Cyclofunctionalization and free-radical-based hydrogen-transfer reactions. An iterative reaction sequence applied to the synthesis of the C(7)-C(16) subunit of zincophorin.

Abstract

The strategy considered herein features an iodocyclofunctionalization/hydrogen-transfer reaction sequence for the elaboration of propionate motifs. Proceeding with excellent yield and diastereoselectivity, the synthetic sequence proposed gives access to the anti-anti dipropionate motif when the reduction step is performed under the control of the exocyclic effect. The tandem sequence is applied successfully to the synthesis of the C(7)-C(16) subunit of zincophorin, and iteration of the process gives the desired anti-anti-anti-anti polypropionate stereopentad. Modifications of the reaction sequence--including phenylselenocyclofunctionalization, carbonate hydrolysis, and chelation-controlled radical reduction reactions--lead to the formation of the anti-syn dipropionate motif with remarkable diastereocontrol.