Pergamon 0040-4039(94)02158-9 Tetrahedron Letters, Vol. 36, No. 1, pp. 15-18, 1995 Elsevier Science Ltd Printed in Great Britain 0040-4039/95 $9.50+0.00 Synthesis of the Sesquiterpene (+)-Ceratopicanol: Use of Radicals Derived from Epoxides Derrick L. J. Clive* and Steven R. Magnuson Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2 Summary: The sesquiterpene (__)-ceratopicanol [(_+)-1] was synthesized by a route based on Claisen rearrangement (7 --* 8) and radical cyclization (16~, 16[~ --* 170t, 17~). Certain limitations on vinyl radical cyclization were observed, and so the required radical was generated by titanium-induced opening of an epoxide. Ceratopicanol (1) 1 has a noteworthy place in biogenetic theory as its structure represents evidence for generation in vivo of carbonium ion 2 -- a species suggested2 to be a precursor of hirsutene and related natural products. We report the synthesis 3 of (+)-1 by a route that involves radical cyclization. Several of our experiments have exposed some limitations to certain types of radical closure. Enone 3 (Scheme 1), readily available by a reported method,4 was reduced (3 --~ 4; DIBAL, 89%), and Mitsunobu inversion under carefully controlled conditions5 (Ph3P, C1CH2CO2H, DEAD; LiA1H4; 58% overall), then gave the exo alcohol 5. This was converted successively into vinyl ether 7, then the product of Claisen rearrangement 8 and, finally, the reduction product 9. These transformations were best done (73% overall) by treating 5 with phenyl vinyl sulfoxide (5 --~ 6) and heating the product (150°C). 6 Under these conditions 7 was generated and it rearranged in situ to 8, which was reduced (8 --* 9; LiA1H4) without purification. Alcohol 9 was converted efficiently into bromide 10 (Ph3P, CBr4; 94%), and the bromine was then displaced (10 --~ 11) with lithium trimethylsilylacetylide. Exposure of 11 (which was not isolated) to 1 M methanolic sodium hydroxide gave the key acetylene 12 (94% from 10). When this compound was treated in refluxing benzene with Bu3SnH (0.01-0.07 M), in the presence of AIBN, the intermediate vinyl radical 13 was formed, but it gave 14, 7 the formal result of 6-endo trigonal closure. None of the product of the desired 5-exo closure, which we had observed as the exclusive pathway in model studies, 8 was isolated. Use of a higher stannane concentration (1.1 M) again led to 14, and hydrostannylation of the triple bond now became a serious competing reaction; consequently, we were unable to establish if the observed product is the result of initial 5- exo cyclization (13 --) 13'), followed by rearrangement (13' --* 13" ~ 14). 9 If the rate of hydrogen abstraction by the initial (hindered) radical (from 5-exo closure) is slow, the rearrangement (13' --~ 13" ~ 14) need not be unusually fast, but the possibility remains that formation of 14 is an example of kinetically preferred 15