An approach toward isoindolobenzazepines using the ammonium ylide/Stevens [1,2]-rearrangement sequence

A. Padwa, L. S. Beall, C. K. Eidell, K. J. Worsencroft

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Ammonium ylides derived from the Cu(II)-catalyzed decomposition of α-diazo carbonyls tethered to tertiary amines underwent a benzylic Stevens [1,2]-rearrangement to give tetrahydroisoquinolines or benzazepines containing fused five-membered rings, a feature found in the cephalotaxus alkaloids. Model studies were also carried out toward the synthesis of lennoxamine, a member of the isoindolobenzazepine family of alkaloids. The approach utilized is based on the Rh(II)-catalyzed reaction of an α-diazo carbonyl compound containing an amido group in the γ-position. Treatment of several N,N-dialkyl-substituted amido diazo-esters with Rh2(OAc)4 in benzene at 80 °C in the presence of several dienophiles gave [4 + 2]-cycloadducts derived from the Diels-Alder reaction of a transient α-amino isobenzofuran intermediate. In the absence of an external trapping agent, no rearranged product derived from an ammonium ylide intermediate could be detected in the crude reaction mixture. In contrast to this result, reaction of the related diazo dihydroisoquinoline amide 46 with Rh2(OAc)4 afforded the isoindolobenzazepine ring system in high yield. Formation of the 5,7-fused skeleton was rationalized in terms of a spirocyclic ammonium ylide that underwent a preferential Stevens [1,2]-shift of the benzylic carbon atom. While we were ultimately thwarted in using the ammonium ylide/rearrangement cascade for a lennoxamine synthesis by an uncooperative diazo transfer reaction, the cascade sequence was shown to be useful for the preparation of various isoindolobenzazepines.

Original languageEnglish (US)
Pages (from-to)2414-2421
Number of pages8
JournalJournal of Organic Chemistry
Volume66
Issue number7
DOIs
StatePublished - Apr 6 2001

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Ammonium Compounds
Harringtonines
Benzazepines
Tetrahydroisoquinolines
Carbonyl compounds
Benzene
Alkaloids
Amides
Amines
Esters
Carbon
Decomposition
Atoms
lennoxamine
dirhodium tetraacetate

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

An approach toward isoindolobenzazepines using the ammonium ylide/Stevens [1,2]-rearrangement sequence. / Padwa, A.; Beall, L. S.; Eidell, C. K.; Worsencroft, K. J.

In: Journal of Organic Chemistry, Vol. 66, No. 7, 06.04.2001, p. 2414-2421.

Research output: Contribution to journalArticle

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