Enantioselective electrophilic fluorination: a study of the fluorine-transfer from achiral N–F reagents to cinchona alkaloids

Abstract

A transfer fluorination on cinchona alkaloids with the aid of achiral N–F fluorine-transfer reagents is described. Ten commercially available reagents were evaluated. Selectfluors™ 9 and 10, Accufluor™ 11, N-fluorobenzenesulfonimide (NFSi) 13, and N-fluoro-2,6-dichloropyridinium tetrafluoroborate 17 are effective fluorine-transfer reagents. The N-fluoroammonium salts of cinchona alkaloids thus prepared were employed in the construction of stereogenic fluorinated carbon centers with enantioselectivity as high as 85%. We also demonstrated that ionic liquids are effective “green” solvents for the development of this methodology.