Fluorous phase-based fluorescent sensing

Fluorous phase-based fluorescent sensing has been developed for selective recognition of chiral amino alcohols, diamines and amino acids, as well as for the rapid analysis of asymmetric reactions. The optically active probe (R)- or (S)-1 containing a chiral BINOL unit with two perfluoroalkyl-substituted ketones was used for the enantioselective fluorescent recognition of chiral amino alcohols and diamines in fluorous solvents. In several systems, one substrate enantiomer induced over 1000 folds of fluorescence enhancements, while the opposite enantiomer produced much weaker responses. Mechanistic investigations revealed that the fluorous phase promoted selective adduct formation and aggregation processes that rigidified molecular structures and generated greatly enhanced emission. These large fluorescence differences allowed direct determination of enantiomeric composition and, in some cases, visual discrimination of enantiomers under ultraviolet illumination. The highly fluorinated aldehyde (S)-11 was found to show enantioselective fluorescent recognition of chiral diamines in biphasic system. The racemic 1 could also be employed for enantiomeric composition analysis. Its fluorescence response was found to be strongly dependent on substrate enantiomeric excess but not on substrate concentration. A bisBINOL-based fluorescent probe capable of forming Zn(II)-assisted complexes exhibited highly enantioselective responses toward numerous amino acids. Incorporation of fluorinated chains enabled the resulting probe (R,R)-16 to operate in fluorous biphasic media, where amino acids could be extracted from aqueous solution into the fluorous phase for analysis. This probe provided sensitive determination of amino acid enantiomeric composition. The fluorous phase-based probes (S,S)-17, (R)-21 and 24 were found to show highly selective fluorescent responses toward specific amino acids. Across these systems, the fluorous medium played an active role by promoting molecular rigidification and suppressing nonradiative relaxation pathways. Applications of the fluorescent probes in the screening of asymmetric reactions have been demonstrated. Fluorescence measurements performed in a separate fluorous phase allowed rapid determination of product enantiomeric composition from crude reaction mixtures while minimizing interference from substrates, catalysts, and byproducts. A catalytic asymmetric ring-opening reaction of epoxides and an enzymatic hydrolysis of amino acid esters were investigated. The fluorescence-derived results correlated well with conventional chiral HPLC analyses while enabling much faster evaluation of reaction conditions and catalyst performance.