Palladium-mediated reductive coupling, a stereoselective approach to the 8-dehydropumiliotoxin skeleton

Reductive cyclisation of an E-vinyl bromide with an allylic acetate proceeds under palladium catalysis to give the 8-dehydropumiliotoxin skeleton, a potential advanced precursor to 8-deoxypumiliotoxin alkaloids. Control of the stereochemistry of the E-vinyl bromide precursor is achieved readily using the Kogen or Bruckner bromophosphonate reagents and the reductive cyclisation proceeds with retention of the vinyl bromide stereochemistry. The mechanism for the cyclisation involves an in situ conversion of the allylic acetate to an allyl stannane followed by an intramolecular Stille-type coupling.