Rearrangement approaches to cyclic skeletons. Part 8. Total synthesis of (±)-nakafuran-8, a marine metabolite with antifeedant properties, on the basis of 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 by a rearrangement strategy starting from 8-endo-1-methoxy-4,5,8-trimethylbicyclo[2.2.2]oct-5-en-2-one. The methoxy group was replaced by hydrogen via(1) the pinacol-type rearrangement into the 1-methoxybicyclo[3.2.1-]oct-3-en-2-one, (2) DIBAL-H reduction, and (3) the pinacol-type rearrangement to give 8-endo-4,5,8-trimethylbicyclo[2.2.2]oct-5-en-2-one. The ring enlargement of this product gave 10-exo-6,7,10-trimethylbicyclo[4.2.2]dec-7-en-2-one, the key precursor of (±)-nakafuran-8, via the corresponding bicyclo[3.2.2]non-6-en-2-one.