Total Synthesis of (−)‐Vindorosine

Outlined herein is a novel and scalable synthesis of (−)‐vindorosine based on two key transformations. A highly diastereoselective vinylogous Mannich addition of dioxinone‐derived lithium dienolates with indolyl N‐tert‐butanesulfinyl imines has been developed. In addition, an intramolecular Heathcock/aza‐Prins cyclization was introduced to construct both the C, and the highly substituted E rings for the synthesis of (−)‐vindorosine and related alkaloids. In total: A new strategy for the synthesis of (−)‐vindorosine and related alkaloids features an asymmetric vinylogous Mannich addition of dioxinone‐derived lithium dienolates to indolyl N‐tert‐butanesulfinyl imines, and an intramolecular Heathcock/aza‐Prins cyclization to construct the C and E rings. Tf=trifluoromethanesulfonyl, THF=tetrahydrofuran.