Water-Soluble Calix[4]resorcarenes as Enantioselective NMR Shift Reagents for Aromatic Compounds

Abstract

A tetra L-prolinylmethyl derivative of a tetra-sulfonated calix[4]resorcarene (1) is an effective chiral NMR solvating agent for water-soluble compounds with phenyl, pyridyl, bicyclic aromatic, or indole rings. These aromatic compounds form host-guest complexes with the calix[4]resorcarene in water. Complexation of substrates with the calix[4]resorcarene is likely promoted by hydrophobic effects, and bicyclic substrates have association constants with the calix[4]resorcarene larger than those of similar phenyl-containing compounds. Aromatic resonances of the substrates show substantial upfield shifts because of shielding from the aromatic rings of the calix[4]resorcarene, and several resonances in the 1H NMR spectra typically exhibit enantiomeric discrimination. The extent of enantiomeric discrimination depends in part on interactions of the substituent groups of the substrates with the prolinylmethyl groups of the calix[4]resorcarene. The effectiveness of a calix[4]resorcarene prepared from N-methyl-L-alanine (2) as a chiral NMR discriminating agent is compared to the L-prolinylmethyl derivative.

Water‐soluble calix[4]resorcinarenes as chiral NMR solvating agents for bicyclic aromatic compounds

“…[53][54][55] The stronger association is most likely because of the relative hydrophobicities of phenyl and bicyclic rings. Bicyclic rings, being more hydrophobic than phenyl rings, will have a greater energetic stabilization when involved in host-guest complexes with the calixresorcinarenes in water.…”

Water‐Soluble Calix[4]resorcinarenes with Hydroxyproline Groups as Chiral NMR Solvating Agents for Phenyl‐ and Pyridyl‐Containing Compounds

“…Prior studies of 22-24 with SCRPro indicated that the phenyl ring was inhibited from associating with the cavity because of the halide atom. [27] Association of 22-24 involved insertion of the pyridyl ring into the cavity in such a manner that the changes in chemical shifts for H4Ј and H5Ј were greater than those of H3Ј and H6Ј. Compounds 21 and 22 were shown to associate with SCR-Pro through insertion of both the phenyl and pyridyl ring, although binding through the pyridyl ring was more favorable.…”

“…[29] Compounds 20-24 have a pyridyl ring that is also capable of association within the cavity of the calix [4]resorcinarenes. [27] The shielding of the aromatic hydrogen atoms of every substrate with a monosubstituted phenyl ring (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) in the presence of each calix [4]resorcinarene vary in the order Hp Ͼ Hm Ͼ Ho, where these refer to the positions relative to the substituted carbon atom of the ring. The especially large shielding of the hydrogen atoms of the aromatic rings combined with the order of perturbations of chemical shifts indicates that the association geometry involves insertion of the aromatic ring into the cavity with the Hp position being deepest.…”

“…[25][26][27] SCR-Pro exists in aqueous solution in a cone-shaped configuration with a well-defined cavity. Water-soluble organic salts with mono-or ortho-substituted phenyl rings and mono-or 2,3-disubstituted naphthyl rings form host-guest complexes by insertion of the aromatic ring into the cavity of SCR-Pro.…”

NMR enantiodifferentiation of quaternary ammonium salts of Tröger base

“…[32][33][34] Although efficient NMR enantiodifferentiation is regularly achieved among ions in ''low polarity'' halogenated solvents, it is not the case in high polarity solvents as a result of weaker electrostatic interactions. 35,36 Cations and anions, and small organic ones in particular, tend to behave as dissociated ion pairs in such solvents and hence a sharp decrease in NMR enantiodifferentiation. 37 It was thus debatable whether an effective NMR discrimination of quaternary ammonium organic cations could be achieved in polar solvent medium.…”