One-step preparation of novel 1-( N -indolyl)-1,3-butadienes by base-catalysed isomerization of alkynes as an access to 5-( N -indolyl)-naphthoquinones

PIS DIEZ, C. M.; FERNANDEZ, J. F.; DI VENOSA, G.; CASAS, A.; PIS DIEZ, R.; PALERMO, J. A.

RSC Advances

Royal Society of Chemistry

Año: 2018 vol. 8 p. 35998 - 36006

A series of novel 1-(N-indolyl)-1,3-butadienes, as (1 : 1) mixtures of the (E) and (Z) dienes, was prepared in onestep by base-catalysed isomerization of N-alkylindoles with a terminal butyne chain. The reaction conditionsare mild, and in all cases the yields were very high (>90%). The (E) and (Z) dienes were separable by preparativeTLC and could be fully characterized. This isomerization proceeded readily in the case of a butynyl chain, butdidn´t take place with a pentynyl chain. A mechanism was proposed for this reaction, based on previous studieson the isomerization of alkynes in basic media, and a key intermediate that supports the proposed mechanismcould be isolated and fully characterized. A theoretical study of the proposed mechanism was performed bycomputational methods and the results validated the proposal. The reactivity of the synthesized dienes wasstudied in Diels?Alder reactions with p-benzoquinone, to obtain a small library of new 5-(N-indolyl)-1,4-naphthoquinones.The lack of reactivity in the case of the (Z) isomers was explained by calculation of therotational curves of the central bond of the (Z) and (E) dienes. Finally, the cytotoxicity of the new 5-(Nindolyl)-1,4-naphthoquinoneswas tested against a panel of three cell lines.