Cycloaddition-rearrangement sequence of 2-amido substituted furans as a method of synthesizing hexahydroindolinones

Albert Padwa, Michael A. Brodney, Kyosuke Satake, Christopher S. Straub

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels-Alder cycloaddition (IMDAF) reaction of 2-amido substituted furans. The initially formed [4 + 2] cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The reaction rate and product yield were found to be markedly dependent upon the electronic properties of the alkenyl π-bond. 2-[2-(tert-Butoxycarbonylfuran-2-yl- amino)-ethyl]acrylic acid methyl ester was synthesized from 3- chlorocarbonyl-but-3-enoic acid methyl ester. Thermolysis of the carbomethoxy activated furanamide occurred at 80 °C to produce a rearranged hexahydroindolinone. When Me3Al or (MeO)3Al was used as a Lewis acid to promote the cycloaddition, a rearranged alcohol was obtained. The initially formed [4 + 2] cycloadduct undergoes ring opening in the presence of the Lewis acid, and the resulting aluminum intermediate delivers the substituent group from the same face as the neighboring oxygen to ultimately furnish a rearranged cis-alcohol. In contrast to this result, a mixture of diastereomeric methoxy alcohols was isolated when the IMDAF cycloaddition was carried out in methanol. The major isomer corresponds to the trans- diastereomer that results from trapping of the iminium ion from the less crowded face of the π-bond.

Original languageEnglish
Pages (from-to)4617-4626
Number of pages10
JournalJournal of Organic Chemistry
Volume64
Issue number13
DOIs
Publication statusPublished - Jun 25 1999
Externally publishedYes

Fingerprint

Furans
Cycloaddition
Lewis Acids
Alcohols
Esters
Oxygen
Deprotonation
Thermolysis
Ketones
Aluminum
Reaction products
Isomers
Electronic properties
Reaction rates
Methanol
Nitrogen
Ions
Acids
hexahydroindolinone

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Cycloaddition-rearrangement sequence of 2-amido substituted furans as a method of synthesizing hexahydroindolinones. / Padwa, Albert; Brodney, Michael A.; Satake, Kyosuke; Straub, Christopher S.

In: Journal of Organic Chemistry, Vol. 64, No. 13, 25.06.1999, p. 4617-4626.

Research output: Contribution to journalArticle

Padwa, Albert ; Brodney, Michael A. ; Satake, Kyosuke ; Straub, Christopher S. / Cycloaddition-rearrangement sequence of 2-amido substituted furans as a method of synthesizing hexahydroindolinones. In: Journal of Organic Chemistry. 1999 ; Vol. 64, No. 13. pp. 4617-4626.
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