Caryophyllene rearrangement

By using betulin as substrate, some mechanistic studies were performed and it was demonstrated that these reactions are catalyzed by Brpnsted acid species generated in situ from the hydrolysis of Bi(0Tf)3-.vH20. This process was also applied to other terpenic compounds. The sesquiterpene ( )-caryophyllene oxide originated clov-2-en-9a-ol by a cariophyllene-clovane rearrangement (Scheme 41) whereas 3-oxo- l 8a-olean-28- l 3(3-olide was obtained from oleanonic acid (Scheme 42). With this triterpene derivative, only 28,13(3-lactonization occurred, with inversion of the configuration of the stereocenter at C18 [133],... 

Scheme 41 Bi(0Tf)3-xH20-catalyzed Wagner-Meerwein rearrangement of (—)-caryophyllene oxide...

Caryophyllene. (-)-Caryophyllene can be isolated from Indian turpentine and has been used to prepare a number of woody aroma products. The epoxides are produced by reaction with peracids. Acetylation of caryophyllene also gives a useful methyl ketone (180) (Fig. 8). Acid-catalyzed rearrangement of caryophyllene in the presence of acetic acid gives a mixture of esters, which are related to caryolan-l-ol and clovan-2-ol (181). 

Collado and co-workers made detailed studies of the chemistry of the sesquiter-penoid caryophyllene and its hydroxylated products including rearrangements in-duced by superacids. They have recently reported novel rearrangements of the sesquiterpenoid panasinsane derivatives 213 to provide three products and interpreted the transformations by the involvement of the common carbocationic intermediate 214 [Eq. (5.304)]. 

Though the rearrangement step transforms a stable tertiary cation into a less stable secondary cation, relief of strain in expansion from a four- to a five-membered ring makes the alkyl migration favourable. In 1964, E.J. Corey published a synthesis of the natural product a-caryophyllene alcohol that made use of a similar ring expansion. Notice the photochemical [2+2] cycloaddition (Chapter 35) in the synthesis of the starting material. 

Although isocomene (668), mentioned above, is included in this section it is likely that this hydrocarbon, together with modhephene (679), is derived from a caryophyllene-type precursor. Indeed one can conceive of a biogenetic pathway (Scheme 87) which encompasses both these compounds as well as botrydial (681), quadrone (682), and the recently isolated senoxydene (304). " To lend partial credence to this scheme is the fact that the hydrocarbon (680) is a product of acid-catalysed rearrangement of isocaryophyllene (678). ... 

The rearrangement of jS.y-epoxyketones with diethylamine has been examined under mild conditions. a,(3-Epoxyketosteroids undergo the Favorskii rearrangement." The rearrangement of three stereoisomers of caryophyllene ketooxirane has been followed in a tert-BuOH-HjO-KOH system. ... 

The ready availability of four-membered rings of defined stereochemistry from enone-alkene photocycloadditions has been the origin of several syntheses which employ Wagner-Meerwein rearrangements in subsequent steps. This is exemplified by a neat and very short synthesis of a-caryophyllene alcohol (40) from cyclopentene and 3-methylcyclohexenone which was described some years ago (see Scheme 15). The rearrangement in 40% sulfuric acid proceeded remarkably smoothly. A short synthesis of iso-comene (41 Scheme 16) also Illustrates this strategy... 

Caryophyllene is the main hydrocarbon component of clove oil, from which it is produced as a by-product of eugenol extraction. The endocyclic double bond of caryophyllene is highly strained and reacts readily with a variety of reagents. Usually both double bonds become involved in a trans-annular reaction, followed by rearrangements to give mixtures of polycyclic products. Some of these mixtures find use as woody ingredients in perfumes. Caryophyllene and two typical reaction products from it are shown in Scheme 4.29. 

Naya and Kotake, in an examination of Japanese hop oil, have isolated three humulane-type compounds, viz., humuladienone (161, R = Me), humulenone II (161,R = =CH2), and humulol (162), in addition to the tricyclic diol (163, R = OH), m.p. 207 °C. This diol has already been prepared in two different ways (a) Sutherland et treated humulene (164) with AT-bromosuccini-mide in aqueous acetone and converted the resultant bromohydrin (163, R = Br) to the diol (163, R = OH), m.p. 205—206 °C, by hydrolysis, (b) McKervey and Wright obtained the same diol, m.p. 201—203 °C, by acid-catalysed (20% sulphuric acid) rearrangement of humulene 1,2-epoxide (165), a known natural product. On the basis of these findings and the fact that both caryophyllene (166) and humulene can be derived from the above bromohydrin by two in vitro steps, McKervey and Wright postulated that humulene 1,2-epoxide may be involved in the biosynthesis of the tricyclic diol and caryophyllene. This postulate does not, however, readily accommodate the observed rotations of the relevant... 

The rearrangements of isocaryophyllene (7.138) are more straightforward than those of caryophyllene (7.163). It does produce neoclovene... 

This ring-expansion process is quite useful when applied to polycyclic systems. Corey treated 57 with 40% sulfuric acid and isolated the rearranged alcohol, a-caryophyllene alcohol (60). The initially formed cyclo-butylcarbinyl cation (58) rearranged to the cyclopentyl cation (59), which was trapped by water to give 60. 

Terpenoids with double bonds can undergo various rearrangement and transformations as well as oxidation reactions. Some reactions proceed easily others may be induced by acid, heat, or irradiation treatment. Some examples are given below p-Caryophyllene (P-caryophyllene) is oxidized when exposed to air, and after 5 weeks, nearly 50% of the original compound was consumed. The main oxidation product was caryophyllene oxide [40]. Limonene is easily oxidized to limonene... 

In dioxan-water containing 0.02 mol 1 perchloric acid, humulene is hydrated to humulol (256) which then rearranges to give a-caryophyllene alcohol (257 20—25 %) and a mixture of bicyclo[5,3,0]decenes (75 %) of which (258 90% of the mixture) is the major component. Mechanisms for these rearrangements were proposed based on... 

CHAlUHGtl Humulene and a-caryophyllene alcohol are terpene constituents of carnation extracts. The former is converted into the latter hy acid-catalyzed hydration in one step. Write a mechanism. (Hint The mechanism includes cation-induced double-bond isomerization, cyclizations, and rearrangements that may involve hydrogen and alkyl-group migrations. Two of the intermediates in the mechanistic sequence are shown five carbon atoms are identified by starts to help you track their positions through the process.)... 

Figure 10 Epoxidation of caryophyllene and rearrangement of the 4,5-epoxide by Chaetomium cochlioides.

---