TOTAL SYNTHESIS OF AVERMECTINS .1. ENANTIOSELECTIVE SYNTHESIS OF THE SOUTHERN PART USING A SEQUENTIAL DIECKMANN-FREE RADICAL CYCLIZATION APPROACH

A synthesis of the C1-C9 southern moiety of avermectins has been carri ed out in 13 steps using an asymmetric epoxidation reaction as the onl y source of optical activity. Starting from 6-methylhept-5-en-2-one an d tetrahydropyranyl propargyl ether, the key steps of the synthetic ro ute involved a Dieckmann reaction followed by a free radical cyclizati on for the construction of the benzofuran nucleus. The Bu3SnH-induced formation of the tetrahydrofuran ring cleanly delivered the E-vinyl st annane function required for the subsequent Stille's coupling reaction with the northern part of avermectins. The crucial DELTA3,4 non-conju gated double bond was smoothly created by elimination of an intermedia te tertiary hydroxyl group at C-4.