It was recently shown that 7-azaindole, when subject to indoxyl-generating conditions, produces 7,7-diazaindirubin selectively over 7,7-diazaindigo. It was proposed that this reaction proceeds through a condensation pathway between the keto and enol tautomeric forms of 7-azaindoxyl, followed by oxidation to indirubin. Subsequent work related to further elucidation of the mechanistic pathway and progress towards the development of a broader synthetic methodology will be discussed. It was observed that lower temperatures are paramount to enhancing the selectivity for these processes for indirubin over indigo. A broad range of substrates are currently being explored to help determine the scope and limitation of this process. Mechanistically, indigo synthesis is likely inhibited due one or both of the following hypotheses: energetic needs for indole dimerization are not being met at lower temperatures and/or concentrations of available free-radical, implicated as an intermediate, place kinetic limitations on the reaction. A complementary method using a rare earth triflate Lewis acid to promote indirubin synthesis will also be discussed.

The direct synthesis of indirubins from indoles through an indoxyl intermediate

ACS Spring Meeting 2021

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