Facial control of gas-phase enantioselectivity of strapped tetra-amide macrocycles

Abstract

The reactivity of proton-bound diastereomeric [M·H·A]⁺ complexes (A = amino acid; M = “strapped” tetra-amide macrocycle) towards the 2-aminobutane enantiomers (B) has been investigated in the gas phase by ESI-FT-ICR mass spectrometry. The displacement of the A guest from the diastereomeric [M·H·A]⁺ complexes by reaction with B exhibits a distinct enantioselectivity which markedly depend upon the presence of a π ring in A and on the nature of the intramolecular chain in the strapped macrocycle, whether –(CH₂)₁₀– (II) or –(C₂H₄O)₅– (III). The emerging picture confirms the view that the chiral tetra-amide macrocycle II, characterized by an intramolecular decamethylene chain, may acquire in the gas phase a different conformation by induced fit on complexation of the selected A guests on the convex face of the host. This leads to the coexistence in the gas phase of stable diastereomeric [M·H·A]⁺ eq–eq and ax–ax structures, in proportions depending on the configuration of A and M and characterized by different stability and reactivity towards the 2-aminobutane enantiomers. When the decamethylene chain of the host is replaced by the –(CH₂CH₂O)₅– chain, as in III, the guest A is blocked on the concave face of the host by complexation of its ammonium group by the “crown-ether”-like chain of the host and, therefore, the B-to-A displacement exhibits a more pronounced enantioselectivity.