Humulene transannular cyclization

A quite detailed review of transannular cyclizations was published201 wherein their important role in biomimetic syntheses of sesquiterpenes as well as explanation of the biogenetic formation of the polycyclic natural compounds from their monocyclic precursors is discussed. The great significance of these transformations for the synthesis of natural products is also emphasized in a series of reviews which describe the cyclizations to form terpene derivatives, e.g., of the germacrane and humulene systems202-206. 

Two transannular cyclizations have been reported which lead to isomers of 677. Thus, treatment of 677 or 678 with boron trifluoride etherate gives rise to capnellene (679) Also, conversion of humulene 6,7-oxide (680) to tricyclic epoxide 681 has provided the opportunity for trimethylsilyl triftate-promoted... 

Finally, transannular cyclization involving the A > - rather than the A -double bond in humulene-4,S-epoxide (150) can be achieved by first converting (150) to the corresponding aldehyde (159). Treatment of (159) with TMSOTf is then shown to lead to the fused S,7-ring system (160) in good yield (equation... 

When the substituent in 10 at C2 is a carboxaldehyde group, i.e. 10b, this cationic cyclopropana-tion reaction was accompanied by transannular cyclization to form a mixture of regiomeric olefins 12b. However, a selective reaction occurred with 10a on silylation with trimethylsilyl triflate in toluene at — 20 °C and subsequent desilylation with potassium fluoride in methanol a mixture of olefins 12a was obtained in 80% yield. Applying these conditions to 10b did not lead to 12 b. Instead, efficient transannular cyclization took place to form the 3,6-secoprotoil-ludane system. These reactions are examples of a regio- and stereoselective transformation of the humulene skeleton into cyclohumulanoids. 

Sesquiterpenes with eleven carbon atoms in the ring, for example humulene, have been subjected to electrophilic reactions providing products of transannular cyclization. 

Other examples of cyclization reactions involving alkenyl groups are the formation of the pentacyclic ether (133) from the BF3 OEt2-catalysed rearrangement of (132) and the transannular cyclization of humulene 9,10-oxide (134) to (135) (70%) in BF3 OEt2-acetic anhydride. ... 

Shirahama H, Hayano K, Kanemoto Y, Misumi S, Ohtsuka T, Hashiba N, Furusaki A, Murata S, Noyori R, Matsumoto T. Conformationally selective transannular cyclizations of humulene 9,10-epoxide. Synthesis of the two skeletally different cyclohumulanoids dl-bicyclohumulenone and dl-africanol. Tetrahedron Lett. 1980 21 4835-4838. 

When the C1-C2 double bond is deactivated, for instance by oxidation of the methyl group to an aldehyde group as in 11, opening of the oxirane ring by trimethylsilyl triflate provided a homoallyl carbenium ion which then underwent transannular Ti-cyclization but with participation of the C8-C9 double bond leading to a mixture of secoprotoilludane derivatives 12 and 13. In this case the rearrangement took place from a different C-C conformation, where in an intermediate step an additional Z/ isomerization of the C1-C2 double bond occurred. Reaction of the 8,9-epoxide of humulene with tin(IV) chloride led initially to formation of a cationic center at C9, but internal 7r-cyclization yielded an alcohol with a hydroazulene structure. ... 

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