Application of 1,3‐Dipolar Reactions between Azomethine Ylides and Alkenes to the Synthesis of Catalysts and Biologically Active Compounds

Arrastia, Iosune; Arrieta, Ana; Cossío, Fernando P.

doi:10.1002/ejoc.201800911

Cited by 69 publications

(24 citation statements)

References 103 publications

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“…The second approach to the 2‐(hetero)arylpyrrolidines is based on the formation of pyrrolidine ring from acyclic precursors. Within this approach, intermolecular cycloaddition reactions play a significant role, [3+2] dipolar cycloadditions being the most used ones . The methods based on the intramolecular cyclization of acyclic precursors are also widely used, especially in the case of polycyclic systems .…”

Section: Introductionmentioning

confidence: 99%

Acid‐Catalyzed Cascade Reaction of 4‐Aminobutanal Derivatives with (Hetero)aromatic Nucleophiles: A Versatile One‐Pot Access to 2‐(Hetero)arylpyrrolidines.

et al. 2019

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2‐(Hetero)arylpyrrolidine fragment is found in a diverse array of biologically active molecules, both natural and unnatural. In recent years, a substantial increase in number of approved drugs featuring this scaffold is observed. Developing methods for the synthesis of such compounds has been essential for making progress in this field. Most of these methods require usage of metal catalysts and introduce additional chemical steps to obtain appropriately substituted starting compounds. This microreview details the one‐pot approach for the synthesis of pyrrolidine derivatives possessing (hetero)aromatic substituent at the second position of pyrrolidine ring based on usage of readily available N‐substituted 4,4‐diethoxybutan‐1‐amines and (hetero)aromatics as starting compounds and Bronsted acids as catalysts.

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Section: Introductionmentioning

confidence: 99%

Acid‐Catalyzed Cascade Reaction of 4‐Aminobutanal Derivatives with (Hetero)aromatic Nucleophiles: A Versatile One‐Pot Access to 2‐(Hetero)arylpyrrolidines.

et al. 2019

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“…The full reaction pathway was investigated with the substrates 33 , 1a (R 1 = Ph, R 2 = H) and a simplified ligand ( R )- 2a (methyl groups were used instead of phenyl groups on the phosphorus). The DFT calculations indicated that the Ag(I)/( R )- L2a -catalyzed 1,3-DC of β-sulfonyl acrylates proceeded via a stepwise Michael addition/Mannich pathway . The calculations also revealed that the two H-bonding interactions between the two electron-withdrawing groups of the ( Z )-sulfonyl acrylate and the NH 2 group of the chiral ligand accounted for the high endo -selectivity (Scheme b).…”

Section: Catalytic Asymmetric 13-dipolar Cycloaddition Of N-metallate...mentioning

