Novel chemistry of alpha-tosyloxy ketones: applications to the solution- and solid-phase synthesis of privileged heterocycle and enediyne libraries

Research output: Contribution to journalJournal articleResearchpeer-review

  • K C Nicolaou
  • T Montagnon
  • Ulven, Trond
  • P S Baran
  • Y-L Zhong
  • F Sarabia
New synthetic technologies for the preparation and elaboration of alpha-tosyloxy ketones in solution- and on solid-phase are described. Both olefins and ketones serve as precursors to these relatively stable chemical entities: olefins via a novel one-pot epoxidation, arylsulfonic acid displacement, and oxidation sequence, and ketones by direct exposure to arylsulfonic acids in the presence of diacetoxy iodobenzene. Reaction of these substrates with O-, S-, or N-centered nucleophiles leads to incorporation of the nucleophile with concomitant expulsion of the sulfonate, while exposure to bis-functional nucleophiles furnishes annulated heterocyclic systems. In addition, the reactions of carbon-centered nucleophiles with alpha-tosylyloxy ketones are also explored. The collated data for all these nucleophiles provide compelling evidence for the proposal that different reaction pathways are followed when alpha-tosyloxy ketones are engaged by "hard" versus "soft" nucleophiles. The accessibility and site-selectivity of the chemistry demonstrated herein offer the promise of an expanded use for this moiety in solid-phase library construction, in particular, and in the field of organic synthesis, in general.
Original languageEnglish
JournalAmerican Chemical Society. Journal
Volume124
Issue number20
Pages (from-to)5718-5728
Number of pages11
ISSN0002-7863
Publication statusPublished - 22 May 2002

    Research areas

  • Alkynes, Heterocyclic Compounds, Ketones, Tosyl Compounds

ID: 189160785