Stereochemical study of a transannular Michael reaction cascade.

We systematically explored a transannular Michael reaction cascade for stereoselective synthesis of polycyclic systems. Both E,Z- and E,E-1,7-bis-enones in the form of 14-membered macrocyclic lactones underwent transannular cyclization to give polycyclic products with high efficiency and excellent diastereoselectivity. In contrast, Z,E- and Z,Z-macrocyclic lactones did not cyclize under similar reaction conditions. Our study revealed similarities and subtle stereochemical differences between this transannular cyclization process and transannular Diels-Alder reactions. An acyl ketene approach was developed for efficient synthesis of macrocyclic lactones. This investigation also illuminated the scope and limitation of macrocyclization by intramolecular Reformatsky reaction to prepare macrocyclic lactones.