Sustainable synthesis of enantiopure fluorolactam derivatives by a selective direct fluorination – amidase strategy

Willis, N.J.; Fisher, C.A.; Alder, C.M.; Harsanyi, A.; Shukla, L.; Adams, J.P.; Sandford, G.

doi:10.1039/c5gc02209f

Sustainable synthesis of enantiopure fluorolactam derivatives by a selective direct fluorination – amidase strategy

Willis, N.J.; Fisher, C.A.; Alder, C.M.; Harsanyi, A.; Shukla, L.; Adams, J.P.; Sandford, G.

Authors

N.J. Willis

C.A. Fisher

C.M. Alder

A. Harsanyi

L. Shukla

J.P. Adams

G. Sandford

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.

Citation

Willis, N., Fisher, C., Alder, C., Harsanyi, A., Shukla, L., Adams, J., & Sandford, G. (2016). Sustainable synthesis of enantiopure fluorolactam derivatives by a selective direct fluorination – amidase strategy. Green Chemistry, 18(5), 1313-1318. https://doi.org/10.1039/c5gc02209f

Journal Article Type	Article
Acceptance Date	Oct 13, 2015
Online Publication Date	Oct 13, 2015
Publication Date	Mar 7, 2016
Deposit Date	Oct 21, 2015
Publicly Available Date	Oct 13, 2016
Journal	Green Chemistry
Print ISSN	1463-9262
Electronic ISSN	1463-9270
Publisher	Royal Society of Chemistry
Peer Reviewed	Peer Reviewed
Volume	18
Issue	5
Pages	1313-1318
DOI	https://doi.org/10.1039/c5gc02209f