Michael addition-elimination mechanism for nucleophilic substitution reaction of cycloalkenyl iodonium salts and selectivity of 1,2-hydrogen shift in cycloalkylidene intermediate.

Reactions of cyclohexenyl and cyclopentenyl iodonium salts with cyanide ion in chloroform give cyanide substitution products of allylic and vinylic forms. Deuterium-labeling experiments show that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt, followed by elimination of the iodonio group and 1,2-hydrogen shift in the 2-cyanocycloalkylidene intermediate. The hydrogen shift preferentially occurs from the methylene rather than the methine beta-position of the carbene, and the selectivity is rationalized by the DFT calculations. The Michael reaction was also observed in the reaction of cyclopentenyliodonium salt with acetate ion in chloroform. The vinylic substitution products are ascribed to the ligand-coupling (via lambda3-iodane) and elimination-addition (via cyclohexyne) pathways.

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.

Highly stereoselective protonation of the enolate of a bicyclic cycloheptatrienyl lactone occurs on the hindered face.

[reaction: see text] The H/D exchange of the lactone-fused cycloheptatriene 1 is over 1000 times faster than that of the epimer 2. Interconversion of 1 and 2 provides an equilibrium mixture of 1:0.7, showing a similar stability of the isomers. Protonation of the common enolate 7 occurs far more readily on the more hindered face. Cycloheptatrienide anion is bent and as stable as a divinylcarbanion.