SYNTHESIS OF (E,E)-GERMACRANE SESQUITERPENE ALCOHOLS VIA ENOLATE-ASSISTED 1,4-FRAGMENTATION

An efficient method has been developed for the synthesis of (E,E)-germ acrane sesquiterpene alcohols, The key step in these syntheses involve s the enolate-assisted 1,4-fragmentation of properly functionalized pe rhydro-1-naphthalenecarboxaldehydes with 1 equiv of sodium tert-amylat e as base, to give the corresponding (E,E)-germacrane aldehydes. These aldehydes are not very stable, and in situ reduction of the aldehyde function with Red-Al is required to obtain high yields of the desired germacrane alcohols. This procedure has led to the successful synthesi s of 15-hydroxygermacrene B (4) and 15-hydroxyhedycaryol (35) from the mesylates 6 and 33, respectively. When KHMDS is used instead of sodiu m tert-amylate in the fragmentation reaction of 6, isomerization of th e initially formed C(4)-C(5) E double bond cannot be avoided and resul ts, after in situ reduction with Red-Al, in the formation of the (E,Z) -germacrane alcohol 24. The 15-hydroxg-(E,E)-germacranes are excellent starting materials for the selective synthesis of the corresponding 4 ,5-epoxides, which in turn can perfectly well be used in studies on th e biomimetic formation of guaiane sesquiterpenes.