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

The reactivity of proton-bound diastereomeric [M center dot H center dot 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 center dot H center dot A](+) complexes by reaction with B exhibits a distinct enantioselectivity which markedly depend upon the presence of a pi ring in A and on the nature of the intramolecular chain in the strapped macrocycle,whether -(CH(2))(10)- (II) or -(C(2)H(4)O)(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 center dot H center dot 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 -(CH(2)CH(2)O)(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