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 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.