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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