Nucleophilic Fluorination Catalyzed by a Cyclometallated Rhodium Complex

Patrick J Morgan; Graham C Saunders; Stuart A Macgregor; Andrew C Marr; Peter Licence

doi:10.1021/acs.organomet.2c00052

Nucleophilic Fluorination Catalyzed by a Cyclometallated Rhodium Complex

Organometallics. 2022 Apr 11;41(7):883-891. doi: 10.1021/acs.organomet.2c00052. Epub 2022 Mar 31.

Authors

Patrick J Morgan¹, Graham C Saunders², Stuart A Macgregor³, Andrew C Marr⁴, Peter Licence¹

Affiliations

¹ GSK Carbon Neutral Laboratory, School of Chemistry, University of Nottingham, Nottingham NG7 2TU, U.K.
² School of Science, University of Waikato, Hamilton 3240, New Zealand.
³ School of Engineering and Physical Sciences, Heriot-Watt University, William H. Perkin Building, Edinburgh EH14 4AS, U.K.
⁴ School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Belfast BT9 5AG, U.K.

Abstract

Quantitative catalytic nucleophilic fluorination of a range of acyl chlorides to acyl fluorides was promoted by a cyclometallated rhodium complex [(η⁵,κ₂C-C₅Me₄CH₂C₆F₅CH₂NC₃H₂NMe)- RhCl] (1). 1 can be prepared in high yields from commercially available starting materials using a one-pot method. The catalyst could be separated, regenerated, and reused. Rapid quantitative fluorination generated the fluoride analogue of the active pharmaceutical ingredient probenecid. Infrared in situ monitoring verified the clean conversion of the substrates to products. VTNA graphical kinetic analysis and DFT calculations lead to a postulated reaction mechanism involving a nucleophilic Rh-F bond.