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High‐Throughput Assay for Enantiomeric Excess Determination in 1,2‐ and 1,3‐Diols and Direct Asymmetric Reaction Screening
Author(s) -
Shcherbakova Elena G.,
Brega Valentina,
Lynch Vincent M.,
James Tony D.,
Anzenbacher Pavel
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201701923
Subject(s) - enantiopure drug , chemistry , enantiomeric excess , moiety , enantioselective synthesis , diol , diastereomer , enantiomer , yield (engineering) , combinatorial chemistry , amine gas treating , organic chemistry , catalysis , materials science , metallurgy
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.