High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening

Elena G. Shcherbakova, Valentina Brega, Vincent M. Lynch, Tony D. James, Pavel Anzenbacher

Research output: Contribution to journalArticle

15 Citations (Scopus)
165 Downloads (Pure)

Abstract

A simple and efficient method for determination of the yield, enantiomeric/diasteriomeric excess (ee/de), and absolute configuration of crude chiral diols without the need of work-up and product isolation in a high throughput setting is described. This approach utilizes a self-assembled iminoboronate ester formed as a product by dynamic covalent self-assembly of a chiral diol with an enantiopure fluorescent amine such as tryptophan methyl ester or tryptophanol and 2-formylphenylboronic acid. The resulting diastereomeric boronates display different photophysical properties and allow for fluorescence-based ee determination of molecules containing a 1,2- or 1,3-diol moiety. This method has been utilized for the screening of ee in a number of chiral diols including atorvastatin, a statin used for the treatment of hypercholesterolemia. Noyori asymmetric hydrogenation of benzil was performed in a highly parallel fashion with errors <1 % ee confirming the feasibility of the systematic examination of crude products from the parallel asymmetric synthesis in real time and in a high-throughput screening (HTS) fashion.

Original languageEnglish
Pages (from-to)10222-10229
Number of pages8
JournalChemistry - A European Journal
Volume23
Issue number42
Early online date6 Jul 2017
DOIs
Publication statusPublished - 26 Jul 2017

Keywords

  • asymmetric catalysis
  • diols
  • enantiomeric excess
  • fluorescence
  • self-assembly

ASJC Scopus subject areas

  • Chemistry(all)

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