensive agents containing SRF and SO2RF groups of the 1,4-dihydropyridine class and also of Losartan (Dup 753) analogues which are used clinically for the treatment of cardiovascular diseases have also been developed [5][6] (Figure 3). Other patented compounds containing