Binaphthalene-based cyclic homochiral ureas and their structure-related properties

Abstract

Enantiomeric purity control is a must when working with chiral drugs. In this context, homochiral cycles consisting solely of 1 to 3 binaphthalene units interconnected with urea moieties were tested as chiral solvating agents for enantiomers of naproxen. Among the tested compounds, only the dimeric structure formed stable diastereomeric complexes with naproxen with K_R = 43 ± 3 M⁻¹/K_S = 34 ± 2 M⁻¹. When the conformational mobility of the dimer was decelerated by cooling to −30 °C, the complexes became stronger (K_R-30 = 100 ± 6 M⁻¹/K_S-30 = 102 ± 7 M⁻¹). Using DFT calculations, the probable structures of the diastereomeric complex were proposed.