Synthesis of Plakortolides E and I Enabled by Base Metal Catalysis

Abstract

A protecting-group-free synthesis of two endoperoxide natural products, plakortolide E and plakortolide I, is reported. Key-steps feature the use of earth-abundant transition metals, consisting of a vanadium-mediated epoxidation, an iron-catalyzed allylic substitution, and a cobalt-induced endoperoxide formation. Our approach combines redox-economy, chemoselective bond-forming reactions, and telescoping into one-pot operations to forge an overall efficient synthesis.

Synthesis of Plakortolides E and I Enabled by Base Metal Catalysis

“…By using Fe(OAc) 2 as catalyst, a chemoselective installation of the alkyl side chain was achieved in good yield. 29 This work demonstrates that a straightforward and protecting-group-free synthesis of endoperoxide natural products can be fueled by chemoselective transformations with earth-abundant transition-metal catalysts.…”

“…In conclusion, we have developed a concise synthesis of enantiopure (+)-plakortolide E ( 1 ) and (−)-plakortolide I ( 2 ) from commercially available ( R )-linalool ( 5 ). By using Fe­(OAc) 2 as catalyst, a chemoselective installation of the alkyl side chain was achieved in good yield . This work demonstrates that a straightforward and protecting-group-free synthesis of endoperoxide natural products can be fueled by chemoselective transformations with earth-abundant transition-metal catalysts.…”