Total synthesis of (±)-3-demethoxyerythratidinone via Tf2O-promoted cascade reaction of enaminone.

ABSTRACT

The tetracyclic rings with chiral quaternary center represent a formidable synthetic challenge for Erythrina alkaloids. We present a 6-step synthesis of the Erythrina alkaloid 3-demethoxyerythratidinone with a 16% overall yield. Our synthesis highlights a cascade reaction initiated by Tf2O-induced activation of an enaminone substrate, yielding an iminium species and an enol triflate, followed by a Pictet-Spengler reaction. This method efficiently constructs the tetracyclic core skeleton, featuring an N-substituted quaternary center. It exhibits versatility across diverse (hetero)arenes and enaminone structures, providing a general strategy for the rapid synthesis of fused or spiro ring systems including the core structure of homoerythrina alkaloids.