Tandem [4+1+1] Annulation Approach to 4-Acyl-3,4-dihydropyrrolo[1,2- a]pyrazines: Diastereoselective Construction of Dihydropyrazine Units from Pyrroles

Anuradha Dagar, Gi Hun Bae, Jeong Hwa Lee, Ikyon Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Efficient construction of new chemical space by way of strategic use of tandem reactions is highly important in drug discovery. Described herein is an atom-economical [4+1+1] annulation approach to 3-(hetero)aryl-4-acyl-3,4-dihydropyrrolo[1,2-a]pyrazines, a new chemical space, via a one-pot three-component reaction under mild reaction conditions. Formation of multiple bonds (one C-C and two C-N) was achieved by a cascade reaction sequence consisting of generation of a Schiff base, a diastereoselective Mannich reaction, and intramolecular imine formation. This modular and environment-friendly process allowed rapid access to a wide range of 4-acylated 3,4-dihydropyrrolo[1,2-a]pyrazines and their analogues, opening opportunity to explore biological activity associated with this scaffold.

Original languageEnglish
Pages (from-to)6916-6927
Number of pages12
JournalJournal of Organic Chemistry
Volume84
Issue number11
DOIs
Publication statusPublished - 2019 Jun 7

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Pyrazines
Pyrroles
Imines
Schiff Bases
Scaffolds (biology)
Bioactivity
Atoms
Drug Discovery

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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title = "Tandem [4+1+1] Annulation Approach to 4-Acyl-3,4-dihydropyrrolo[1,2- a]pyrazines: Diastereoselective Construction of Dihydropyrazine Units from Pyrroles",
abstract = "Efficient construction of new chemical space by way of strategic use of tandem reactions is highly important in drug discovery. Described herein is an atom-economical [4+1+1] annulation approach to 3-(hetero)aryl-4-acyl-3,4-dihydropyrrolo[1,2-a]pyrazines, a new chemical space, via a one-pot three-component reaction under mild reaction conditions. Formation of multiple bonds (one C-C and two C-N) was achieved by a cascade reaction sequence consisting of generation of a Schiff base, a diastereoselective Mannich reaction, and intramolecular imine formation. This modular and environment-friendly process allowed rapid access to a wide range of 4-acylated 3,4-dihydropyrrolo[1,2-a]pyrazines and their analogues, opening opportunity to explore biological activity associated with this scaffold.",
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Tandem [4+1+1] Annulation Approach to 4-Acyl-3,4-dihydropyrrolo[1,2- a]pyrazines : Diastereoselective Construction of Dihydropyrazine Units from Pyrroles. / Dagar, Anuradha; Bae, Gi Hun; Lee, Jeong Hwa; Kim, Ikyon.

In: Journal of Organic Chemistry, Vol. 84, No. 11, 07.06.2019, p. 6916-6927.

Research output: Contribution to journalArticle

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