Assembling the Methanoindene Cage of Phragmalin-Type Natural Products.

Phragmalin-type limonoids are highly complex natural products based on an unusual octahydro-1-2,4-methanoindene cage. The absence of feasible routes to sufficiently functionalized methanoindene cage building blocks impedes the total synthesis of these natural products. We have developed a short and robust route to methanoindene cage compounds from the Hajos-Parrish ketone (HPK). Several stereoselective modifications of the HPK provided a substrate that underwent aldol reaction as a key step for the cage formation.