Asymmetric total synthesis of rotenoids via organocatalyzed dynamic kinetic resolution

Abstract

Increasing effort has been made towards the asymmetric total synthesis of rotenoid natural products owing to their impressive biological and pharmaceutical activities. Here we report the modular asymmetric total synthesis of rotenoid natural products. The concise construction of the cis-fused tetrahydrochromeno[3,4-b]chromene core structure of rotenoids through N-heterocyclic carbene-catalyzed dynamic kinetic resolution is achieved, and a series of annulation products containing rotenoid key structures are rapidly assembled using this method. More importantly, the protocol enables the modular synthesis of a variety of rotenoid natural products in a highly convergent fashion, and the concise asymmetric total synthesis of tephrosin, the first asymmetric total synthesis of 12a-hydroxymunduserone, milletosin, and 12a-hydroxyrotenone, and the formal synthesis of deguelin are accomplished.