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 has been intensively investigated, as reflected in numerous reports of catalytic asymmetric Strecker reactions. Despite such great progress, the catalytic asymmetric synthesis of chiral α,α-dialkyl aminonitriles in a highly selective and efficient manner is still a formidable challenge.

In a new study, researchers from Prof. Deng Li’s group have reported a new approach for the catalytic asymmetric synthesis of chiral α,α-dialkyl aminonitriles via reaction of cyanoketimines with enals.

Their new approach provides a direct access to chiral α,α-dialkyl aminonitriles, which are not easily accessible via catalytic enantioselective Strecker reaction.

Furthermore, this methodology allowed stereoselective access to more complex chiral aminonitriles, such as those bearing two adjacent stereocenters.

It is noteworthy that this reaction tolerated both trans- and cis-β-substituted enals, thereby allowing asymmetric construction of all possible stereoisomers of chiral aminonitriles bearing two adjacent stereocenters.

The study demonstrates that this reaction could be carried out with as low as 20 ppm catalyst loading, thereby making it potentially useful for large-scale aminonitrile synthesis.

The study, titled “Catalytic Asymmetric Synthesis of Chiral α,α-Dialkyl Aminonitriles via Reaction of Cyanoketimines,” was recently published in the Journal of the American Chemical Society (JACS).

Yuhong Gao, a doctoral candidate at Westlake University’s Department of Chemistry, is the first author. Deng Li, the Xu Yiming Endowed Chair Professor, and Luo Jisheng, Associate Professor, of Westlake University’s Department of Chemistry are the corresponding authors.

The research was supported by the National Natural Science Foundation of China and Foundation of Westlake University, as well as the Instrumentation and Service Center for Molecular Sciences and Physical Sciences at Westlake University.