New nucleophilic rearrangement in the mechanism of the three-component domino cyclisation affording fluoroalkylated (pyrrolo)quinazolines

•Mechanism of the domino three-component cyclisation was studied, which consists of three or four steps depending on the character of highly reactive component.•A new nucleophilic rearrangement was proved as the crutial step of the cyclisation.•The cyclisation was extended to highly reactive ketones, e.g. hexafluoroacetone.

The following mechanism steps were verified for the three-component domino cyclisation affording (pyrrolo)quinazolines from 2-(aminomethyl)aniline, a very reactive oxo compound and “usual” oxo compound. The first step was a rapid reaction of very reactive oxo compound (trifluoropyruvate or hexafluoroacetone) with benzylic amino group to form hemiaminal, but not imine; the second step was the reaction of oxo compound with aromatic amino group to form imine (Schiff base) being in equilibrium with its enamine form; the third step was an intramolecular attack of the hemiaminal carbon by the enamine carbon followed by a new nucleophilic rearrangement to form tetrahydropyrimidine cycle; the forth step was closure of the lactam ring, if ester group was available as in trifluoropyruvate.

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