A cycloaddition approach toward the synthesis of substituted indolines and tetrahydroquinolines

A. Padwa, M. A. Brodney, B. Liu, Kyosuke Satake, T. Wu

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

The intramolecular Diels-Alder reaction of 2-substituted aminofurans (IMDAF) results in the formation of various indolines and tetrahydroquinolines. The isolation of these ring systems from the IMDAF reaction can be rationalized in terms of an initial [4 + 2]-cycloaddition that first produces an oxa-bridged cycloadduct, which was not detected since it readily underwent nitrogen-assisted ring opening. Proton exchange followed by an eventual dehydration provides the aromatic product. In certain cases, the intermediate cyclohexadienol can be isolated and independently converted to the final product in high yield. The starting 2-aminofurans were readily prepared from furanyl acyl azide by a Curtius rearrangement in the presence of an alcohol. Alkylation of the resulting N-alkyl carbamate with an alkenyl bromide allows for the synthesis of a wide variety of cycloaddition precursors. The scope of the IMDAF reaction was evaluated by using mono- and disubstituted alkenes, electron rich and electron deficient olefins, and acetylenic tethers. Cyclic 2-amidofurans were also synthesized using a related intramolecular Diels-Alder reaction of 2-amido-substituted oxazoles which contain a tethered alkyne. This transformation represents a new route to this rare heterocyclic ring system. The sequential cycloaddition method was used for a formal synthesis of the pyrrolophenanthridone alkaloid hippadine.

Original languageEnglish
Pages (from-to)3595-3607
Number of pages13
JournalJournal of Organic Chemistry
Volume64
Issue number10
DOIs
Publication statusPublished - 1999
Externally publishedYes

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Cycloaddition
Alkenes
Oxazoles
Alkynes
Carbamates
Azides
Electrons
Alkylation
Bromides
Dehydration
Alkaloids
Protons
Ion exchange
Nitrogen
Alcohols
1,2,3,4-tetrahydroquinoline
indoline

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

A cycloaddition approach toward the synthesis of substituted indolines and tetrahydroquinolines. / Padwa, A.; Brodney, M. A.; Liu, B.; Satake, Kyosuke; Wu, T.

In: Journal of Organic Chemistry, Vol. 64, No. 10, 1999, p. 3595-3607.

Research output: Contribution to journalArticle

Padwa, A. ; Brodney, M. A. ; Liu, B. ; Satake, Kyosuke ; Wu, T. / A cycloaddition approach toward the synthesis of substituted indolines and tetrahydroquinolines. In: Journal of Organic Chemistry. 1999 ; Vol. 64, No. 10. pp. 3595-3607.
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