Synthesis and Stereodynamics of Highly Constrained 1,8-Bis(2,2‘-dialkyl-4,4‘-diquinolyl)naphthalenes (2)

Axially chiral 1,8-bis(2,2‘-diphenyl-4,4‘-diquinolyl)naphthalene, 8, and 1,8-bis(2,2‘-diisopropyl-4,4‘diquinolyl)naphthalene N,N‘-dioxide, 9, have been prepared to study the stereodynamics of these
and other 1,8-diheteroarylnaphthalenes based on reversible first-order isomerization kinetics and
crystallographic data. The ratio of the two enantiomeric anti-conformers to the meso syn-isomer of
8 and 9 was determined as 1.2:1 and 9.6:1. Investigation of the conformational stability of the
atropisomers at enhanced temperatures using HPLC and NMR spectroscopy revealed a Gibbs
activation energy of 122.4 (121.8) kJ/mol and 115.2 (109.0) kJ/mol for the anti/syn- (syn/anti)-isomerization of 8 and 9, respectively. Comparison of the conformational stability of a series of
1,8-dipyridylnaphthalenes and 1,8-diquinolylnaphthalenes shows that the latter exhibit a significantly higher rotational energy barrier. While the syn- and anti-isomers of 1,8-dipyridylnaphthalenes
interconvert rapidly at room temperature the stereoisomers of 1,8-diquinolylnaphthalenes can be
isolated by chromatography or crystallization and stored at 25 °C for several months without any
sign of racemization. The conformational stability of 1,8-diquinolylnaphthalenes is a consequence
of significantly increased steric hindrance to isomerization in a highly congested T-shaped transition
state. Conversion of 1,8-diheteroarylnaphthalenes to their corresponding N,N‘-dioxides was found
to result in an increased anti/syn-ratio and decreased rotational energy barrier, which was
attributed to synergistic repulsive dipole/dipole interactions destabilizing the diastereomeric ground
states and facilitated out-of-plane bending reducing the steric hindrance in the T-shaped transition
state.