Nitrile Alkylations through Sulfinyl–Metal Exchange

Abstract

Nitriles play pivotal roles in a diverse range of pharmaceuticals. [1] The nitrile pharmacophore often engages in key hydrogen bonding, as in the blockbuster drug anastrazole (1), [2] in other cases a covalent attachment occurs, as in the anti-diabetic vildagliptin (2, Scheme 1). [3] Syntheses of many nitrile-containing pharmaceuticals, particularly of those bearing quaternary centers, such as anastrazole [1] and the cyclohexylnitriles levocabastine (3) [4] and cilomilast (4), [5] typically involve multiple alkylations.