Terpineol linalool cyclization

Arigoni and co-workers128 used isotopic labeling experiments to show that the cyclization of linalool to a-terpineol occurs at the center of the double bond rather than at its extremities. In principle, the intermediate cation 30 could adopt an elongated conformation 31 leading to 33 (which is not found) or the folded conformation 32, where attack of the carbocation at the center of the double bond gives the observed product 34. 

Three new monoterpenoid lactones, (28)—(30), isolated from the urine of koala bears fed on Eucalyptus punctata, appear to have arisen from the cyclization of carboxylic acids formed as hydrolysis products of glucuronide conjugates from the metabolism of a- and /3-pinenes.70 Linalool injected into various plant species has been claimed to be converted into a-terpineol and other monoterpenoids.71 However, direct interconversions cannot be inferred from this type of non-radioactive tracer study. The terpenoids alleged to be produced may well be stress metabolites or be formed b secondary processes that perturb the usual pattern of terpenoid formation. 

The one-pot epoxidation/cyclization of unsaturated terpene alcohols, for example linalool and a-terpineol, to mono- and bicyclic derivatives also required the catalysis of large-pore Ti,Al-P (Scheme 18.10) [93, 107]. 

The resorcin[4]arene capsule was shown to efficiently mimic enzymes when it came to these aspects, thanks to its abifity to stabilize the cationic allylic intermediate, limiting the attack from undesired nucleophiles and favoring the selective cyclization to certain products. In fact, it was observed that geranyl alcohol could be a suitable guest for the capsule that, in the presence of 10 mol% of capsule at 30°C, could be completely converted in 28 h with the initial formation of terpinene, linalool, and a-terpineol, all species derived from the selective formation of the intermediate carbocation. The two intermediate alcohols formed were further converted over time, giving rise to eucalyptol (Fig. 7.16a). Confirmation of the peculiar role played by the cavity of the... 

A remarkable feature of the cyclizations of linaloyl derivatives is the high stereoselectivity in the formation of a-terpineol. Thus, the hydrolysis of ( —) linaloyl phosphate (33-OP) affords (-h )-a-terpineol with an optical purity of 40% (79). The cyclization of linalool to optically active a-terpineol may also be carried out with sulfuric acid in acetic acid (81) and aqueous sulfuric acid (82). The a-terpinyl j9-nitrobenzoate produced in the hydrolysis of linaloyl /7-nitrobenzoate is obtained with an optical purity as high as 87% (80). These results require that cyclization occurs, at least in part, from an asymmetric transition state. 

The established stereochemical relationship between linalool and the derived a-terpineol (79, 80) is such that the departing hydroxyl group and the proton on the new asymmetric at C4 bear a syn relationship in the cyclization. Since both neryl and a-terpinyl / -nitrobenzoates are produced in relatively large amounts from internal return in the hydrolysis of 33-OPNB, the proposal was made that cyclization in this case occurs from an initially formed cisoid allylic cation />-nitrobenzoate ion pair (38) (80). 

---