Synthesis of the First "Inside-Outside" Eight-Membered Ring via Ring-Closing Metathesis: A Total Synthesis of (±)-Asteriscanolide

Abstract

A total synthesis of (±)-asteriscanolide which features two transition metal-mediated carbocyclic ring forming reactions as key elements of our strategy (Scheme 1) is described. The highly functionalized cyclopentenone 4, the product of a cobalt-mediated Pauson-Khand [2 + 2 + 1] cycloaddition, is the key starting point for the synthesis. Excellent regiocontrol was obtained in the intermolecular Pauson-Khand reaction. Further synthetic manipulations of 4 led to diene 16 which underwent ring-closing metathesis using (PPh3)2Cl2Ru(CHPh) to provide the desired "inside-outside" tricycle 17. Conversion of 17 to 1 was achieved in a minimal number of steps. The synthesis of asteriscanolide has been achieved in 19 steps and 12% overall yield.