Hydroamination of 2-Ethynyl-4,5,6,7-tetrahydroindoles: Toward 2-Substituted Amino Derivatives of Indole

Hydroamination of 1-phenyl-3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-yn-1-ones with secondary dialkylamines proceeds under mild conditions (room temperature, aqueous ethanol, 1 h) to afford the corresponding (2E)-3-dialkylamino-3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-en-1-ones in 72-92% stereoselectivity and 64-88% yield. Under the same conditions, ethyl 3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-ynoates react with dimethylamine and diethylamine in different ways; dimethylamine converts the ester function into an amide, giving the corresponding N,N-dimethyl-3-(4,5,6,7-tetrahydro-1H-indol-2-yl)prop-2-ynamides in 70-86% yield, whereas diethylamine adds to the triple bond to give the corresponding ethyl 3-(diethylamino)-3-(4,5,6,7-tetrahydro-1H indol-2-yl)prop-2-enoates with ∼100% stereoselectivity and up to 85% yield. The difference in the reactivity of the two amines can be rationalized in terms of steric hindrance.