Bisabolanes, Sesquicamphanes, Santalanes, and Carotanes

Since a-bisabolol, in contrast to a-terpineol, has two asymmetric centers, the interesting question arises as to whether there is stereoselec-tively in the nucleophilic capture step. If there were a net anti addition of the electrophile (Ci) and the nucleophile (H2O) across the 6,7-double bond (as required for a configurationally stable non-classical carbonium ion intermediate), cis, trun -farnesol and trans-nttolidol should cyclize to one diastereomeric a-bisabolol (4R, 8R-55-OH and its enantiomer). Rittersdorf and Cramer have looked into the matter in a study of hydrolysis of cis, /ran -farnesyl phosphate (51-OP), trans-ntrolidyi phosphate (53-OP), and cw-nerolidyl phosphate (58-OP) (79). 

By means of gas chromatographic analysis they found that both diastereomers were present in comparable, but unequal, amounts. Although no independent evidence was available with which to assign the relative stereochemistries, they assumed that the diastereomer formed in excess would be the one resulting from an anti addition. The low stereoselectivity observed in these reactions proves that, if a transient non-classical carbonium ion is formed at all, it rapidly loses, for the most part, its stereochemical identity. The two diastereomeric bisabolols may then be formed by attack of water with comparable probability upon each of the diastereotopic faces of a planar, tertiary carbonium ion. 

As in the monoterpenes, no bicyclo[2.2.1]heptanes or bicyclo-[3.1.1]heptanes have as yet been found in the products from the cycliza-tion of farnesol or nerolidol or in the reactions of bisabolyl derivatives. However, with the more electrophilic double bond of an enol acetate, ring closure occurs as in the monoterpene series to give a mixture of the two stereoisomers which were converted onto campherenone and epi- 

It is not surprising that there seems to be no appropriate chemical precedent for the a n -Markovnikov cyclization to a seven-membered ring. On the contrary, the ring contraction of secondary carbonium ion (64) to the tertiary bisabolyl ion should be very rapid. However, the Prins-like conversion of the cycloheptenone (66) to the carotol ether (67) in the presence of stannic chloride mimics, to some degree, the second cyclization in the biogenesis of carotol 119). 

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