Eremophilane synthesis

This reaction was used to prepare an intermediate suitable for synthesis of the sesquiterpenes a- and p-eremophilane and related structures.306... 

This Sakurai reaction has been used for a stereoselective synthesis of nootkatone (2),4 an eremophilane sesquiterpene. Thus the trienone 1 cyclizes to 2 at 0° in the presence of C2H5A1C12 in 50% yield. TiCl4 and BF3 0(C2H5)2 are less effective catalysts (28% and 23% yields of 2). 

A second stereoselective total synthesis of ( )-eremophilone (243) has been accomplished using 7-epinootkatone (242) as intermediate.109 The latter compound was synthesized from (—)-/3-pinene (241) by modification of the published procedure"0 and subsequently converted into eremophilone (243) by the series of functional-group transformations shown in Scheme 30. A mycotoxin isolated from Penicillium roqueforti has been assigned the highly oxygenated eremophilane structure (244) on the basis of chemical and spectroscopic evidence."1 The structure and... 

Both (+)-nootkatone (566) and its (+)-4-isomer (565) have been synthesized from (+)-nopinone (564) (Scheme 69). ° On the other hand, Hiyama et have used a completely different approach for the synthesis of nootkatone (566) (Scheme 70) which involves as a key step the acid-induced cyclopentenone annulation. In an alternative route to eremophilane and valencane sesquiterpenes, NM et have used a stereoselective intramolecular Diels-Alder... 

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). 

In a recent synthesis of the eremophilane-type fukinone (6) Marshall and Cohen7 have also made use of the conjugate addition of dimethylcopperlithium. Reaction of the aj3-unsaturated ketone (4) with the reagent gives (5), which has the desired stereochemistry shown. The product was transformed into fukinone (6) in about ten steps. 

Finder and Torrencehave published the full details of their synthesis of fukinone (275). This paper also describes the synthesis of (-I-)-hydroxyeremo-philone (276). A number of new eremophilane sesquiterpenoids have been... 

Five trinor-eremophilane substances were identified by NMR experiments and, when necessary, by chemical conversions dendryphiellin A (52), a colorless oil of high optical activity [91], dendryphiellin A1 (56) [92] and dendryphiellins B (53), C (54) and D (55) [93]. TTiese substances are all esterified by dendryphiellic acids, derivatives of a C9 carboxylic acid, which can be considered as degraded monoterpenes or branched Cs-acetogenins, Dendryphiellic acids A (57) and B (58) have also been found in free state [88], as well as the monoglyceryl ester of dendryphiellic acid A (59) [92]. The synthesis of dendryphiellic acid A [93] has been performed, as well as that of its monoglyceryl ester [92]. 

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

Thiols and thioethers are the most commonly encountered sulphur derivatives which can be directly reduced to alkanes. For this purpose, Raney Ni has been traditionally used. An example of its use is the synthesis of let- and 7j5-eremophilanes from a tricyclic thiophene precursor (equation 29) However, more recently nickel complex reducing agents ( NiCRA ) have been profitably and effectively used for this purpose, as indicated by the reduction of dodecanethiol to dodecane (equation 30)". Similarly, nickelocene in the presence of LAH has been used to effect desulphurization of thiols . A combination of NaEtaBH and FeCl2 also achieves the thiol-to-alkane transformation quite satisfactorily The increasing utility of nickel boride has also been exploited for the transformation of sulphides to alkanes as indicated in equation 31. ... 

Several papers have concerned syntheses of terpenoids. The skeleton of sesquiterpenes such as eremophilane has been constructed by Naf etal. from the dienone (45), and Taber and Gunn have described a synthesis of ( )-torreyol (47) as outlined from the enone (46). Wilson and Mao have provided a further paper on their use of the intramolecular Diels-Alder reaction in the synthesis of diterpenes. 

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. 

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