Mild and Selective Activation and Substitution of Strong Aliphatic CF Bonds

A procedure for chemoselectively manipulating the strong aliphatic CF bond with direct transformation into a CN bond under mild conditions is reported. The activation and subsequent substitution of primary alkyl fluorides is mediated by La[N(SiMe 3 ) 2 ] 3 , and results in high to excellent yields of tertiary amines. The methodology displays high selectivity towards the C(sp 3 )F bond, and a variety of secondary amines are applicable as nucleophiles. Mechanistic investigations reveal a reaction that is first order with respect to [La[N(SiMe 3 ) 2 ] 3 ], [R 1 R 2 NH], and [alkyl fluoride], and a 6‐membered cyclic transition state is proposed. In addition, 1 H NMR spectroscopy shows that La[N(SiMe 3 ) 2 ] 3 is the active species involved in the substitution and that protonolysis of the amine, yielding La[NR 1 R 2 ] 3 , lowers the reactivity.