Catalytic dicyanative [4 + 2] cycloaddition triggered by cyanopalladation using ene-enynes and cyclic enynes with methyl acrylate.
Palladium-catalyzed dicyanative [4 + 2] cycloaddition using various ene-enynes was investigated. The key species in this process is a cyanoallene intermediate that is obtained by the cyanopalladation of conjugated enynes followed by 5-exo-cyclization. To achieve an efficient [4 + 2] cycloaddition reaction, both the smooth generation of this species and critical control of regioselectivity in the 6-endo-cyclization step are quite important. A study of the substrate scope revealed that the reaction is strongly affected by the steric bulk of the substituents on the enyne and alkene units and prefers to give trans-fused cycloadducts. The stereochemistry of olefins was reasonably transferred to the corresponding products. Further study proved that this transformation includes not a thermal [4 + 2] cycloaddition process via 1,2-dicyanoalkenes generated in situ but rather a palladium-mediated stepwise cyclization sequence to control a maximum of five contiguous stereogenic centers in a single operation. An intermolecular version using methyl acrylate with conjugated cyclic enynes and TMSCN also gave the corresponding [4 + 2] cycloadducts in a regioselective manner.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Shigeru
S
Arai
Yuka
Y
Koike
Hirohiko
H
Hada
Atsushi
A
Nishida
D000179:Acrylates / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
D000179:Acrylates; D000480:Alkynes; D009570:Nitriles; D010165:Palladium; C035956:methyl acrylate