Enantioselective Synthesis of the Platensimycin Core by Silver(I)-Promoted Cyclization of Δ6 -α-Iodoketone

Abstract

A chiral-pool-based synthesis of the platensimycin core was achieved using (S)-lactic acid as an inexpensive starting material. The cyclohexenone ring was closed in a Mukaiyama-Michael domino sequence, while the quaternary stereocenter was created by a highly stereoselective decarboxylative allylation. The spirobicyclic skeleton was constructed by a RCM reaction. A new silver(I)-promoted cyclization reaction of Δ⁶ - and Δ⁷ -α-iodoketones was developed and applied for the pivotal carbon-carbon bond formation. The scope and limitations of this methodology are also presented.

Keywords: antibiotics; cyclization; natural products; silver; total synthesis.