Synthesis of medium ring ethers by oxonium ylide formation and β-silyl directed ring expansion

WCC 16

Judy M. Suh, and Jim Li. Department of Medicinal Chemistry, Roche Palo Alto, 3414 Hillview Avenue, Palo Alto, CA 94304
Medium ring ethers are ubiquitous in nature, as they are found in red algal metabolites such as laurencia and laurenyne, and, as a subcomponent, in toxins such as brevetoxins and ciguatoxins. Despite the extensive efforts aimed at the development of general methods for the construction of medium ring ethers, there still remains a need for more efficient methods. Here we present a novel synthesis of medium ring ethers from β-silyl tetrahydrofurans: under lewis acid catalysis, a β-silyl tetrahydrofuran with a carbene tether undergoes an intramolecular carbene insertion to form a bicyclic oxonium ylide, which in turn expands into an oxocene following a β-silyl fragmentation. This methodology was utilized in the synthesis of α,β-disubstituted oxocene and α,α',β-trisubstituted oxocene, a key structural component of laurencine. The multi-step synthetic route to the penultimate tetrahydrofurans, the execution of the reaction, the stereochemical elucidation of the oxocenes by NMR studies, and lastly, our efforts toward the formal total synthesis of (+)-laurencine will be discussed.


The Merck Index Women in Chemistry
2:30 PM-4:30 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- Hall D, Poster

Women Chemists Committee

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009