Abstract
Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far‐reaching impact across synthetic chemistry and the biomedical sciences. Herein, we report an approach to heteroaromatic C−H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, followed by elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring. This one‐pot protocol is simple to perform, is applicable to a broad range of decorated 6‐ring N‐containing heterocycles, and has been shown to be suitable for late‐stage functionalization of complex drug‐like architectures.
Highlights
Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo
Despite the many advances in the field, we recognized that the development of a complementary and direct CÀH cyanation protocol that was general to many classes of N-containing heterocycles would likely find application in library generation and target synthesis, and we report our findings
We were delighted to see that this practical, one-pot protocol was effective across a diverse range of heteroaromatic ring systems, giving aromatic cyanated products in up to 96 % yield (Scheme 2 a)
Summary
Bryony L. Elbert,[a] Alistair J. M. Farley+,[a] Timothy W. Gorman+,[a] Tarn C. Johnson+,[a] Christophe Genicot,[b] BØnØdicte Lallemand,[b] Patrick Pasau,[b] Jakub Flasz,[c] JosØ L. Castro,[c] Malcolm MacCoss,[d] Robert S. Paton,*[a] Christopher J. Schofield,*[a] Martin D. Smith,*[a] Michael C. Willis,*[a] and Darren J. Dixon*[a]
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