A series of derivatives from caryophyllene oxide have been prepared in enantiomerically pure form, including bicyclic, tricyclic and tetracyclic sesquiterpenes and sesquiterpenoids.
A key intermediate is the unsaturated, chiral (pro lS,82)-bridgehead carbocation 5 and its monobrominated derivative Sa. Caryophyllene (1) and its oxide 2 are naturally occurring sesquiterpenes which have fascinated organic chemists for a long time. Owing to the presence of the strained, frans-fused four-membeted ring, the conformationally mobile nine-membered ring and the highly reactive truns double bond, 1 and its derivatives enter into a wide variety of unusual transformations and deep-seated marrangements.'~ Caryophyllene derivatives containing osmophoric groups are also important in perfumery. For example, allylic alcohol 3 described below has a pleasant ambergris note.' The 5-methyl ketone derivative,4 which has been prepared from caryophyllene and acetyl tetrafluoroborate by an ene reaction,5 is commercially available under the name of [email protected] We here report new facets of caryophyllene chemistry, tesulting from the synthesis of the tricyclic [6.3.2.02*5] skeleton from caryophyllene oxide 2 in three stages. Results. Base-induced (LDA) opening of caryophyllene oxide 2 in tefiuxing THF gave allylic alcohol 3 in a clean mgio-and sterecselective reaction in 92% isolated yield. A low temperature mesylation afforded sensitive mesylate 4 (77%, 12.7 g), which was isolated and crystallized from Et20/PE (2: 1) at -20 0C6s7 Scheme 1.