Synthesis of the first "inside-outside" eight-membered ring via ring-closing metathesis: A total synthesis of (+/-)-asteriscanolide

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)(2)Cl2Ru(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.