Solvolysis of Caryophyllen-8β-yl Derivatives:  Biomimetic Rearrangement−Cyclization to 12-Nor-8α-presilphiperfolan-9β-ol

The solvolyses of caryophyllen-8β-yl p-nitrobenzoate (14-OpNB) and 15-norcaryophyllen-8β-yl tosylate (15-OTs) were investigated as potential model reactions for the biogenesis of the tricyclic presilphiperfolanol sesquiterpenes. Buffered solvolysis of 14-OpNB in 60% aqueous acetone at 125 °C afforded caryophyllene (3) as major product, accompanied by small amounts of caryophyllen-8β-ol (14-OH) and 5,8-cyclocaryophyllen-4α-ol (16). In contrast, 15-OTs underwent a stereospecific rearrangement−cyclization to 12-nor-8α-presilphiperfolan-9β-ol (17) upon solvolysis in 60% aqueous acetone at 75 °C. The structure and stereochemistry of this trans,cis,trans-tricyclo[6.2.1.05,11]undecane derivative were established by NMR correlation spectroscopy and X-ray crystallography. Two different mechanisms (paths A and B) for the conversion of 15-OTs to 17 by initial 1,2-migration of either the external or internal cyclobutane ring bonds (C10 and C1) followed by π−σ cyclization onto the trans double bond are discussed.