Synthesis of (2S,4S)‑5,5,5,5′,5′-Pentafluoroleucine and (2S,4R)‑5,5,5-Trifluoroleucine via Stereoselective Hydrogenation and Hydrodefluorination

We describe the synthesis of two challenging fluorinated amino acids, (2S,4S)-5,5,5,5′,5′-pentafluoroleucine and (2S,4R)-5,5,5-trifluoroleucine. The difficulty in synthesizing stems in part from the presence of two chiral centers. Herein, we report the stereoselective hydrogenation and hydrodefluorination of a pentafluoroisobutenyl chain using a chiral Schiff base Ni(II) complex. Depending on the hydrogen pressure, the reaction favors either the formation of a pentafluorinated or trifluorinated chain. This method provides access to enantiopure novel (2S,4S)-5,5,5,5′,5′-pentafluoroleucine and (2S,4R)-5,5,5-trifluoroleucine.