R a R 1, 3 7, 9 8 2 OAc OH a OAc 10 4 CO 2 CH 3 CO 2 CH 3 + CO 2 R 11: R = CH 3 12: R = H 11, 12 a, b [bmim]BF 4 = N N BF 4 _ [bmim]PF 6 = N N PF 6 _ 5 6 1, 7: R = OH 3, 9: R = SO 2 Ph Superacid cyclization was demonstrated for the first time to be successful in those ionic liquids with functional groups that are stable in the reaction medium using aliphatic sesquiterpene derivatives as examples.

A mixture of (13E,17E)-12-phenylsulfonylbicyclogeranylfarnesol tetrahydropyranyl ether (8) and (13E,17E)-12-phenylsulfonylbicyclogeranylfarnesol (9) was formed by superacid low-temperature cyclization of exclusively trans-8-phenylsulfonylgeranylfarnesol tetrahydropyranyl ether (1). The structures of 8 and 9 were established using spectral data. The optically active form of 9 was also confirmed by retrosynthesis from (+)-sclareolide (10).Biomimetic superacid cyclization of terpenoids turned out to be an effective synthetic method for cyclic terpenoids [1][2][3][4][5][6][7][8]. We studied previously superacid cyclization of several α,ω-bifunctionalized mono-and sesquiterpenoids and showed that α,ω-geraniol derivatives gave cyclic products with the n-menthane structure [9] whereas α,ω-bifunctionalized sesquiterpenoids produced monocyclic derivatives of α-cyclogeraniol prenylated at the gem-dimethyl group, which were formed by initiation of the cyclization by protonation of the inner C-6-C-7 double bond [10]. Superacid cyclization of α,ω-bifunctionalized aliphatic (2E,6E,10E)-diterpenoids also begins with protonation of the inner C-10-C-11 double bond to form diterpenoids with the sacculatane carbon skeleton [11].Herein we report the synthesis and superacid cyclization of the tetrahydropyranyl (THP) ether of the bifunctionalized derivative of exlusively trans-geranylfarnesol in which the second functional group, phenylsulfonyl, is located in the middle of the aliphatic carbon chain of the sesquiterpenoid on C-8. We selected the phenylsulfonyl group because it is easy to insert in the necessary position on the carbon chain, is stable toward superacid, and can be replaced by other functional groups.The starting material for cyclization of the THP ether of exclusively trans-8-phenylsulfonylgeranylfarnesol (1) was prepared by etherification of exclusively trans-8-phenylsulfonylgeranylfarnesol (2) with dihydropyran (90% yield). Compound 2, in turn, was synthesized in 91% yield by addition of commercially available (2E,6E)-farnesylchloride (3) to 8-phenylsulfonylgeraniol (4), which was prepared from the known ω-hydroxygeranylacetate (5) [12]. Bromination of the last by phosphorus tribromide produced 8-bromogeranylacetate (6) in 70% yield. This reacted smoothly with sodium phenylsulfonate to give 8-phenylsulfonylgeranylacetate (7). Saponification of 7 with alcoholic base gave 8-phenylsulfonylgeraniol (4) (Scheme 1).Spectral and elemental analysis were used to find the structure of 2. Its PMR spectrum contained signals for 6 methyls on double bonds, 5 vinyl protons, and >C=CHCH 2 OH and >CHSO 2 Ph groups. Its 13 C NMR spectrum exhibited signals for 6 methyls on fully substituted C atoms, 8 methylenes, and 11 methines, 6 fully substituted C atoms, and 16 sp 2 -hybridized C atoms. Superacid cyclization of the THP ether of 1 by fluorosulfonic acid at -78°C in 2-nitropropane formed a mixture of compounds, from which column chromatography over silica gel isolated two pure compounds of different polarity. The PMR spectrum of the ...

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