Platinum-catalyzed multistep reactions of indoles with alkynyl alcohols

PtCl2 effectively catalyzes the multistep reaction of N-methyl indole (1 a) with pent-3-yn-1-ol (2 a) in THF at room temperature for 2 h to give indole derivative 3 a, which contains a five-membered cyclic ether group at C3 in 93% yield. Under similar reaction conditions, various substituted N-methyl indoles 1 b-h and indole (1 i) reacted efficiently with 2 a to afford the corresponding indole derivatives 3 b-h and 3 i in 48-91 and 72% yields. The results showed that N-methyl indoles with electron-donating substituents were more reactive affording higher product yields than those with electron-withdrawing groups. Likewise, various substituted but-3-yn-1-ols 2 b-e and other longer chain alkynyl alcohols 2 f-i also underwent a cyclization-addition reaction with N-methyl indole (1 a) to provide the corresponding cyclization-addition products 3 j-m and 3 a, 3 j, and 3 n-o in good to excellent yields. The present platinum-catalyzed cyclization-addition reaction can be further extended into N-methyl pyrrole. Mechanistically, the catalytic reaction proceeds by an intramolecular hydroalkoxylation of alkynyl alcohol to afford cyclic enol ether followed by the addition of the C--H bond of indole to the unsaturated moiety of cyclic enol ether providing the final product. Experimental evidence to support this proposed mechanism is provided.