Hydrogen-bonding sheets in crystals for chirality recognition: synthesis and application of (2 S,3 S) -2,3-dihydroxy- and (2 S,3 S) -2,3-dibenzyloxy-1,4-bis(hydroxyamino)butanes

Abstract

Two enantiopure bis(hydroxyamino) compounds were successfully prepared from dialkyl tartrate by a chiral-pool method and applied as basic resolving agents in the enantioseparation of 2-arylpropanoic acids and arylglycolic acids. (2 S,3 S) -2,3-Dihydroxy-1,4-bis(hydroxyamino)butane (2 S,3 S) - 1a could moderately recognize the chirality of the 2-arylpropanoic acids, while (2 S,3 S) -2,3-dibenzyloxy-1,4-bis(hydroxyamino)butane (2 S,3 S) - 1b could not due to the low crystallinity of both the corresponding diastereomeric salts. On the other hand, (2 S,3 S) - 1b showed a similar chirality-recognition ability for the arylglycolic acids. The ability of (2 S,3 S) - 1b was different from those generally observed for widely used primary amine-type resolving agents with regard to the relationship between the resolution efficiency and the similarity in the relative molecular length of a resolving agent and a target racemate. The X-ray crystallographic analyses of the less-soluble diastereomeric salts revealed that in the salts (2 S,3 S) - 1a formed a supramolecular sheet, of which the distance was variable to make the resultant dissymmetric space fit to the shape of the target acids, and that (2 S,3 S) - 1b was constructed from a robust supramolecular sheet, consisting of hydrogen-bonding 2 1 columns, with the participation of the hydroxy group of the arylglycolic acids. These X-ray crystallographic analyses also suggested that for the formation of a supramolecular sheet, the coexistence of two hydroxyamino groups is essential.