Opening of aryl-substituted epoxides to form quaternary stereogenic centers: synthesis of (-)-mesembrine.
[reaction: see text] Cycloalkanones are easily converted into aryl-substituted cyclic alkenes by the addition of an aryl Grignard reagent followed by dehydration. These alkenes are good substrates for asymmetric epoxidation. We have found that the addition of allylic and benzylic Grignard reagents can occur preferentially at the benzylic position of the derived epoxides to give the quaternary stereogenic center. This approach led to a short synthesis of the nanomolar serotonin re-uptake inhibitor (-)-mesembrine.
Taber
Douglass F
DF
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA. Taberdf@udel.edu
He
Yigang
Y
D026121:Indole Alkaloids / Q000138:chemical synthesis*; D013237:Stereoisomerism
D026121:Indole Alkaloids; C011300:mesembrine