TANDEM COPE-COPE REARRANGEMENTS

The first examples of tandem Cope-Cope rearrangements have been identified. When (1R*,4S*,6R*)1,6-divinylbicyclo[2.2.2]oct-2-ene (6) was rearranged thermally, smooth conversion to (1R*,8aS*)-1,2,3,5,6,8a-hexahydro-1-vinylnaphthalene (8) occurred. The mechanistic course of this isomerization was established by deuterium substitution as in 6-d(1) and by placement of a methoxyl group as in 14. The specific positioning of these labels in the corresponding products following upon thermal activation constitutes an especially stringent test of the operation of two [3,3] sigmatropic shifts in tandem. Since the intermediate in these reactions was not spectroscopically visible, the Cope-2 stage must be accelerated relative to the more energy-demanding Cope-1 lead-in step. This ordering is attributed to the kinetic benefits of strain release that materialize during passage to the final product. The discovery was also made that by positioning of an electron-rich aromatic ring at the distal carbon of the C(1) vinyl group, additional intramolecular acid-promoted cyclization can operate. The specific example is defined by the formation of 33. Finally, the consequences of anionic acceleration on the interruption of the tandem sigmatropic events were determined. The conversion of both 39 and 40 to their alkoxides did induce rearrangement at room temperature. The greater the concentration of negative charge on oxygen, the greater the kinetic acceleration and the greater the extent to which alternative pathways operate competitively.