TY - JOUR

T1 - 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

AU - Mikshiev, Vladimir Y.

AU - Tolstoy, Peter M.

AU - Puzyk, Aleksandra M.

AU - Kirichenko, Sergey O.

AU - Antonov, Alexander S.

PY - 2022

Y1 - 2022

N2 - 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-NMe2 group in DmanIms, which facilitates a [1,5]-hydride shift and the subsequent cyclization. The cascade of peri-interactions emerging between 1-NMe2 and 8-NMe2 groups has been identified as a reason for the catalytic effect: (1) the hydrogen bond in the DmanIm dication constrains 1-NMe2 in the desired position providing proximity of reaction centers, (2) the repulsion of the lone pairs of 8-NMe2 group and unrelaxed 1-NMe2 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-NMe2 and the charged N[double bond, length as m-dash]CH2+ group in the intermediate increases the ΔG‡ for the reverse hydride shift.

AB - 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-NMe2 group in DmanIms, which facilitates a [1,5]-hydride shift and the subsequent cyclization. The cascade of peri-interactions emerging between 1-NMe2 and 8-NMe2 groups has been identified as a reason for the catalytic effect: (1) the hydrogen bond in the DmanIm dication constrains 1-NMe2 in the desired position providing proximity of reaction centers, (2) the repulsion of the lone pairs of 8-NMe2 group and unrelaxed 1-NMe2 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-NMe2 and the charged N[double bond, length as m-dash]CH2+ group in the intermediate increases the ΔG‡ for the reverse hydride shift.

UR - https://pubs.rsc.org/en/content/articlelanding/2022/OB/D2OB00674J

U2 - 10.1039/D2OB00674J

DO - 10.1039/D2OB00674J

M3 - Article

VL - 20

SP - 4559

EP - 4568

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

ER -