peri -Interactions in 1,8-bis(dimethylamino)naphthalene ortho -ketimine cations facilitate [1,5]-hydride shift: selective synthesis of 1,2,3,4-tetrahydrobenzo[ h ]quinazolines.

Selective heterocyclization leading to 1,2,3,4-tetrahydrobenzo[ h ]quinazolines from ortho -ketimines of 1,8-bis(dimethylamino)naphthalene ( DmanIms ) under acid catalysis has been revealed. In contrast to the rather unreactive N , N -dimethylaniline ortho -ketimine, DmanIms readily undergo this transformation without an additional catalyst. This distinction in the reactivity underscores the importance of the second peri -NMe 2 group in DmanIms , which facilitates a [1,5]-hydride shift and the subsequent cyclization. The cascade of peri -interactions emerging between 1-NMe 2 and 8-NMe 2 groups has been identified as a reason for the catalytic effect: (1) the hydrogen bond in the DmanIm dication constrains 1-NMe 2 in the desired position providing proximity of reaction centers, (2) the repulsion of the lone pairs of 8-NMe 2 group and unrelaxed 1-NMe 2 group arising right after deprotonation process reduces the Gibbs free energy of activation (ΔG ‡ ) for the straight hydride shift, and (3) the electrostatic interaction between 8-NMe 2 and the charged NCH 2 + group in the intermediate increases the Δ G ‡ for the reverse hydride shift.