Induced Circular Dichroism of Achiral Cyclic Bisurea via Hydrogen Bonds with Chiral Carboxylates.

Abstract

Chiral induction properties of achiral bisurea derivatives by binding tetrabutylammonium salts of N-acetylated chiral carboxylates (Ac-AlaO-, Ac-ValO-, Ac-LeuO-, and Ac-PheO-) was studied. Ultraviolet-visible titrations showed 1:1 complex formation between the bisureas and the carboxylates. The calculated association constants of cyclic bisurea (1a) were 5-10 times larger than those of the acyclic derivative (2), and 1a showed the highest binding affinity for Ac-LeuO-. While circular dichroism (CD) of both 1a and 2 was induced upon the addition of chiral carboxylates, the CD intensity of 1a was greater than that of 2. Especially, the intensity induced by chiral Ac-LeuO- was the greatest. 1H nuclear magnetic resonance titrations and density functional theory (DFT) calculations showed the cooperative hydrogen bonds of four urea N-Hs and the carboxylate group and the CH-π interactions between a naphthyl unit of 1a and the methyl moieties of Ac-LeuO-. Furthermore, DFT calculations suggested that the twisted anticlockwise conformation of 1a would be dominantly induced by Ac-d-LeuO-. The CD intensity changes of 1a showed a good linear relationship with the enantiomeric excess (ee) values of Ac-LeuO-; therefore, 1a could be utilized as a stereodynamic chiral probe for determining the ee of chiral anions.