Longifolene reactions

Longifolene. There are at least four commercially important aroma chemicals made from (+)-1ongifo1ene and about thirteen products made from (-)-isolongifolene (90) (182). Acetoxymethyl longifolene or the formate are formed during the Prins reaction on (+)-1ongifo1ene. Saponification of the esters gives the useful perfumery alcohol (183) (Fig. 9). 

Longifolene has also been synthesized from ( ) Wieland-Miescher ketone by a series of reactions that feature an intramolecular enolate alkylation and ring expansion, as shown in Scheme 13.26. The starting material was converted to a dibromo ketone via the Mr-silyl enol ether in the first sequence of reactions. This intermediate underwent an intramolecular enolate alkylation to form the C(7)—C(10) bond. The ring expansion was then done by conversion of the ketone to a silyl enol ether, cyclopropanation, and treatment of the siloxycyclopropane with FeCl3. 

This chiral intermediate, when carried through the reaction sequence in Scheme 13.30, generated the enantiomer of natural longifolene. Thus D-proline would have to be used to generate the natural enantiomer. 

An enantiospecific synthesis of longifolene was done starting with camphor, a natural product available in enantiomerically pure form (Scheme 13.31) The tricyclic ring was formed in Step C by an intramolecular Mukaiyama reaction. The dimethyl Multistep Syntheses substituents were formed in Step E-l by hydrogenolysis of the cyclopropane ring. 

Another enantiospecific synthesis of longifolene shown in Scheme 13.32 used an intramolecular Diels-Alder reaction as a key step. An alcohol intermediate was resolved in sequence B by formation and separation of a menthyl carbonate. After oxidation, the dihydropyrone ring was introduced by 7-addition of the ester enolate of methyl 3-methylbutenoate, followed by cyclization. 

Fallis, in the synthesis of longifolene (53), a bridged sesquiterpene, performed the intramolecular cycloaddition of compound 51 as a key reaction in the construction of the bridged system (Scheme 9.13) [55]. 

Several papers on the chemistry of longifolene derivatives have been published. These include the conversion of the two half-esters (225) and (226) into the same olefinic ester (227) with Pb(OAc)4-Cu(OAc)2, the reaction of longifolene (228) with mercuric acetate followed by iodine chloride to give (229) and (230), and the reaction of longicyclene (231) with bromine in pyridine and iodine chloride-pyridine complex in acetic acid to yield (232) and (233) respectively. 

Structure V would be ideally constituted (see Vb) for the construction of the second C-C bond required by structure II. One major roadblock, however, is found at this point. It is the formation of a very unusual bridgehead carbo-cation (Via) that violates Bredt s rule. Nevertheless, caibenium ions at bridgeheads of polycyclic structures are well accepted reaction intermediates." Furthermore, structure VI, being an anti norbomenyl cation, benefits from the additional potential stabilization of its nonclassical caibenium ion character. It would not sit around long before water converted it to the longifolene precursor... 

In the synthesis of occidentalol (ref. 13), a eudesmane-type compound consisting of a cis-fused decalin containing a homoannular 1,3-diene system, dihydrocarvone was converted by a typical Robinson annellation reaction to the basic reguired bicyclic structural unit. (It is of interest that a related bicyclic methyldecalenone structure, the Wieland-Miescher ketone, has been employed for the synthesis of longifolene (ref.14), copaene (ref.15) and sativene (ref.16) by three totally different strategies outside the present concept of the semi-synthetic approach). 

Reactions similar to this type of fragmentation have been encountered by Sukh Dev in longifolene chemistry. One noteworthy feature of the fragmentation leading to (85) is Ae synperiplanar orientation... 

Substituted tetracyclo[5.4.0.0 . 0 ]undec-10-en-5-ones, e.g. 27, which can be made by intramolecular Diels-Alder cycloaddition reactions, offer potential synthetic entries to sinularene-type 28 and longifolene-type 29 natural products via reductive cleavage. ... 

Over the past 25 years longifolene (283) has been the focus of many aspects of chemical research—synthesis, molecular rearrangements, transannular reactions, and biosynthesis. All these and other details of longifolene chemistry have been thoroughly reviewed by Sukh Dev142 who himself has made many major contributions in this area of natural product chemistry. (+)-Longifolene can be converted into crystalline dilongifolylborane.143 This chiral dialkylborane can... 

Transannular reactions represent an interesting family of hydrogen transfer processes that can be applied for highly selective and efficient remote functionalization. For instance, Zard reported -functionalization in the longifolene series via Barton decarboxylation of isolongifolic acid (Scheme 21, Eq. 21.1) [97]. A spectacular regio-and stereoselective remote hydroxylation of bicyclic ketone is reported by Winkler... 

Longifolene [( + )-47] is a natural product from Indian terpentine oil and is commercially available so that chemical synthesis is unnecessary. On hydroboration with borane-dimethyl sulfide complex, diisolongifolylborane (48) is formed, a stable, isolable compound (for a detailed description, see ref 36). It has been utilized as achiral reagent in allyl transfer reactions (Section D.2.5.2.). 

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