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α-Aminonitriles are not only broadly useful building blocks but also structural motifs in bioactive molecules. The Strecker reaction is one of the most widely used methods for α-aminonitrile synthesis. However, a severe drawback in Strecker reactions is the required use of a stoichiometric amount of toxic cyanation reagents. Thus, the development of a greener and widely applicable method for the synthesis of aminonitriles from readily available starting materials presents an important yet unmet challenge. We developed a general and new method for the synthesis of aminonitriles from readily available aminoacetonitrile. This method utilized off-the-shelf ammonium salts as catalysts, tolerated air and moisture, and avoided the use of cyanation reagents, which rendered it a greener alternative to the widely practiced Strecker reaction approach. We further illustrated that chiral ammonium-catalyzed asymmetric reactions of N-arylidene aminoacetonitriles could provide chiral α-tertiary and α-quaternary aminonitriles and α-aminonitriles bearing two continuous stereocenters.

Chiral aminonitriles not only are broadly useful building blocks but also increasingly appear as structural motifs in bioactive molecules and pharmaceuticals. The catalytic asymmetric synthesis of chiral aminonitriles, therefore, has been intensively investigated, as reflected in numerous reports of catalytic asymmetric Strecker reactions. Despite such great progress, the catalytic asymmetric synthesis of chiral a,a-dialkyl aminonitriles in a highly selective and efficient manner is still a formidable challenge. Here, we report a new approach for the catalytic asymmetric synthesis of chiral a,a-dialkyl aminonitriles via reaction of cyanoketimines with enals. We demonstrate that this reaction could be carried out with as low as 20 ppm catalyst loading.

Fluorodesilylation is a widely used strategy to activate organosilanes as nucleophiles for the development of organic transformations. To date, highly enantioselective catalytic fluorodesilylations have been limited to the activation of silyl ethers, organosilanes bearing specific substituents such as trifluoromethyl and cyanide, allylsilanes, and acylsilanes. However, the catalytic enantioconvergent reaction of racemic organosilanes bearing variable substituents via fluorodesilylation has been rarely reported. We report an unprecedented enantioconvergent fluorodesilylation of racemic organosilanes bearing various substituents with a chiral ammonium fluoride. Notably, these results demonstrated that the fluorodesilylation could potentially be a general strategy for the development of catalytic asymmetric reactions of racemic organosilanes.