Synthesis of (±)-isoretronecanol, (±)-curassanecine, (±)-heliotridane, (±)-tashiromine and (±)-5-epitashiromine via α-(N-carbamoyl)alkylcuprate chemistry

Vinylation of N-Boc-2-pyrrolidinylcuprate reagents with functionalized vinyl iodides followed by N-Boc deprotection and cyclization affords 1-methylidine pyrrolizidine and indolizidine carbon skeletons. Functional group manipulation of the exo-cyclic olefin provides direct synthetic entries to the pyrrolizidine alkaloids (±)-isoretronecanol, (±)-curassanecine, (±)-heliotridane or the indolizidine alkaloids (±)-tashiromine and (±)-epitashiromine. This synthetic approach to pyrrolizidine and indolizidine alkaloids requires masking of the tertiary amine during functional group interconversions involving the alkene functionality.