A Flash Thermal Racemization Protocol for the Chemoenzymatic Dynamic Kinetic Resolution and Stereoinversion of Chiral Amines
Matthew J. Takle, Benjamin J. Deadman, Klaus Hellgardt, Joachim Dickhaut, Andy Wieja, King Kuok Hii
Abstract
High Resolution Image Download MS PowerPoint Slide 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.