Selective Metalation and Functionalization of Fluorinated Nitriles Using 2,2,6,6-Tetramethylpiperidyl Bases

Abstract

We have accomplished regioselective deprotometalation of aromatic and heteroaromatic nitriles via (TMP)(2)Zn center dot 2MgCl(2)center dot 2LiCl and TMPMgCl center dot LiCI (TMP = 2,2,6,6-tetramethylpiperidyl) with the exploration of new and scarcely investigated metalation positions. Regioselectivity was rationalized by DFT calculations. The quenching of the generated organozinc and organomagnesium intermediates with various electrophiles gave access to 47 highly functionalized nitriles with yields up to 95%. Additionally, we report a difunctionalization strategy and the use of functionalized nitriles as building blocks to construct relevant heterocycles.