Concise Total Syntheses of Leuconoxine‐Type Alkaloids Enabled by Palladium/Norbornene‐Catalyzed Pyrrole Difunctionalization

Abstract

AbstractConcise total syntheses of five leuconoxine‐type alkaloids, i.e., chloromelodinine, leuconodine A, leuconodine F, melodinine E, and leuconoxine, are achieved through a pyrrole‐centered strategy. The approach features a newly developed palladium/norbornene‐catalyzed pyrrole double C─H functionalization reaction to generate the core skeleton and a divergent oxidative dearomatization to complete the end game. In addition, no protecting group was employed, and the strategic use of a chloro substituent offers a number of advantages in these syntheses, which could have implications beyond this work. The discovery of an unusual chloro 1,2‐migration reaction enabled the first total synthesis of chloromelodinine E. This work represents the shortest syntheses of these natural products to date with 10–11 total steps.