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 me tal-mediated carbocyclic ring forming reactions as key elements of our stra tegy (Scheme 1) is described. The highly functionalized cyclopentenone 4, t he product of a cobalt-mediated Pauson-Khand [2+2+1]cycloaddition, is the k ey 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. Conversi on of 17 to 1 was achieved in a minimal number of steps. The synthesis of a steriscanolide has been achieved in 19 steps and 12 % overall yield.