A Flash Thermal Racemization Protocol for the Chemoenzymatic Dynamic Kinetic Resolution and Stereoinversion of Chiral Amines

A highly practical and effective ‘Flash Thermal Racemization’ (FTR) protocol was developed in continuous flow, without needing a base or a H donor. This can be integrated with an enzyme to enable the chemoenzymatic kinetic resolution of primary amines to be achieved in a more atom-efficient manner w...

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Bibliographic Details
Published inACS catalysis Vol. 13; no. 16; pp. 10541 - 10546
Main Authors Takle, Matthew J., Deadman, Benjamin J., Hellgardt, Klaus, Dickhaut, Joachim, Wieja, Andy, Hii, King Kuok Mimi
Format Journal Article
LanguageEnglish
Published American Chemical Society 18.08.2023
Subjects
chiral amines
design-of-experiment optimization
stereochemical inversion
dynamic kinetic resolution
continuous flow synthesis
flash thermal racemization
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Summary:A highly practical and effective ‘Flash Thermal Racemization’ (FTR) protocol was developed in continuous flow, without needing a base or a H donor. This can be integrated with an enzyme to enable the chemoenzymatic kinetic resolution of primary amines to be achieved in a more atom-efficient manner without additives. An unprecedented space-time yield of up to 1362 μmol mL–1 h–1 can be achieved for the dynamic kinetic resolution of 1-aminoindane, which is at least 10 times more productive than previously reported, and up to 1700-fold more productive when the Pd catalyst loading is taken into account. With a slight modification, the flow reactor system can also be used to convert an optically active amine to its opposite enantiomer.
ISSN:2155-5435
2155-5435
DOI:10.1021/acscatal.3c02859