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 (kH/kD > 2), while the amines allow formation of a cyclohexenyl cation in chloroform to
lead to E1 as well as SN1 reactions (kH/kD ≈ 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.