Toward the synthesis of the carbacylic ansa antibiotic kendomycin.

The convergent synthesis of a benzofuran analog of the carbacyclic ansa compound kendomycin has been achieved by assembling three major fragments by means of epoxide opening and directed ortho lithiation. The crucial tetrahydropyran ring was formed by a highly stereoselective cationic cyclization. Analysis of all synthesized tetrahydropyran-arene compounds reveals a hindered sp(2)-sp(3) rotation, which results in rotational isomers or atropisomers affecting macrocyclization reactions. The latter could only be achieved by means of Horner-Wadsworth-Emmons olefination.