Cyclization of geraniol

Scheme 33 Mechanistic studies on the PET-sensitized cyclization of geraniol.

Figure 1.14 a Equation for the cyclization of geraniol, and b possible mechanism in the presence of zeolite Y, a solid acid catalyst that has both Bronsted and Lewis acid sites. 

R = vinyl or ethynyl) predominates (c/. Vol. 1, p. 36 Vol. 2, p. 35). Base treatment of a 2-alkoxypyridinium tosylate of nerol gives expected e.g. limonene 82%) cyclic hydrocarbons whereas the corresponding geraniol salt yields similar amounts of cyclic and acyclic hydrocarbons. SnCU-catalysed cyclization of the N-benzylimine derived from R-(+)-citronellal yields the expected menthylamines after catalytic hydrogenation. ... 

Silver(I) catalyzed cyclizations of allenic alcohols (202) lead to 2,5-dihydrofurans (203) (79S743), whilst another mild method for the synthesis of tetrahydrofurans is the intramolecular oxymercuration-demercuration process. Geraniol, when treated with mer-cury(II) acetate and subsequently with sodium borohydride, gave a tetrahydrofuran. 

Exercise 30-5 a. Nerol and geraniol cyclize under the influence of acid to yield a-terpineol. How could the relative ease of cyclization of these alcohols, coupled with other reactions, be used to establish the configurations atthe double bond of geraniol, nerol, geranial, and neral Write a mechanism for the cyclizations. 

In a subsequent study, however, Whittaker and co-workers803 showed that the product formed from geraniol, in fact, is the isomeric bicychc ether 198. It was also shown that cyclization of citronellal in HSO3F— SO2 at 78°C affords pulegol and neoisopulegol that is, the transformation parallels closely the reaction in normal acids.804... 

The same group has further shown that the alkenyl double bond geometry of geraniol- as well as nerol-derived ketones 41 and 43 remains unaffected during the photocyclizations. This suggests that the rate of cyclization is much higher than the rotation about the double bond in the allylic radical center of the biradical (Scheme 8.12). 

Weng, H., Scarlata, C., and Roth, H.D. (1996) Electron transfer photochemistry of geraniol and (E, E)-farnesol. A novel tandem , 1,5-cyclization, intramolecular capture. Journal of the American Chemical Society, 118, 10947-10953. 

This reaction was used for a synthesis of the seven-membered cyclic terpene karahan-aenol (3) from the methyl ether (2) of geraniol by an electrophilic cyclization of an allylsilane.3... 

The coupling reaction of epoxide 69 with the anion derived from the allyl sulfide 57, a system derived from geraniol, was accomplished in a 99% yield by employing 4 equivalents of the anion (Scheme 13). Protection of the alcohol as the MOM ether (95%), followed by debenzylation and removal of the phenylthio group under Birch conditions (76%) gave diene 70. Vanadium catalyzed oxidation and spontaneous cyclization of 70 imder acidic conditions afforded a diastereomeric mixture of tetraols 71 and 72 in 61% and 14% yields, respectively. 

There are many examples of such reactivity and some of these have been reviewed by Roth and coworkers, a research group that is extremely active in this area. An example that is typical of the processes encountered involves the cyclization of the diene geraniol (1). In this case the sensitizer is 9,10-dicyanoanthracene (DCA) and the reactions are carried out in methylene chloride. The authors state that a contact radical-ion parr is involved, i.e. the radical cation of the diene is in close proximity to the radical anion of the DCA. Reaction within this yields the cyclopentane derivatives 2 and 3 in the yields shown. The ring formation is the result of a five centre CC cyclization within the radical cation of 1. When a more powerful oxidant such as p-dicyanobenzene is used as the sensitizer in acetonitrile as solvent, separated radical-ion pairs are involved. This leads to intramolecular trapping and the formation of the bicyclic ethers 4 and 5 . The bicyclic ether incorporates an aryl group by reaction of the radical cation of the diene with the radical anion of the sensitizer (DCB). This type of reactivity is referred to later. Other naturally occurring compounds such as (/fj-f-bj-a-terpineol (6) and (R)-(- -)-limonene (7)... 

Many hydroxylated linalools [including compounds 105, 106, 108, and 110, both (Z)- and ( )-isomers], as well as the epoxides of both furanoid (109) and pyranoid (see section on pyrans) linalyl oxides, have been identified in papaya fruit (Carica papaya). At the same time, the first reported occurrence of die two linalool epoxides (112) in nature was made. These epoxides are well known to be unstable and easily cyclized (see Vol. 2, p. 165) and have been made by careful peracid oxidation of linalool. An interesting new method has now been described. While the vanadium- or titanium-catalyzed epoxidation of geraniol (25) gave the 2,3-epoxide (see above), as does molybdenum-catalyzed epoxidation with hydrogen peroxide, the epoxidation of linalool (28) with molybdenum or tungsten peroxo complexes and hydrogen peroxide led, by reaction on the 6,7-double bond, to 112. ... 

The previously reported biogenetic-type cyclization of nerol and geraniol to limonene using 2-fluoropyridinium salts has been extended to the sesquiter-penoid area. Thus treatment of cw,rran5-farnesol (77) with 2-fluoropyridinium (74), 2-fluorobenzothiazolium (75), or 2-chlorobenzothiazolium (76) salts resulted in the formation of a-bisabolene (78) and y-bisabolene (79) in 55—75% yield. 

When geraniol reacts with phenols in the presence of acid, the common products are usually cyclized the use of 1 % oxalic acid has now been found to minimize cyclization in the reaction between orcinol and geraniol. Nerol has been labelled with deuterium in various positions [a, b, c, and d in (32)] and then converted into the chloride (33). Kinetic isotope effects on hydrolysis of (33) were measured, and 7r-participation in the cationic intermediate (34) leading to the cyclized terpinyl derivatives is discussed. Schwartz and Dunn proposed to use the complex (35), from geranyl methyl ether, as a model for a farnesol cyclization. They were not able to isolate this complex (although there was some evidence for its formation), the main complex (36%) being a dimeric a-complex (36), together with 39 % of the ketone (37), but no cyclized material. The cyclization of the acid chloride (38) to menthone and the C9 hydrocarbon (39) with tributyltin hydride, and also the optimum conditions for the cyclization of (-i-)-citronellal... 

CycUzatiou of geraniol. Treatment of geraniol (1) with this salt in CH2CI2 at 20° for 2 hours gives three new products (2), (3), and (4) in a total yield of 91%. The first two products possess the iridoid carbon skeleton. Cyclization to... 

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