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

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. (2S,3S)-2,3-Dihydroxy-1,4-bis(hydroxyamino)butane (2S,3S)-1a could moderately recognize the chirality of the 2-arylpropanoic acids, while (2S,3S)-2,3-dibenzyloxy-1,4-bis(hydroxyamino)butane (2S,3S)-1b could not due to the low crystallinity of both the corresponding diastereomeric salts. On the other hand, (2S,3S)-1b showed a similar chirality-recognition ability for the arylglycolic acids. The ability of (2S,3S)-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 (2S,3S)-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 (2S,3S)-1b was constructed from a robust supramolecular sheet, consisting of hydrogen-bonding 21 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.

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(2S,3S)-2,3-Dihydroxy-1,4-bis(hydroxyamino)butaneC4H12N2O4[α]D = +54.3 (c 1.44, H2O)Configuration: (R,R)-tartaric acid

(2S,3S)-2,3-Benzyloxy-1,4-bis(hydroxyamino)butaneC18H24N2O4[α]D = −36.0 (c 1.03, MeOH)Configuration: (R,R)-tartaric acid