Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide thiolysis, and intramolecular aldol reaction sequence. Reaction optimization studies identified room temperature as well as microwave-mediated procedures, providing moderate to good yields (57-88%) in the thiophenol-mediated epoxide opening and intramolecular aldol reaction. In addition, the isolation of a key intermediate and in situ NMR studies supported the mechanistic hypothesis. The bicyclic ring products occupy novel chemical space according to ChemGPS and Chemaxon chemical diversity and cheminformatics analyses.
|Number of pages||11|
|State||Published - Jul 31 2010|
Bibliographical noteFunding Information:
The authors thank Dr. Steven Geib (University of Pittsburgh) for the X-ray structure analyses of 14 and 20 , and NIH/NIGMS (P41GM081275; P50GM067082) for financial support.
- Chemical diversity analysis
- Epoxyketone rearrangement
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry