A general approach using spiroborate reversible cross-linked Au nanoparticles for visual high-throughput screening of chiral vicinal diols

Abstract

Since enantiopure vicinal diols are important intermediates for the synthesis of numerous pharmaceutical and industrial products, enantioseparation of chiral vicinal diols has received much attention. Here we report a stepwise protocol for creating high-throughput screening (HTS) assays for concentration and enantiomeric excess (ee) of vicinal diols applied to asymmetric dihydroxylation (AD) reactions by using spiroborate reversible cross-linked Au nanoparticles (AuNPs). The enantioselective assays have been demonstrated by NMR spectroscopy and successfully used to rapidly analyze the AD reactions of trans-stilbene with different reaction time and chiral ligands. The first and second steps involve the decoration of a small library of chiral AuNPs with saccharides that possess chiral cis-vicinal diol sites, and verification of the borate-directed assembly and disassembly of the chiral AuNPs. The third step concerns discovery of the optimal chiral AuNPs for a given analyte. The fourth step involves the evaluation of the accuracy and HTS performance of the method. The errors resulting from the analysis of true unknowns are remarkably low, within 2.7% for ee and 0.05 mM for total concentration. The method developed for hydrobenzoin has been applied to analyze the real AD reactions of trans-stilbene. Since the enantioseparation is based on enantioselective ligand exchange (eLE) principle and the reversibility of boron chemistry, this proof of concept approach can be easily adapted to other kinds of asymmetric reactions by using relevant optical nanoprobes.