Synthesis of the Major Pheromonal Component of the Monarch Butterfly (Danaus plexippus) via Palladium-Catalyzed 1,4-Functionalization of Isoprene

Article abstract of DOI:10.1021/jo00170a013

4-Chloroprenyl acetate (2), regioselectively prepared by palladium(II)-catalyzed 1,4-acetoxychlorination of isoprene, was selectively functionalized in the 1- and 4-positions to afford 6, which is readily transformed to the dimethyl ester of the pheromone (E,E)-3,7-dimethyldeca-2,6-diene-1,10-dioic acid (1a) of the Monarch butterfly.The allylic chloro group in 2 was chemoselectively substituted with sodium dimethyl malonate (classically or with palladium(0) catalysis) without affecting the allylic acetoxy group, which subsequently was replaced with sodium methyl acetoacetate using palladium(0) catalysis to give 5.The configuration of the double bond in 5 is >95percent E when triphenylphosphine is used as ligand.A double alkylation of 2 to 5 can also be performed as a one-pot sequence.Selective double decarboxylation of 5 gave methyl (E)-4-methyl-8-oxo-4-nonenoate (6) in 35 percent overall yield from isoprene.Transformation of 6 to the dimethyl ester of 1 has been described elsewhere.