Stereochemical study of a transannular Michael reaction cascade

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Stereoselective Synthesis

Background:

• Transannular reactions are crucial for constructing complex molecular architectures.
• Stereochemical control in macrocyclization remains a significant challenge in organic synthesis.

Purpose of the Study:

• To explore a transannular Michael reaction cascade for stereoselective synthesis of polycyclic systems.
• To investigate the influence of stereochemistry in macrocyclic bis-enones on cyclization efficiency and diastereoselectivity.

Main Methods:

• Systematic exploration of a transannular Michael reaction cascade.
• Synthesis of 14-membered macrocyclic lactones with varying E/Z configurations of 1,7-bis-enones.
• Comparative analysis with transannular Diels-Alder reactions.

Main Results:

• High efficiency and excellent diastereoselectivity were achieved for E,Z- and E,E-1,7-bis-enones.
• Z,E- and Z,Z-macrocyclic lactones did not undergo cyclization under the tested conditions.
• Stereochemical outcomes were compared to transannular Diels-Alder reactions, revealing subtle differences.

Conclusions:

• The transannular Michael reaction cascade is a viable and stereoselective method for polycyclic system synthesis.
• The stereochemistry of the macrocyclic lactone significantly dictates the success of the transannular cyclization.
• Developed an acyl ketene approach for macrocyclic lactone synthesis and evaluated intramolecular Reformatsky reactions.