Bergamotene
( 2) has been synthesized in five steps from geranylacetone using intramolecular ketene-olefin cycloaddition as a key step.
We have recently completed a synthesis of retigeranic acid (L )l in which the pentacyclic system was generated by intramolecular cycloaddition of the ketene2 (derived from the reaction of the corresponding acid chloride with triethylamine) to form the cyclobutanonez. 2 1 2 3
The intramolecular ketene-olefin reaction occurred smoothly at 23" in 5 min to produce selectively cyclobutanone 2 in 80% isolated yield. The intramolecular ketene-olefm cycloaddition reaction has also been studied in these laboratories with a variety of substrates in conjunction with other synthetic targets. In some cases fused-ring cyclobutsnones were obtained (as forz) but in others I, S-bridged cyclobutanone structures were isolated. The literature also records the formation of both fused and bridged cyclobutanones from internal ketene-olefin reactions. 2
The problem of predicting the positional selectivity ("regioselectivity") of the internal ketene-olefin cycloaddition, which is central to the effective use of this process in the synthesis of complex molecules, is strongly linked to the question of mechanism, a matter that is far thorn settled. A key point is the extent to which the cycloaddition involves the simultaneous formation of the two new bonds. Although synchronous pericyclic mechanisms have a substantial following, 3 there are data which together make a reasonable case for lack of concert, and specifically for a transition state in which bonding between the ketenic carbonyl carbon and one of the olefinic carbons (the most nucleophilic) is considerably advanced over the development of the second bond. 4
In our experience the asynchronous picture provides a more useful model for predicting the course of intramolecular ketene-olefm cycloaddition than do any of the synchronous