Breaking the C₃-Symmetry of Chiral Tripodal Oxazolines:  Enantio-Discrimination of Chiral Organoammonium Ions

Abstract

[structure: see text] A phenylglycinol-derived tripodal oxazoline with C1-symmetry (C1-PhBTO) was synthesized, and its enantioselective recognition behavior toward alpha-chiral primary organoammonium ions was studied. The C1-PhBTO receptor showed higher selectivity with an opposite sense of enantio-discrimination compared to other C1-symmetric analogues examined but lower selectivity with the same sense of enantioselection compared to its C3-symmetric analogue. Binding studies indicated that the C1-symmetric receptors, particularly C1-PhBTO, interact with the guests in a 2:1 host-guest complex mode in stark contrast to its C3-symmetric analogues.

Molecular recognition of organic ammonium ions in solution using synthetic receptors

“…Theoretical studies indicated such trisoxazolines are alternatives to azacrowns for binding and sensing of ammonium and alkylammonium ions [565–567]. The importance of the C 3 symmetry in chiral recognition has been pointed out [555].…”

Can C3‐Symmetric Receptors Differentiate Enantiomers?

“…It may certainly be the case that the energy difference between the host–guest complexes of enantiomeric ammonium ions with a host with lower symmetry ( C 1 or C 2 ) is larger, but there is no fundamental rule governing these differences. To further study the role of symmetry, Ahn and co‐workers recently prepared a receptor, 4 , with reduced symmetry in which one of the substituents was replaced by one with opposite chirality 8. This led to lower selectivity but also to a different type of binding (2:1 host–guest complex) owing to the different structures of the ligands.…”

Chiral Heterocycle-Based Receptors for Enantioselective Recognition

“…Removing the β-OH group from 225, as in 226 or 227, (Figure 22) results in low enantioselectivities, hence indicating that the secondary H-bond interaction is critical to secure the necessary environment for chiral discrimination as confirmed by the crystallographic structure of the corresponding 215-225 complex. In the next article [93] the development of a benzene-based tripodal oxazoline receptor with C1-symmetry, 234 upon changing the symmetry of chiral environment from C3 to C1 was reported (Scheme 38). The synthetic strategy was based on the coupling of tris-(cyanomethyl)mesitylene with (S)-phenylglycinol in the presence of 5 mol % Cd(OAc)2 to furnish (S,S)-bis(oxazoline), 233 and subsequent treatment with (R)-phenylglycinol under the similar reaction conditions afforded (S,S,R)-234 in 28% isolated yield.…”

“…In the next article [93] the development of a benzene-based tripodal oxazoline receptor with C1-symmetry, 234 upon changing the symmetry of chiral environment from C3 to C1 was reported (Scheme 38). The synthetic strategy was based on the coupling of tris-(cyanomethyl)mesitylene with (S)-phenylglycinol in the presence of 5 mol % Cd(OAc)2 to furnish (S,S)-bis(oxazoline), 233 and subsequent treatment with (R)-phenylglycinol under the similar reaction conditions afforded (S,S,R)-234 in 28% isolated yield.…”