Stereodivergent Synthesis of the C1-C9 Tetrahydropyran Subunit of Zincophorin and Isomers Thereof

Zincophorin C1-C9 fragment and seven tetrahydropyran analogues were prepared diastereoselectively by sequential iodoetherification and radical hydrogen-transfer reactions. Stereoselective formation of 3,7-trans or 3,7-cis rings was rationalized through minimization of allylic-1,3 strain in chair-like transition states. Subsequent hydrogen-transfer provided 7,8-anti or 7,8-syn isomers under acyclic stereocontrol or endocyclic control respectively. The latter approach relies on the formation of a [4.4.0] bicyclic complexes resulting from the chelation of the oxygen of the tetrahydropyran ring and the ester by a bidentate Lewis acid.