Eremophilanes. rearrangement

In their synthesis of fukinone, Marshall and Cohen converted the known ene-ol (340) into (341) by acetylation, allylic oxidation, and conjugate methylation with dimethylcopperlithium. A Wolff-Kishner reduction of (341) followed by oxidation of the resultant alcohol and enol-acetylation yielded (342). The epoxide of (342) was thermolysed to give (343) which, on reaction with iso-propenyl-lithium and selective oxidation, gave the ketol (344) which was converted in two steps into fukinone (335). A number of sesquiterpenoids, e.g. fukinanolide (345), with the rearranged eremophilane skeleton viz. fukinane (346 R = Me) are known. Nay a and Kobayashi have now prepared this parent hydrocarbon by Raney nickel reduction of the thioacetal of fukinan-8-al (346 R = CHO). 

Full details of the synthesis of (+)-nootkatone (606) from (+)-nopinone (607) have been described. The rearranged eremophilane phenol cinalbicol (608) has also been synthesized. ... 

Of the rearranged eudesmanes, eremophilanes (216) are most prolific ( 150 derivatives). The subject was reviewed in 1977 (314). Two stereochemical classes, 239 and 240, have been recognized in principle, these are related to the eudesmane (222) and intermedeane types (225), respectively. The first member of this class to be characterized was eremophilone (241), which occurs in the wood oil of the Australian tree Eremophila mitchelli, along with other related compounds. This was the first terpene structure not consistent with the isoprene rule and Robinson (327) invoked a 1,2-methyl shift from a eudesmane precursor to rationalize this structure. (-)-Eremoligenol (242) is a component of roots of Ligularia fischeri, while isovalencenic acid (243) has been isolated from vetiver oil. (-h)-Nootkatone (244) was first isolated from the heartwood of Alaska-cedar... 

Several of the earlier syntheses of eremophilane sesquiterpenes have utilized the Robinson annelation reaction as a key step ". However, the synthesis of nootkatone outlined below is based on acid catalyzed rearrangement of the Diels-Alder adduct (B), directly available from a 1-methoxycyclohexa-l,4-diene (A), to a 4-substituted cyclohexenone which undergoes ring closure in formic acid to give the desired eremophilane skeleton. 

Dunham and Lawton have suggested an alternative biogenesis for the eremophilane sesquiterpenes via a series of four decalyl spiro rearrangements, a process which effectively shifts the position of the methyl group from one angular position to the other (238). This proposal has the disadvantage of requiring a cw-fused eudesmane precursor, a known (occidentalol), but rare stereochemical variant, and, at least in the case of capsidiol is excluded by recent biosynthetic results (229). 

---