Total synthesis of (-)-(alpha)-kainic acid via a diastereoselective methylenecyclopropane ring expansion.
[reaction: see text] A concise and enantioselective synthesis of (-)-(alpha)-kainic acid in 13 steps with an overall yield of 15% is reported. The pyrrolidine kainoid precursor with the required C2/C3 trans stereochemistry was prepared with excellent diastereoselectivity (>20:1) via a MgI(2)-mediated ring expansion of a tertiary methylenecyclopropyl amide. A selective hydroboration was then employed to set the remaining stereochemistry at the C4 position en route to (-)-(alpha)-kainic acid.
Scott
Mark E
ME
Davenport Research Laboratories, Department of Chemistry, University of Toronto, Ontario, Canada.
Lautens
Mark
M
D003500:Cyclization; D003521:Cyclopropanes / Q000737:chemistry*; D007202:Indicators and Reagents; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D003521:Cyclopropanes; D007202:Indicators and Reagents; C508672:methylenecyclopropane; D007608:Kainic Acid