Endo-oxacyclizations of polyepoxides: Biomimetic synthesis of fused polycyclic ethers

Frank E. McDonald, Fernando Bravo, Xia Wang, Xudong Wei, Motoki Toganoh, J. Ramón Rodríguez, Bao Do, Wade A. Neiwert, Kenneth I. Hardcastle

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

Boron trifluoride-etherate promotes the endo-selective oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The mechanism of the oxacyclization reaction probably involves intramolecular nucleophilic addition of epoxide oxygen to open another epoxide that is activated as an electrophile by the Lewis acid. These oxacyclizations proceed stereospecifically with inversion of configuration upon opening of each epoxide to provide trans-fused polycyclic products. The oxacyclization cascade is terminated by a tethered nucleophile, which may be the carbonyl oxygen of a ketone, ester, or carbonate, or a trisubstituted alkene. The best oxacyclization yields are generally observed with tert-butyl carbonate as the terminating nucleophile, although in some cases the oxacyclization products include formation of tert-butyl ethers as a minor product. The oxacyclization transformations described herein may mimic ring-forming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products.

Original languageEnglish
Pages (from-to)2515-2523
Number of pages9
JournalJournal of Organic Chemistry
Volume67
Issue number8
DOIs
Publication statusPublished - Apr 19 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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