Tailor-made synthesis of fully alkylated/arylated nicotinates by FeCl<sub>3</sub>-mediated condensation of enamino esters with enones

Hirai, Sho; Horikawa, Yurie; Asahara, Haruyasu; Nishiwaki, Nagatoshi

doi:10.1039/c7cc00051k

Cited by 40 publications

(22 citation statements)

References 39 publications

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“…In 2017, Nishiwaki et al. have synthesized functionalized pyridines 44 (nicotinates) by the reaction of 2‐alkenals 43 with β‐enamino esters 42 in the presence of FeCl 3 in the combination with microwave irradiation (Scheme ) . In this reaction, acrolein, cinnamaldehyde and crotonaldehyde were used as representatives of α,β‐unsaturated aldehydes.…”

Section: Synthesis Of Pyridinesmentioning

confidence: 99%

α,β‐Unsaturated Aldehydes as C‐Building Blocks in the Synthesis of Pyridines, 1,4‐Dihydropyridines and 1,2‐Dihydropyridines

Вчисло

2019

Asian J Org Chem

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N-heterocycles are ubiquitous structural units in a variety of biologically active compounds, pharmaceutical preparations, and natural complex molecules. Thousands of original scientific papers are published annually on various aspects of the formation of nitrogenous heterocycles and the study of their chemical and biological properties. Among them, the synthesis of pyridines and their dihydrogenated derivatives attracts the attention of chemists, which develop synthetic techniques, including those ones based on α,βunsaturated aldehydes. The minireview summarizes and highlights the recent advancements in the construction of pyridines, 1,2-dihydropyridines, and 1,4-dihydropyridines from transformations of 2-alkenals, covering the publications of the last five years. formation of the arylidene moiety A. Then, the Michael addition of dinitrile 51 at the C=C bond of the molecule A lead to the intermediate B which attaches the proton to give intermediate C. The intramolecular nucleophilic attack of NH 2 -group on cyanocarbon of molecule C followed by aromatization into Scheme 10. Ammonia-based synthesis of 1-(2-meth-yl-6-ferrocenylpyridin-3-yl)ethenone 38. Scheme 11. Synthesis of pyridines 41 using enaminones 39. Scheme 12. Use of enals 43 in FeCl 3 -catalyzed reaction with β-enamino esters 42.these compounds for medicine. In the review, it is shown that the use of α,β-unsaturated aldehydes in the synthesis of 1,2dihydropyridines remains rather limited.The material presented in the review demonstrates the wide possibilities of using α,β-unsaturated aldehydes for the synthesis of six-membered azaheterocycles -pyridines, 1,2-and 1,4-dihydropyridines. The advantages of the discussed methods are available starting materials, simple operational procedures, use of environmentally friendly catalysts. This allows chemist to get structurally diverse products with high yields, to reduce time and energy, to avoid isolation of intermediate compounds and thus increase powerful productivity of reaction. Conflict of InterestThe authors declare no conflict of interest.

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Section: Synthesis Of Pyridinesmentioning

confidence: 99%

α,β‐Unsaturated Aldehydes as C‐Building Blocks in the Synthesis of Pyridines, 1,4‐Dihydropyridines and 1,2‐Dihydropyridines

Вчисло

2019

Asian J Org Chem

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“…Figure depicts several drug molecules that contain a nicotinate scaffold, including dexamethasone isonicotinate (an anti‐inflammatory, anti‐allergic glucocorticoid), morniflumate (an analgesic, antipyretic and anti‐inflammatory agent), flunixin meglumin (a cyclooxygenase inhibitor), vitamin E nicotinate (an antioxidants), nicorandil (a vasodilatory drug), and hepronicate (a hypolipidemic drug) . To date, many of approaches have been successfully developed to produce nicotinate skeletons by employing electron‐deficient β ‐enamino esters ( β ‐EAEs) as the readily accessible C,N ‐dinucleophilic synthons combined with the condensation of 1,3‐dicarbonyl compounds, α,β ‐unsaturated ketones, alkynones, Mannich base hydrochlorides, and IBX‐mediated oxidative annulation of allylic alcohols (Scheme ) . However, most of these methods have been compromised by harsh reaction conditions, stoichiometric halogenated reagents, functionalized starting materials, which could not fulfill the requirements of reagent efficiency.…”

Section: Figurementioning

confidence: 99%

Copper Catalysis for Nicotinate Synthesis through β‐Alkenylation/Cyclization of Saturated Ketones with β‐Enamino Esters

et al. 2017

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The first example of a Cu-catalyzed and 4-OH-TEMPO mediated intermolecular [3 + 3] annulation of saturated ketones with b-enamino esters is reported herein, which was successfully used for the synthesis of versatile nicotinates through sequential b-C(sp 3 )-H bond alkenylation, enaminecarbonyl condensation and aromatization. This protocol tolerates a variety of functional groups, thereby providing a practical and efficient method for the fabrication of 5H-chromeno[4,3-b]pyridin-5one skeletons.

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“…In our previous work, we demonstrated an efficient synthetic method for polysubstituted nicotinates via the condensation of an enamino ester with an α,β‐unsaturated carbonyl compound in the presence of FeCl 3 . This protocol facilitates the introduction of different alkyl/aryl groups at the desired positions of the pyridine framework by simply altering the starting materials.…”

Section: Introductionmentioning

confidence: 99%

Three Step Synthesis of Fully and Differently Arylated Pyridines

et al. 2020

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Condensation of -(2-pyridyl)enamine and α, -unsaturated ketone in the presence of FeCl 3 under air afforded highly substituted pyridines. In this transformation, FeCl 3 acted as not only an acid catalyst but also an oxidant for the intermediate dihydropyridine. The substituents could be easily modi- [a] 466 fied by altering the substrates to obtain tri-and tetraarylpyridines including bipyridines and terpyridine. Synthesis of differently substituted pentaarylpyridines was consequently achieved via only three steps from commercially available reagents with simple experimental manipulations.[a] 2 equiv. of enamine 1B were used.

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Tailor-made synthesis of fully alkylated/arylated nicotinates by FeCl₃-mediated condensation of enamino esters with enones

Cited by 40 publications

References 39 publications

α,β‐Unsaturated Aldehydes as C‐Building Blocks in the Synthesis of Pyridines, 1,4‐Dihydropyridines and 1,2‐Dihydropyridines

α,β‐Unsaturated Aldehydes as C‐Building Blocks in the Synthesis of Pyridines, 1,4‐Dihydropyridines and 1,2‐Dihydropyridines

Copper Catalysis for Nicotinate Synthesis through β‐Alkenylation/Cyclization of Saturated Ketones with β‐Enamino Esters

Three Step Synthesis of Fully and Differently Arylated Pyridines

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Tailor-made synthesis of fully alkylated/arylated nicotinates by FeCl3-mediated condensation of enamino esters with enones

Cited by 40 publications

References 39 publications

α,β‐Unsaturated Aldehydes as C‐Building Blocks in the Synthesis of Pyridines, 1,4‐Dihydropyridines and 1,2‐Dihydropyridines

α,β‐Unsaturated Aldehydes as C‐Building Blocks in the Synthesis of Pyridines, 1,4‐Dihydropyridines and 1,2‐Dihydropyridines

Copper Catalysis for Nicotinate Synthesis through β‐Alkenylation/Cyclization of Saturated Ketones with β‐Enamino Esters

Three Step Synthesis of Fully and Differently Arylated Pyridines

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Tailor-made synthesis of fully alkylated/arylated nicotinates by FeCl₃-mediated condensation of enamino esters with enones