Molecular Reconstruction with Stereochemical Relay: An Investigation into the Rearrangement of Spiro[4.5]decadienone
Satapanawat Sittihan1, Shingo Harada2, Tomohiro Isono2
1Program on Chemical Sciences, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, 906 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok, 10210, Thailand.
Abstract:
Herein, we report the unusual skeletal rearrangement of spiro[4.5]decadienone to benzoxepane. In particular, Lewis acid-promoted epoxide-opening ipso-cyclization of aryl epoxides afforded spiro[4.5]decadienone intermediates. Subsequent thermal activation assembled a benzoxepane core via rearomative molecular reorganization. The sequence was high-yielding and highly diastereoselective but sensitive to the aromatic substitution pattern and the epoxide side chain. Mechanistic studies suggested that the rearrangement proceeded via an uncommon intramolecular enolate attack onto the electrophilic O of p-quinone oxonium zwitterion. DFT calculations helped rationalize the product distribution and the origin of diastereoselectivity. Initial investigation into the application of this chemical transformation is also presented.
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