confidence: 97%

Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides

2020

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Conspectus Optically active nitrogen-containing compounds have attracted substantial attention due to their ubiquity in the cores of natural products and bioactive molecules. Among the various synthetic approaches to nitrogenous frameworks, catalytic asymmetric 1,3-dipolar cycloadditions are one of the most attractive methods because of their powerful ability to rapidly construct various chiral N-heterocycles. In particular, N-metallated azomethine ylides, common and readily available 1,3-dipoles, have been extensively applied in dipolar cycloaddition reactions. Despite the fact that asymmetric transformations of azomethine ylides have been investigated for decades, most of the efforts have been directed toward the preparation of pyrrolidines using glycinate-derived α-unsubstituted aldimine esters as the precursors of the azomethine ylides. While α-substituted azomethine ylides derived from amino esters other than glycinate have seldom been harnessed, the construction of non-five-membered chiral N-heterocycles via 1,3-dipolar cycloadditions remains underexplored. In addition, the asymmetric α-functionalization of aldimine esters to prepare acyclic nitrogenous compounds such as α-amino acids, in which an in situ-generated N-metallated azomethine ylide serves as the nucleophile, has not been sufficiently described. In this Account, we mainly discuss the achievements we have made in the past decade toward broadening the applications of N-metallated azomethine ylides for the preparation of nitrogen-containing compounds. We began our investigation with the design and synthesis of a new type of chiral ligand, TF-BiphamPhos, which not only coordinates with Lewis acids to activate dipolar species but also serves as an H-bond donor to increase the reactivity of dipolarophiles with significantly enhanced stereochemical control. Using the Cu(I) or Ag(I)/TF-BiphamPhos complex as the catalyst, we achieved highly stereoselective (3+2) cycloadditions of glycinate and non-glycinate-derived azomethine ylides with diverse dipolarophiles, producing a variety of enantioenriched pyrrolidines with multiple stereocenters in a single step. To further expand the synthetic utility of N-metallated azomethine ylides, we successfully developed higher order cycloadditions with fulvenes, tropone, 2-acyl cycloheptatrienes, and pyrazolidinium ylides serving as the reaction partner, and this reaction provides straightforward access to enantioenriched fused piperidines, bridged azabicyclic frameworks, and triazines via (3+6)- and (3+3)-type cycloadditions. Using N-metallated azomethine ylides as the nucleophile, we realized Cu(I)-catalyzed asymmetric 1,4-Michael additions with α,β-unsaturated bisphosphates/Morita–Baylis–Hillman products, furnishing an array of structurally diverse unnatural α-amino acids. Based on the strategy of synergistic activation, we achieved highly efficient dual Cu/Pd and Cu/Ir catalysis for the α-functionalization of aldimine esters via the asymmetric allylic/allenylic alkylation of N-metallated azomethine ylides. No...

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“…[ 3–6 ] In simple, the pyrrole derivative of interest can be synthesized just by tuning azomethineylide and dipolarophile. [ 7–9 ] In addition to this, they may react with carbonyl compounds to yield oxazolidine derivatives. [ 10,11 ] Hence many reports are available in the literature for such cycloadditions, especially by using electron‐deficient alkenes and alkynes as dipolarophiles such as α,β‐unsaturated carbonyl compounds and nitro compounds.…”

Section: Introductionmentioning

confidence: 99%

One‐pot three‐component 1,3‐dipolar cycloaddition of azomethineylides to nitrofuran containing acetylenic ketones and molecular docking studies of the cycloadducts

Kadambar

Kalluraya

Kumar

2020

Journal of Heterocyclic Chem

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One‐pot three‐component 1,3‐dipolar cycloaddition reaction of azomethineylides generated from various combinations of isatin and ninhydrin with α‐aminoacids to 5‐nitrofurancontaining acetylenic ketones was carried out under thermal and microwave methods. The study of the regiochemical trend during the cycloaddition suggested that the nitrofuran ring exert no effect on the regiochemistry of the reaction as observed in the case of nitrofuran containing chalcones. The reason for the nil influence of the nitrofuran group is attributed to the increased electron density due to the triple bond. The newly synthesized compounds were docked to the active site of human anaplastic lymphoma kinase (ALK) to know the cancer cell toxicity in silico. The compounds 4b and 5a showed good binding interactions with the target in the active site.

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Application of 1,3‐Dipolar Reactions between Azomethine Ylides and Alkenes to the Synthesis of Catalysts and Biologically Active Compounds

Cited by 69 publications

References 103 publications

Acid‐Catalyzed Cascade Reaction of 4‐Aminobutanal Derivatives with (Hetero)aromatic Nucleophiles: A Versatile One‐Pot Access to 2‐(Hetero)arylpyrrolidines.

Acid‐Catalyzed Cascade Reaction of 4‐Aminobutanal Derivatives with (Hetero)aromatic Nucleophiles: A Versatile One‐Pot Access to 2‐(Hetero)arylpyrrolidines.

Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides

One‐pot three‐component 1,3‐dipolar cycloaddition of azomethineylides to nitrofuran containing acetylenic ketones and molecular docking studies of the cycloadducts

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