Transition-Metal-Free, Atom- and Step-Economic Synthesis of Aminoketopyrrolizines from Benzylamine, Acylethynylpyrroles, and Acylacetylenes

Собенина, Л. Н.; Tomilin, Denis N.; Sagitova, Elena F.; Ushakov, Igor А.; Трофимов, Б. А.

doi:10.1021/acs.orglett.7b00408

Cited by 14 publications

(4 citation statements)

References 71 publications

(32 reference statements)

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“…It incorporates the accompanying key advances: (I) the base‐catalyzed (K 3 PO 4 /DMSO) expansion of benzylamine to 2‐acylethynylpyrroles and (ii) corresponding catalyst‐free expansion of enaminones subsequently acquired to acylacetylenes succeeded by intramolecular cyclization of the intermediates pentadiendiones, accordingly shaped to give the objective 1‐(benzylamino)‐2‐acyl‐3‐methylenoacylpyrrolizines (Scheme 146). [164] …”

Section: C−h Functionalization Of Pyrrolesmentioning

confidence: 99%

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Hunjan

Panday

Gupta

et al. 2021

The Chemical Record

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Among the known aromatic nitrogen heterocycles, pyrrole represents a privileged aromatic heterocycle ranging its occurrence in the key component of “pigments of life” to biologically active natural products to active pharmaceuticals. Pyrrole being an electron‐rich heteroaromatic compound, its predominant functionalization is legendary to aromatic electrophilic substitution reactions. Although a few excellent reviews on the functionalization of pyrroles including the reports by Baltazzi in 1963, Casiraghi and Rassu in 1995, and Banwell in 2006 are available, they are fragmentary and over fifteen years old, and do not cover the modern aspects of catalysis. A review covering a comprehensive package of direct functionalization on pyrroles via catalytic and non‐catalytic methods including their translational potential is described. Subsequent to statutory yet concise introduction, the classical functionalization on pyrroles using Lewis acids largely following an ionic mechanism is discussed. The subsequent discussion follows the various metal‐catalyzed C−H functionalization on pyrroles, which are otherwise difficult to implement by Lewis acids. A major emphasize is given on the radical based pyrrole functionalization under metal‐free oxidative conditions, which is otherwise poorly highlighted in the literature. Towards the end, the current development of pyrrole functionalization under photocatalyzed and electrochemical conditions is appended. Only a selected examples of substrates and important mechanisms are discussed for different methods highlighting their scopes and limitations. The aromatic nucleophillic substitution on pyrroles (being an electron‐rich heterocycle) happened to be the subject of recent investigations, which has also been covered accentuating their underlying conceptual development. Despite great achievements over the past several years in these areas, many challenges and problems are yet to be solved, which are all discussed in summary and outlook.

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Section: C−h Functionalization Of Pyrrolesmentioning

confidence: 99%

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Hunjan

Panday

Gupta

et al. 2021

The Chemical Record

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“…On the platform of acylethynylpyrroles 52, a new general strategy for the synthesis of functionalized pyrrolizines was developed [80]. It consisted of the two steps: (i) the base-catalyzed addition of a benzylamine to 2-acylethynylpyrroles 52 to give pyrrolylaminoenones 62; (ii) non-catalyzed addition of N-benzyl(pyrrolyl)aminoenones 62 to the triple bond of acylacetylenes 63 followed by the intramolecular cyclization of the intermediate pentadiendiones 64 thus formed to 1-benzylamino-2-acyl-3-methylenoacylpyrrolizines 65 (Scheme 35).…”

Section: Synthesis Of Pyrrolizines Via Three-component Cyclization Wimentioning

confidence: 99%

Recent Strides in the Transition Metal-Free Cross-Coupling of Haloacetylenes with Electron-Rich Heterocycles in Solid Media

Собенина

Трофимов

2020

Molecules

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The publications covering new, transition metal-free cross-coupling reactions of pyrroles with electrophilic haloacetylenes in solid medium of metal oxides and salts to regioselectively afford 2-ethynylpyrroles are discussed. The reactions proceed at room temperature without catalyst and base under solvent-free conditions. These ethynylation reactions seem to be particularly important, since the common Sonogashira coupling does not allow ethynylpyrroles with strong electron-withdrawing substituents at the acetylenic fragments to be synthesized. The results on the behavior of furans, thiophenes, and pyrazoles under the conditions of these reactions are also provided. The reactivity and structural peculiarities of nucleophilic addition to the activated acetylene moiety of the novel C-ethynylpyrroles are considered.

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“…This amination represents a typical nucleophilic addition of ammonia to the triple bond and, hence, the adducts fit trans-addition mode, common for such processes. 16 Consequently, formation of the intermediate trans-anion predetermines the location of the amino and acyl groups on the same side of the double bond, i.e. the Z-configuration.…”

Section: Paper Synthesismentioning

confidence: 99%

“…In comparison with the cyclization of dienes 4b,e,f to the corresponding pyridines (Scheme 7), heating at 130 °C for 6 h without solvent of diene 5 with a benzyl substituent, previously synthesized by the reaction of ethynylpyrrole 1e with benzylamine and benzoylacetylene, 16 produced a complex mixture of tar-like unidentified products. Nevertheless, the pyridine 3f without the benzyl group was isolated in 9% (Scheme 10).…”

Section: Paper Synthesismentioning

confidence: 99%

Highly Functionalized Pyrrolylpyridines from 2-(Acylethynyl)-pyrroles

Tomilin

Собенина²,

Ushakov³

et al. 2020

Synthesis

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A novel family of pharmaceutically prospective, densely functionalized (aryl-, hetaryl-, acyl-, and vinyl-substituted) pyrrolylpyridines has been assembled in up to 95% yields via the amination (NH4Cl/K2CO3/DMSO system, 90 °C, 16 h) of 2-(acylethynyl)pyrroles, followed by cyclization (MeOH, reflux, 6 h, up to 90% yield) of the formed intermediate 1-(pyrrol-2-yl)-1-aminoenones with acetylenic ketones (Bohlmann–Rahtz reaction). The intermediate pyrrolyl aminodienones, prospective building blocks for organic synthesis, can be separately synthesized (DMSO, 90 °C, 6 h) in 70–86% yields. A novel facet of this chemistry is stereoselective synthesis of C-vinylated pyridines, (E)-3-[5-acyl-2-aryl-6-(pyrrol-2-yl)pyridin-3-yl]-1-arylprop-2-en-1-ones, by involving the second molecule of acylacetylene into the reaction.

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Transition-Metal-Free, Atom- and Step-Economic Synthesis of Aminoketopyrrolizines from Benzylamine, Acylethynylpyrroles, and Acylacetylenes

Cited by 14 publications

References 71 publications

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Recent Strides in the Transition Metal-Free Cross-Coupling of Haloacetylenes with Electron-Rich Heterocycles in Solid Media

Highly Functionalized Pyrrolylpyridines from 2-(Acylethynyl)-pyrroles

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