α-Aminonitriles: From Sustainable Preparation to Applications in Natural Product Synthesis

Due to their numerous reactivity modes, alpha-aminonitriles represent versatile and valuable building blocks in organic total synthesis. Since their discovery by Adolph Strecker in 1850, this compound class has seen a wide dissemination in synthetic applications from laboratory to million-ton industrial scale and was extensively used in the syntheses of various classes of natural products. As these compounds provide a multitude of reactivity options, we feel that a broad overview of their multiple reaction modes may reveal less familiar opportunities for successful total synthesis planning. This personal account article will thus focus on alpha-aminonitriles used as key intermediates in selected natural product synthesis sequences which have been reported in the two decades since Enders' and Shilvock's seminal review. Natural alpha-aminonitriles will also briefly be treated.