Cyclization-cycloaddition cascades for the construction of azapolycyclic ring systems

Albert Padwa, William S. Kissell, Cheryl K Eidell

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cyclic 2-amidofuranones were obtained from the Rh(II)-catalyzed reaction of α-diazoketo substituted pyrrolidine derivatives. These compounds are derived by a [1,4]-hydrogen transfer from an initially formed carbonyl ylide dipole. Acylation of the amido-substituted furanone with pivalyl chloride provided a fused amidofuran, which underwent bimolecular Diels-Alder cycloaddition with N-phenylmaleimide. The Rh(II)-catalyzed decomposition of ethyl 2-diazo-3-oxo-(2-oxo-1-pent-4-enoyl-pyrrolidine-3-yl)propionate was also examined. In this case, the alkenyl group tethered to the amido carbonyl underwent smooth intramolecular [4+2]-cycloaddition with the amidofuran obtained from the acylation reaction. An alternate route for the synthesis of cyclic amidofurans was developed using a Pummerer induced cyclization of the thiophenyl substituted acetal derived from the aldol reaction of methoxyphenylsulfanyl acetaldehyde with α-valerolactam. Treatment of the amido-substituted acetal with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) generated an oxonium ion, which readily cyclized onto the adjacent carbonyl group. The amidofuran that was formed underwent an intramolecular Diels-Alder reaction when heated at 110°C in toluene. Subsequent ring opening of the transient [4+2]-cycloadduct followed by elimination of methanol and tautomerization of the resulting cyclohexadienone gave rise to the observed phenolic lactam in good overall yield.

Original languageEnglish (US)
Pages (from-to)1681-1693
Number of pages13
JournalCanadian Journal of Chemistry
Volume79
Issue number11
DOIs
StatePublished - Dec 1 2001

Fingerprint

Acylation
Acetals
Cycloaddition
Cyclization
Lactams
Acetaldehyde
Propionates
Toluene
Methanol
Chlorides
Hydrogen
Ions
Derivatives
Decomposition
pyrrolidine
valerolactam
hydronium ion
N-phenylmaleimide
3-hydroxybutanal
dimethyl(methylthio)sulfonium

Keywords

  • Cyclization
  • Diazo-ketoamide
  • Diels-Alder
  • Intramolecular
  • Rhodium(II)

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Organic Chemistry

Cite this

Cyclization-cycloaddition cascades for the construction of azapolycyclic ring systems. / Padwa, Albert; Kissell, William S.; Eidell, Cheryl K.

In: Canadian Journal of Chemistry, Vol. 79, No. 11, 01.12.2001, p. 1681-1693.

Research output: Contribution to journalArticle

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AB - Cyclic 2-amidofuranones were obtained from the Rh(II)-catalyzed reaction of α-diazoketo substituted pyrrolidine derivatives. These compounds are derived by a [1,4]-hydrogen transfer from an initially formed carbonyl ylide dipole. Acylation of the amido-substituted furanone with pivalyl chloride provided a fused amidofuran, which underwent bimolecular Diels-Alder cycloaddition with N-phenylmaleimide. The Rh(II)-catalyzed decomposition of ethyl 2-diazo-3-oxo-(2-oxo-1-pent-4-enoyl-pyrrolidine-3-yl)propionate was also examined. In this case, the alkenyl group tethered to the amido carbonyl underwent smooth intramolecular [4+2]-cycloaddition with the amidofuran obtained from the acylation reaction. An alternate route for the synthesis of cyclic amidofurans was developed using a Pummerer induced cyclization of the thiophenyl substituted acetal derived from the aldol reaction of methoxyphenylsulfanyl acetaldehyde with α-valerolactam. Treatment of the amido-substituted acetal with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) generated an oxonium ion, which readily cyclized onto the adjacent carbonyl group. The amidofuran that was formed underwent an intramolecular Diels-Alder reaction when heated at 110°C in toluene. Subsequent ring opening of the transient [4+2]-cycloadduct followed by elimination of methanol and tautomerization of the resulting cyclohexadienone gave rise to the observed phenolic lactam in good overall yield.

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