Elimination-addition mechanism for nucleophilic substitution reaction of cyclohexenyl iodonium salts and regioselectivity of nucleophilic addition to the cyclohexyne intermediate.
The reaction of 4-substituted cyclohex-1-enyl(phenyl)iodonium tetrafluoroborate with tetrabutylammonium acetate gives both the ipso and cine acetate-substitution products in aprotic solvents. The isomeric 5-substituted iodonium salt also gives the same mixture of the isomeric acetate products. The reaction is best explained by an elimination-addition mechanism with 4-substituted cyclohexyne as a common intermediate. The cyclohexyne formation was confirmed by deuterium labeling and trapping to lead to [4 + 2] cycloadducts and a platinum-cyclohexyne complex. Cyclohexyne can also be generated in the presence of some other mild bases such as fluoride ion, alkoxides, and amines, though amines are less effective bases for the elimination. Kinetic deuterium isotope effects show that the anionic bases induce the E2 elimination (k(H)/k(D) > 2), while the amines allow formation of a cyclohexenyl cation in chloroform to lead to E1 as well as S(N)1 reactions (k(H)/k(D) approximately 1). Bases are much less effective in methanol, and methoxide was the only base to efficiently afford the cyclohexyne intermediate. Nucleophiles react with the cyclohexyne to give regioisomeric products in the ratio dependent on the ring substituent. The observed regioselectivity of nucleophilic addition to substituted cyclohexynes is rationalized from calculated LUMO populations, which are governed by the bond angles at the acetylenic carbons: The less deformed carbon has a higher LUMO population and is preferentially attacked by the nucleophile.
Fujita
Morifumi
M
Graduate School of Material Science, Himeji Institute of Technology, University of Hyogo, Kohto, Kamigori, Hyogo 678-1297, Japan. fuji@sci.u-hyogo.ac.jp
Kim
Wan Hyeok
WH
Sakanishi
Yuichi
Y
Fujiwara
Koji
K
Hirayama
Sayaka
S
Okuyama
Tadashi
T
Ohki
Yasuhiro
Y
Tatsumi
Kazuyuki
K
Yoshioka
Yasunori
Y
D000085:Acetates / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry*; D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D003510:Cyclohexanes / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry; D007700:Kinetics; D015394:Molecular Structure; D009861:Onium Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D010880:Piperidines / Q000737:chemistry; D013237:Stereoisomerism
D000085:Acetates; D000475:Alkenes; D000480:Alkynes; D003510:Cyclohexanes; D009861:Onium Compounds; D010880:Piperidines; D003903:Deuterium