Total synthesis of (±)-nakafuran-8, a marine metabolite with antifeedant properties, based on formal bridgehead substitution of a bicyclo[2.2.2]oct-5-en-2-one system

Abstract

The first total synthesis of (±)-nakafuran-8, a furanosesquiterpene containing a bicyclo[4.2.2]decane skeleton, has been accomplished starting from 1-methoxy-4,5,8-endo-trimethylbicyclo[2.2.2]oct-5-en-2-one by a rearrangement strategy including the formal bridgehead substitution of this methoxy group by hydrogen on the basis of a pinacol-type rearrangement and the double ring-enlargement of this product to give 6,7,10-exo-trimethyl-bicyclo[4.2.2]dec-7-en-2-one via the bicyclo[3.2.2]non-6-en-2-one.