Selectivity and Mechanism of Iridium-Catalyzed Cyclohexyl Methyl Ether Cleavage

Cationic
bis­(phosphine)iridium complexes are found to catalyze
the cleavage of cyclohexyl methyl ethers by triethylsilane. Selectivity
for C–O cleavage is determined by the relative rates of SN2 demethylation versus SN1 demethoxylation, with
the axial or equatorial disposition of the silyloxonium ion intermediate
acting as an important contributing factor. Modulation of the electron-donor
power of the supporting phosphine ligands enables a switch in selectivity
from demethylation of equatorial methyl ethers to 2° demethoxylation.
Applications of these accessible catalysts to the selective demethoxylation
of the 3α-methoxy group of cholic acid derivatives is demonstrated,
including a switch in observed selectivity controlled by 7α-substitution.
The resting state of the catalyst has been characterized for two phosphine
derivatives, demonstrating that the observed switch in C–O
cleavage selectivity likely results from electronic factors rather
than from a major perturbation of the catalyst structure.