Concise Total Syntheses of Leuconoxine‐Type Alkaloids Enabled by Palladium/Norbornene‐Catalyzed Pyrrole Difunctionalization
Year: 2025
Type: article
Abstract: Concise 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.
Institution: University of Chicago
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
Award: G486742774
OpenAlex ID: W4409001620