6-Bromomethyl-4H-1,3-dioxin

A versatile bromomethyl vinyl ketone equivalent for heterocycle and carbocycle construction

Thomas J. Greshock, Raymond Lee Funk

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

6-Bromomethyl-4H-1,3-dioxin has been prepared in three steps from allyl iodide. A variety of enolates were then alkylated with this bromide. The resulting 6-alkyl-4H-1,3-dioxins were either subjected to further multistep transformations and/or heated to effect facile retrocycloaddition reactions. The resulting enones smoothly participated in novel endo-conjugate addition reactions with both carbon and nitrogen nucleophiles. For example, several bicyclo[4.3.1]decan-3,10-diones, the carbon framework of the CP compounds, were constructed using this novel annulation strategy. In another natural product study, a benzazocine related to the heterocyclic framework of the ring-opened tautomeric form of FR-900482 was also prepared using this methodology. Finally, a piperidin-4-one obtained from a 6-endo conjugate addition was converted to the naturally occurring (2S,4R)-4-hydroxypipecolic acid. Collectively, these examples document the synthetic equivalency of dioxin 1 with bromomethyl vinyl ketone and, moreover, delineate a strategy for accomplishing the sequential reactions with nucleophiles at the α- followed by the β electrophilic sites.

Original languageEnglish (US)
Pages (from-to)754-755
Number of pages2
JournalJournal of the American Chemical Society
Volume124
Issue number5
DOIs
StatePublished - Feb 6 2002

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Nucleophiles
Dioxins
Ketones
Carbon
Addition reactions
Iodides
Biological Products
Bromides
Nitrogen
Acids
6-bromomethyl-4H-1,3-dioxin
4-hydroxypipecolic acid
5-(4-trimethylammoniumphenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin
FR 900482

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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abstract = "6-Bromomethyl-4H-1,3-dioxin has been prepared in three steps from allyl iodide. A variety of enolates were then alkylated with this bromide. The resulting 6-alkyl-4H-1,3-dioxins were either subjected to further multistep transformations and/or heated to effect facile retrocycloaddition reactions. The resulting enones smoothly participated in novel endo-conjugate addition reactions with both carbon and nitrogen nucleophiles. For example, several bicyclo[4.3.1]decan-3,10-diones, the carbon framework of the CP compounds, were constructed using this novel annulation strategy. In another natural product study, a benzazocine related to the heterocyclic framework of the ring-opened tautomeric form of FR-900482 was also prepared using this methodology. Finally, a piperidin-4-one obtained from a 6-endo conjugate addition was converted to the naturally occurring (2S,4R)-4-hydroxypipecolic acid. Collectively, these examples document the synthetic equivalency of dioxin 1 with bromomethyl vinyl ketone and, moreover, delineate a strategy for accomplishing the sequential reactions with nucleophiles at the α- followed by the β electrophilic sites.",
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6-Bromomethyl-4H-1,3-dioxin : A versatile bromomethyl vinyl ketone equivalent for heterocycle and carbocycle construction. / Greshock, Thomas J.; Funk, Raymond Lee.

In: Journal of the American Chemical Society, Vol. 124, No. 5, 06.02.2002, p. 754-755.

Research output: Contribution to journalArticle

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