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

Man, X.; Jiang, Y.-Y.; Liu, Y.; Bi, S.* Organometallics 2017, 36, 2843–2852. Download Link

Abstract: 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 fivemembered-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 ratedetermining 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.