Toward understanding the regioselectivity of the one‐pot reaction of phenylene diamines with aldehydes and cyclopentadiene (Povarov reaction). Combined experimental and theoretical approaches

Three‐component acid‐catalyzed cyclocondensation of isomeric phenylenediamines with aldehydes and cyclopentadiene (CPD) was studied. In the M06‐2X//B3LYP/6–311 + G(d,p) + IEFPCM(SMD) approximation, a quantum chemical model was developed, energies of the PES stationary points were determined, and activation barriers were found for the CPD addition to the protonated Schiff base (rate‐limiting step) and for electrophilic carbocation cyclization to give endo, endo (syn)‐ or endo, exo (anti)‐cyclopentene‐annulated octahydropyridoquinoline‐ and octahydrophenanthroline‐based cycloadducts. The calculation results are in full agreement with the experimental data, which indicate that the cyclocondensation involving p‐phenylenediamine affords both types of cycloadducts, whereas the reactions of o‐ or m‐phenylenediamine lead to regioselective formation of octahydro‐1,10‐phenanthroline‐ or octahydropyridoquinoline‐based product, respectively. According to homo‐ and heteronuclear correlation 1Н and 13С NMR experiments and X‐ray diffraction data, the newly formed asymmetric centers of the cyclopentene‐annulated tetrahydroquinoline moiety in the polycyclic products have exo (endo)‐cis‐orientation. According in silico calculation results and the obtained experimental data, the trifluoroacetic acid‐catalyzed reaction of (o‐, m, p‐) phenylenediamine, aldehyde, and CPD affords regioisomeric octahydropyridoquinolines and/or octahydrophenanthrolines with syn‐ and anti‐oriented cyclopentene moiety.