Scalable Total Synthesis of Leucascandrolide A Macrolactone Using a Chiral Phosphoric Acid/CuX Combined Catalytic System

Abstract

A scalable total synthesis of leucascandrolide A macrolactone has been accomplished with a longest linear sequence of 17 steps from readily available feedstocks in 31.2% yield. The key steps in this synthesis are the enantioselective allylation reaction by chiral phosphoric acid (CPA)/CuBr cooperative catalysis and the diastereoselective catalytic crotylation in the presence of CPA with CuCl. These catalytic reactions can be performed on a gram scale to afford the desired products with excellent stereoselectivities.

Exploring a Non-Comfort Zone: Central Chirality-Generating Macrocyclizations

“…In addition, examples of disconnections guided by biosynthetic proposals are discussed separately. Notably, Mitsunobu macrocyclizations, intramolecular glycosylations, and other processes involving a stereoselective transformation over a preexisting stereogenic center are not included in this JOCSynopsis.…”