Probing the discriminating power of chiral crown hosts by CD spectroscopy

The discriminating efficiency of pyridino- (1), pyridono- and thiopyridono- (2), phenazino- (3), and acridino- (4) 18-crown-6 hosts as well as pyridino- (1) and phenazino- (3) 18-crown-6 hosts with allylic moieties attached either to the macrocyclic ring [X=CH-CH(2)-CH=CH(2) or C(CH(2)-CH=CH(2))(2)] or to the heterocyclic subunit was probed by circular dichroism (CD) spectroscopy using enantiomers of alpha-(1-naphthyl)- ethylamine hydrogen perchlorate (1-NEA). The CD spectra of the diastereomeric complexes as well as the difference and sum of the spectra were analyzed. Titration experiments were also performed monitored by CD or UV spectroscopy. The CD- and (1)H NMR-based enantiomeric preferences were compared. CD spectroscopy showed that the relative stability of heterochiral [(R,R)-host/(S)-guest or (S,S)-host/(R)-guest] complexes generally exceeds that of homochiral [(R,R)/(R)-or (S,S)/(S)] complexes. Bulkier substituents (R=iBu, sBu or tBu) decrease complex stability but increase the discriminating power of the host. According to (1)H NMR titration, attachment of one allylic linker group in position X of the macro ring [(S,S)-1b, (S,S)-1e] changes the discriminating preference (from heterochiral to homochiral) of the parent hosts (S,S)-1a and (S,S)-1d. This change of discriminating preference was not reflected in the CD spectra. Host (S,S)-1g with an allyloxy linker group in position gamma of the pyridine ring gives CD spectra which clearly reflect the high discriminating power and enantiomeric preference of the host. The exciton-coupled circular dichroism (ECCD) spectra of the 1-NEA complexes of phenazino and acridino hosts allow reliable determination of the enantiomeric preference by comparing the A values of the exciton couplets. An allylic group appended to the macrocyclic ring or the N-containing heterocyclic subunit allows for the attachment of the chiral discriminator to the solid matrix of a chromatographic sorbent and also serves as a spectroscopic label of the host. CD spectroscopy is a simple and rapid method, providing qualitative information on enantiomeric discrimination. It can be of great help in designing and testing new host molecules.