Welwistatin Support Studies: Expansion and Limitation of Aryllead(IV) Coupling Reactions

摘要

Recent support studies on the total synthesis of the welwitstatin system are described. The target step involves lead-mediated arylation of sterically demanding aryl groups and carbon acid coupling partners in order to establish the highly congested tetracyclic core structure. Type >7 β-ketoesters and β-ketonitriles were successfully arylated with a variety of ortho- and meta-subsituted aryllead compounds generated by a halogen-boron-lead exchange sequence. The enolates of compounds >15, >19 and >25, each bearing all-carbon quaternary centers adjacent to the arylation site, failed to couple.