Mechanistic Study on Platinum-Catalyzed Domino Reaction of Benziodoxole and Pyrrole Homopropargylic Ethers for Indole Synthesis

Benzene
ring functionalization provides useful alternatives to access indole
derivatives and has received much attention in recent years. In this
work, the mechanism of Pt­(II)-catalyzed cyclization/alkynylation of
benziodoxole with pyrrole homopropargylic ethers to generate C5-alkenylated
indole derivatives has been studied with the aid of density functional
theory (DFT) calculations. We found that five-membered-ring cyclization/six-membered-ring
cyclization is competitive in the formation of an indole skeleton.
The following aromatization stage prefers the reaction sequence bicarbonate-assisted
deprotonation at the C3a position, H2CO3-promoted
methoxy elimination at the C7 position, and bicarbonate-assisted deprotonation
at the C6 position. In the last alkynylation stage, the oxidative
substitution mechanism assisted by H2CO3 is
found to be favored over the previously proposed 1,2-iodo shift and
oxidative addition. The overall rate-determining step is oxidative
substitution. Additionally, an interesting substituent effect on chemoselectivity
was investigated. The electronic and steric effects caused by methyl
result in reverse chemoselectivity.