Synthesis of the major pheromonal component of the Monarch butterfly (Danaus plexippus) via palladium-catalyzed 1,4-functionalization of isoprene

Abstract

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)-3,7-dimethyldeca-2,6-diene-l,10-dioic acid (la) of the Monarch butterfly. The allylic chloro group in 2 was chemoselectively substituted with sodium dimethyl malonate (classically or with palladium(O) 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 >95% 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 (£)-4-methyl-8-oxo-4-nonenoate (6) in 35% overall yield from isoprene. Transformation of 6 to the dimethyl ester of 1 has been described elsewhere.

Synthesis of Dimethyl Gloiosiphone A by Way of Palladium-Catalyzed Domino Cyclization

“…It is theoretically essential to add 4 equiv of NaH and 9 to complete the second allylation and to consume remaining 7 . Although it was necessary to add an additional amount of the palladium catalyst to complete the second allylation, the bromo group in 9 was selectively displaced by forming a π-allylpalladium intermediate to provide ( E )- 5 in 74% overall yield . The product 5 was isolated by silica gel column chromatography, whereas the diallylation product of 7 with 9 was also obtained.…”

Total Synthesis of (+)-Brefeldin A

“…The use of a stronger base such as DBU provided lower selectivity (entry 2). In light of the result that the reaction rate for Pd(PPh 3 ) 4 is slower than that for Pd(dppe) 2 , we attempted the cyclization of 5 in the presence of Pd(PPh 3 ) 4 /DBU. To our delight, the cyclization of 5 under these conditions afforded the bicyclic lactone 18 in an excellent yield, with no detection of the ( Z )-isomer 19 .…”

The Use of Sulfonyl 1,3-Dienes in Organic Synthesis

“…The butadiene sulfone 142 was transformed into a key intermediate for the synthesis of the Monarch butterfly pheromone. Michael addition, selective alkylation, and regioselective palladium-catalyzed allylic substitution afforded key intermediate 154 , which has been previously transformed into the pheromone . The sequence in Scheme demonstrates the efficiency of the principle shown in Scheme .…”