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

Abstract

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 degrees 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.

Ab initio study of atropisomers of derivatives of 1,8-di-pyridine 9H-fluorene, dibenzo[b,d]furan, 9H-carbazole and dibenzo[b,d]thiophene

“…Thus separation of these isomers is not expected to be feasible. These findings are in agreement with previous reports [13][14][15].…”

“…Very few p-stacked molecules that can be used as experimental models for these interactions have been synthesized to date [1,7,[12][13][14].…”

“…The synthesis of conformationally stable atropisomers of 1,8-diaryl or heteroaryl naphthalenes is recently reported [1,[8][9][10][11][12][13][14]. These compounds show anti-syn atropisomerism at ambient temperature.…”

Novel foldamer structural architecture from cofacial aromatic building blocks

“…1(a) and ( b)) facilitates the molecule to grow further co-facially, as evident from the solid-state structure, although the pyridyl rings at the termini are splayed out presumably to minimize steric interactions and throughspace Coulomb repulsion. 19 Interestingly, 3 undergoes hydrogen bond-mediated duplex formation through intermolecular interactions (Fig. 1(c) and (d)).…”

Functional diversity in templated solid state reactions

“…In this chapter, the use of a template to direct an intramolecular 85b). [124][125][126] To our knowledge, our work provides the first example of an intramolecular…”