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.