Total Synthesis Highlights

There were two remaining problems in the synthesis. The alkene of 2 had to be converted to the
methylated tertiary alcohol, and the ketone had to be elaborated to the ene diol. While seemingly
straightforward, the congested tricyclic skeleton of 2 made many common transformations
difficult. The solution to the former problem was found in the selective dipolar addition of
bromonitrile oxide. Reduction of the ketone then enabled HO-directed hydrogenation of the
alkene, that otherwise was resistant. Dehydration followed by reduction with LiAlH 4 gave the
desired methyl group bearing a primary amine, that was removed by free radical reduction of the
corresponding isonitrile, to give 12.
With 12 in hand, the end of the synthesis appeared to be in sight. In fact, the reduction of a variety
of oxidized intermediates proved difficult. In the end, a sequence that did not require reduction
proved effective. Dihydroxylation of 12 gave a diol, selective oxidation of which delivered the
α-hydroxy ketone 13. Formation of the trisylhydrazone followed by Shapiro reaction gave the
intermediate alkenyl anion, that was trapped with formaldehyde to give the long-sought Vinigrol
(3).
Vinigrol (3) produced by this sequence was racemic. The absolute configuration of the ring
system was set in the course of the Diels-Alder addition of 5 to 4. Use of a chiral catalyst in this
step could set the stage for an enantioselective synthesis of 3.
D. F. Taber, Org. Chem. Highlights 2010, September 6.
URL: http://www.organic-chemistry.org/Highlights/2010/06September.shtm