Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures

Abstract

Click reactions have become powerful synthetic tools with unique applications in the health and materials sciences. Despite the progress with optical sensors that exploit the principles of dynamic covalent chemistry, metal coordination or supramolecular assemblies, quantitative analysis of complex mixtures remains challenging. Herein, we report the use of a readily available coumarin conjugate acceptor for chiroptical click chirality sensing of the absolute configuration, concentration and enantiomeric excess of several compound classes. This method has several attractive features, including wide scope, fast substrate fixation without by-product formation or complicate equilibria often encountered in reversible substrate binding, excellent solvent compatibility, and tolerance of air and water. The ruggedness and practicality of this approach are demonstrated by comprehensive analysis of nonracemic monoamine samples and crude asymmetric imine hydrogenation mixtures without work-up. Click chemosensing addresses increasingly important time efficiency, cost, labor and chemical sustainability aspects and streamlines asymmetric reaction development at the mg scale.

Chemoselective bioconjugation based on modular click chemistry with 4-halocoumarins and aryl sulfonates

“…Our laboratory has recently introduced small molecular optical probes that achieve click chemistry sensing of the enantiomeric composition and concentration of free amino acids in aqueous solutions. [33][34][35][36] The term 'click chemistry' generally refers to a small set of privileged reactions that proceed smoothly with high yields and minimal byproduct formation under mild conditions in environmentally benign solvents. Additional characteristics include operationally simple reaction protocols, the exclusive use of nonhazardous materials and the elimination of cumbersome chromatographic work-up steps, which altogether minimize necessary safety precautions, waste production and cost.…”

Stereochemical analysis of chiral amines, diamines, and amino alcohols: Practical chiroptical sensing based on dynamic covalent chemistry

“…bond formation with a chiral analyte to generate a CD signal that can be used for absolute configuration and ee determination have been developed by several groups. [44][45][46][47][48][49][50][51][52] Nevertheless, reversible Schiff base formation with chiral amines has become a very popular and highly successful CD sensing strategy. 27,28,30,39,41,53,54 We now wish to report a highly practical method that allows chiroptical ee analysis of a wide range of amines and amino alcohols using an inexpensive commercially available benzaldehyde derivative as probe.…”

“…The large majority of CD sensing assays introduced so far relies on the formation of supramolecular assemblies, metal coordination complexes, hydrogen bond adducts, or dynamic covalent chemistry (DCC) . In addition, stereodynamic probes that undergo irreversible covalent bond formation with a chiral analyte to generate a CD signal that can be used for absolute configuration and ee determination have been developed by several groups . Nevertheless, reversible Schiff base formation with chiral amines has become a very popular and highly successful CD sensing strategy .…”

Chiral Induction and Remote Chiral Communication in Quinoline Oligoamide Foldamers for Determination of Enantiomeric Excess and Absolute Configuration of Chiral Amines and Their Derivatives

“…Axially chiral compounds, such as biaryl compounds have been widely exploitedf or chiral molecular sensing because of their unique structures and stereodynamic properties. Wolf,[5] Pu [6] ando thers [3b, 7] have developed af ew elegant examples of axiallyc hiral probesf or the determination of absolutec onfiguration and enantiomeric excesso fs mall chiral organic molecules.M ost of the probes operate through mechanisms based on dynamic covalentc hemistry,m etal complex coordination, and supramolecular chemistry,w hich generate characteristic optical signals that may be sensitive to moisture, air or other chemicali nteractions.L ittle attentionh as been paid to chiral recognition based on nucleophilic substitution under mild conditions, [8] which has several advantages compared with probes based on dynamic covalent chemistry,s uch as wide analyte scope and tolerance of air and water.…”

“…Most of the probes operate through mechanisms based on dynamic covalent chemistry, metal complex coordination, and supramolecular chemistry, which generate characteristic optical signals that may be sensitive to moisture, air or other chemical interactions. Little attention has been paid to chiral recognition based on nucleophilic substitution under mild conditions, which has several advantages compared with probes based on dynamic covalent chemistry, such as wide analyte scope and tolerance of air and water.…”