Evolution of an oxidative dearomatization enabled total synthesis of vinigrol

Qingliang Yang, Cristian Draghici, Jon T Njardarson, Fang Li, Brandon R. Smith, Pradipta Das

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The evolution of the synthetic strategy resulting in a total synthesis of vinigrol is presented. Oxidative dearomatization/intramolecular Diels-Alder cycloaddition has served as the successful cornerstone for all of the approaches. Extensive radical cyclization efforts to form the tetracyclic core resulted in interesting and surprising reaction outcomes, none of which could be advanced to vinigrol. These cyclization obstacles were successfully overcome by using Heck instead of radical cyclizations. The total synthesis features a trifluoroethyl ether protecting group being used for the first time in organic synthesis. The logic of its selection and the group's importance beyond protecting the C8a hydroxyl group is presented along with a discussion of strategies for its removal. Because of the compact tetracyclic cage the route is built around many unusual reaction observations and solutions have emerged. For example, a first of its kind Grob fragmentation reaction featuring a trifluoroethyl leaving group has been uncovered, interesting interrupted selenium dioxide allylic oxidations have been observed as well as intriguing catalyst and counterion dependent directed hydrogenations.

Original languageEnglish (US)
Pages (from-to)330-344
Number of pages15
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number2
DOIs
StatePublished - Jan 14 2014

Fingerprint

Cyclization
Selenium Oxides
synthesis
Synthetic Chemistry Techniques
Hydrogenation
Cycloaddition
Cycloaddition Reaction
Hydroxyl Radical
Ether
cycloaddition
selenium
dioxides
hydrogenation
logic
ethers
Oxidation
fragmentation
Catalysts
routes
catalysts

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Evolution of an oxidative dearomatization enabled total synthesis of vinigrol. / Yang, Qingliang; Draghici, Cristian; Njardarson, Jon T; Li, Fang; Smith, Brandon R.; Das, Pradipta.

In: Organic and Biomolecular Chemistry, Vol. 12, No. 2, 14.01.2014, p. 330-344.

Research output: Contribution to journalArticle

Yang, Qingliang ; Draghici, Cristian ; Njardarson, Jon T ; Li, Fang ; Smith, Brandon R. ; Das, Pradipta. / Evolution of an oxidative dearomatization enabled total synthesis of vinigrol. In: Organic and Biomolecular Chemistry. 2014 ; Vol. 12, No. 2. pp. 330-344.
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