A macrocycle directed total synthesis of di--methylendiandrin A

The total synthesis of the lignan-based cyclobutane di- O -methylendiandrin A has been achieved using diastereoselective, vicinal alkylation and transannular McMurry reactions of a macrocyclic 1,4-diketone as key transformations for establishing relative stereochemistry and furnishing the strained 4-membered ring of the natural product. The synthesis of di- O -methylendiandrin A has been achieved using diastereoselective, vicinal alkylation and transannular McMurry reactions of a macrocyclic 1,4-diketone, to establish stereochemistry and the strained ring of the natural product.