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

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

RSC Advances

The Royal Society of Chemistry

Año: 2018

2046-2069

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 conditionsaremild, 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 placewith a pentynyl chain. Amechanismwas proposed for this reaction, based on previous studieson the isomerization of alkynes in basicmedia, and a key intermediate that supports the proposedmechanismcould 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-naphthoquinones was tested against a panel of three cell lines.