Comprehensive Chirality Sensing: Development of Stereodynamic Probes with a Dual (Chir)optical Response

The
attachment of a salicylaldehyde ring and a cofacial aryl or
heteroaryl N-oxide chromophore onto a naphthalene
scaffold affords stereodynamic probes designed to rapidly bind amines,
amino alcohols, or amino acids and to translate this binding event
via substrate-to-receptor chirality amplification into a dual (chir)­optical
response. 1-(3′-Formyl-4′-hydroxyphenyl)-8-(9′-anthryl)­naphthalene
(1) was prepared via two consecutive Suzuki cross-coupling
reactions, and the three-dimensional structure and racemization kinetics
were studied by crystallography and dynamic HPLC. This probe proved
successful for chirality sensing of several compounds, but in situ
IR monitoring of the condensation reaction between the salicylaldehyde
moiety in 1 and phenylglycinol showed that the imine
formation takes 2 h. Optimization of the substrate binding rate and
the circular dichroism (CD) and fluorescence readouts led to the replacement
of anthracene with smaller fluorophores capable of intramolecular
hydrogen bonding. 1-(3′-Formyl-4′-methoxyphenyl)-8-(4′-isoquinolyl)­naphthalene N-oxide (2) and its pyridyl analogue 3 combine fast substrate binding with distinctive chiral amplification.
This asymmetric transformation of the first kind prompts CD and fluorescence
responses that can be used for in situ determination of the absolute
configuration, ee, and total concentration of many compounds. The
general utility of the three chemosensors was successfully tested
on 18 substrates.