A Concise Total Synthesis of (−)‐Berkelic Acid. Issue 10 (18th January 2021) - Cheng, Hong‐Gang
Abstract: Reported here is a concise total synthesis of (−)‐berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa‐Michael cascade for the construction of the isochroman scaffold, a one‐pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late‐stage Ni‐catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations. Abstract : A concise total synthesis of (−)‐berkelic acid in eight linear steps was developed. This synthesis features a Catellani reaction/oxa‐Michael cascade for the construction of the isochroman scaffold, a one‐pot deprotection/spiroacetalization operation for the formation of tetracyclic core structure, and a late‐stage Ni‐catalyzed reductive coupling for the introduction of the lateral chain.