Transition‐Metal‐Catalyzed Regioselective Alkylation of Indoles with Alcohols

The regioselective alkylation of indoles with alcohols as alkylating reagents was developed by using Pd/C or RuCl2(PPh3)(3)/DPEphos {DPEphos = bis[(2-diphenylphosphanyl)phenyl] ether}as catalysts. The reaction of indole with benzyl alcohol in the presence of Pd/C and K2CO3 at 80 degrees C for 24 h without any solvent under in air yielded 90% of 3-benzylindole. The corresponding 3-benzylindole was obtained in 99% yield when the reaction was catalyzed by RuCl2(PPh3)(3)/DPEphos in the presence of K3PO4 at 165 degrees C for 24 h under argon. Several types of alcohols were treated with indoles under these conditions to give the corresponding 3-alkylated indoles in high yields (up to 99%). This reaction may involve the catalyst-mediated transformation of alcohols to aldehydes, nucleophilic addition of indole to the resulting aldehydes accompanied by dehydration, and then hydrogenation.