Unprotected Galactosamine as a Dynamic Key for a Cyclochiral Lock

The discrimination of d-galactosamine (<b>G</b>), representative of the amino-sugar class of compounds, has been probed through nano-ESI-FT-ICR mass spectrometry by isolating the relevant [<b>C</b>·H·<b>G</b>]⁺ proton-bound complexes with the enantiomers of the cyclochiral resorcin[4]­arene <b>C</b> and allowing them to react toward three primary amines (<b>B</b> = EtNH₂, <i>i</i>PrNH₂, and (<i>R</i>)- and (<i>S</i>)-<i>s</i>BuNH₂). The system under investigation presents several features that help to unveil the behavior of unprotected <b>G</b> in such a supramolecular architecture: (i) the hydrophobic derivatization of the <b>C</b> convex side forces the polar guest <b>G</b> to be coordinated by the cyclochiral concave region; (ii) protonated d-galactosamine exists as an anomeric mixture, dynamically interconverting throughout the experimental time-window; and (iii) different basicities of <b>B</b> allow the experiment to subtly tune the reactivity of the [<b>C</b>·H·<b>G</b>]⁺ complexes. Three [<b>C</b>·H·<b>G</b>]⁺ aggregate-types were found to exist, differing in both their origin and reactivity. The most reactive adducts ([<b>C</b>·H·<b>G</b>]_ESI⁺), generated in the electrospray environment, undergo a <b>G</b>-to-<b>B</b> ligand exchange in competition with a partial isomerization to the unreactive [<b>C</b>·H·<b>G</b>]_GAS⁺-type complexes. Finally, the poorly reactive [<b>C</b>·H·<b>G</b>]_SOL⁺ aggregates are formed in solution over an hours-long time scale. A cyclochirality effect on the reactivity was found to depend on the considered [<b>C</b>·H·<b>G</b>]⁺ aggregate-type.