Sustainable synthesis of enantiopure fluorolactam derivatives by a selective direct fluorination – amidase strategy. Issue 5 (19th October 2015) - Willis, Nicky J.
Abstract : Chiral fluorolactam derivatives bearing a fluorine atom at a stereogenic centre were synthesized by a combination of selective direct fluorination using fluorine gas and a biochemical amidase cyclisation process. Abstract : Pharmaceutically important chiral fluorolactam derivatives bearing a fluorine atom at a stereogenic centre were synthesized by a route involving copper catalyzed selective direct fluorination using fluorine gas for the construction of the key C–F bond and a biochemical amidase process for the crucial asymmetric cyclisation stage. A comparison of process green metrics with reported palladium catalyzed enantioselective fluorination methodology shows the fluorination-amidase route to be very efficient and more suitable for scale-up.