Transannular <i>O</i> ‐Heterocyclization Reactions of Cyclododeca‐1,5,9‐triene Derivatives: A New Concept for the Preparation of Key Intermediates for Total Syntheses of Annonaceous Acetogenins

ABSTRACT Transannular π‐cyclizations and heterocyclizations are characteristic for electrophilic addition reactions to medium‐sized cycloalka‐1,5‐dienes. Transannular O ‐heterocyclizations have been frequently observed in reactions of cycloocta‐1,5‐diene and derivatives, but rarely for larger rings. Now this reaction type has been extended for diastereoisomeric cyclododeca‐1,5,9‐trienes to form 2,9‐disubstituted 13‐oxabicyclo[8.2.1]tridec‐5‐enes, creating four stereogenic centers in racemic form in one step. Ozonolytic cleavage of the remained double bond provided cis ‐1,5‐dialkylated tetrahydrofuran derivatives bearing functional groups like halogen or hydroxyl in β‐ and β′‐positions regarding the tetrahydrofuran‐oxygen and carboxyl functions at the ends of both alkyl groups. Applying differently substituted cyclododeca‐1,5‐diene derivatives such as epoxides or vicinal diols as starting materials, diastereoisomers of the above‐mentioned tetrahydrofurans have been prepared in four or five steps. These compounds have the potential to serve as Lego‐like building blocks for syntheses of annonaceous acetogenins.