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.