Geranyl cation

Figure 2.10 shows some of the pathways that are possible with the 2,3-bond in the cis form and when the initial closure occurs at the 6,7-bond. This ring closure resembles the cyclisation of the geranyl cation to the /7-menthane skeleton, and the product, the bisabolane skeleton, similarly resembles a p-menthane skeleton, which has been extended by addition of an isoprene unit to its isopropyl tail. Elimination of a proton from this bisabolyl carbocation, or its trapping by a nucleophile, will lead to a sesquiterpenoid of the bisabolane family. However, there is a number of possibilities for further skeletal rearrangement, three of which are shown in Figure 2.10. 

Mash, E. A., G. M. Gurria, and C. D. Poulter, Famesylpyrophos-phate synthetase. Evidence for a rigid geranyl cation-pyrophosphate anion pair, J. Am. Chem. Soc., 103, 3927-3929 (1981). 

Besides a simple ionization-deprotonation process to the acyclic monoterpenes, GPP can also undergo cyclization reactions. The direct Markovnikov-type 1,6-cyclization of the ( )-configured geranyl cation by attack of the C6-C7 double bond at the cationic center is impossible since this would give a hypothetical ( )-cyclohexene product. Therefore, the isomerization of GPP via the geranyl cation to linalyl diphosphate (LPP) prior to cyclization is required (Scheme 87.15). The possible free rotation of the vinyl group into a cisoid conformation privileges... 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

An exactly analogous process can then occur, in which geranyl diphosphate provides the allylic cation, and a further molecule of isopentenyl diphosphate adds on, giving farnesyl diphosphate this can subsequently yield geranylgeranyl diphosphate. 

The compounds geranyl diphosphate, farnesyl diphosphate, and geranylgeranyl diphosphate are biochemical precursors of monoterpenes, sesquiterpenes, and diterpenes respectively, and virtually all subsequent modifications of these precursors involve initial formation of an allylic cation through loss of diphosphate as the leaving group. 

Before cyclization can occur, however, there has to be a change in stereochemistry at the 2,3-double bond, from E in geranyl diphosphate to Z, as in neryl diphosphate. It should be reasonably clear that geranyl diphosphate cannot possibly cyclize to a six-membered ring, since the carbon atoms that need to bond are not close enough to each other. The change in stereochemistry is achieved through allylic cations and linalyl diphosphate (see Box 6.4). 

Myrcenol can be prepared by treating myrcene with diethylamine to give a mixture of geranyl- and neryldiethylamine. These compounds are hydrated with a dilute acid to the corresponding hydroxydiethylamines. Deamination to myrcenol is effected by using a palladium-phosphine-cation complex as a catalyst [47]. 

In the presence of a cationic Rh[((/ )-binap)(cod)] complex, geranyl or neryl amides isomerize slowly to give a mixture of the corresponding enamide and dienamide (Scheme 20) (2). The optical purity of the chiral enamide is high, but the chemical yield is low. Certain cyclic allylic amides give the enamide isomers in a high ee. With a DIOP-Rh catalyst, prochiral allylic alcohols are converted to optically active aldehydes with low ee (31). 

As is indicated in Fig. 22-3, the same intermediate cation can yield a variety of end products. For example, pure geranyl diphosphate pinene cyclase catalyzes formation of several other terpenes in addition to a-pinene.89 Another aspect of terpene synthesis is that insects may convert a plant terpene into new compounds for their own use. For example, myrcene, which is present in pine trees, is converted by bark beetles to ipsenol (Fig. 22-3), a compound that acts as an aggregation pheromone.90... 

Photoproducts consistent with cationic reactive intermediates are also formed in the singlet excited state reaction of the allylic iodides geranyl and neryl iodide in n-hexane (equation 24)127. The favourable 2-Z geometry in neryl iodide leads to a larger proportion of the intramolecular alkylation product compared to the 1,4-HI elimination. Use of tetrahydrofuran instead of n-hexane promotes the formation of the cyclization products127, and so does the presence of Cu(I)57, which probably acts as a template. 

The metabolism of 7-endo-fenchol to ci-fenchone in fennel has been studied in quite some detail by Croteau and co-workers (Croteau and Felton, 1980). Croteau et al. (1980a) later reported a soluble enzyme preparation from the leaves of fennel which catalysed the cation-dependent cyclization of both geranyl pyrophosphate and neryl pyrophosphate to the bicyclic rearranged monoterpene 1-enc/o-fenchol. Croteau et al. (1980b) found that (+)-(lS)-fenchone, an irregular bicyclic monoterpene ketone thought to be derived... 

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