Strategic molecular bridging: Replacement of oxygen with sulfur in C-linked nucleosides can fundamentally alter anomeric reactivity, leading to unexpected and exclusive α-selective cyanation in our w...

Nature Catalysis, Published online: 24 August 2026; doi:10.1038/s41929-026-01598-5C–N bond functionalization of aliphatic primary amines is severely hampered by the poor nucleofugality of the NH2 group. Now, a direct catalytic deaminative cyanation of aliphatic primary amines has been established to enable efficient nitrile synthesis, including an asymmetric variant.

We report the highly enantioselective nucleophilic addition reaction of simple ketone-derived hydrazones. Accordingly, a ErCl₃-catalyzed cyanation of both aliphatic and aryl ketone hydrazones is achieved for the facile access of Cα-tetrasubstituted α-hydrazino nitriles in up to 96% ee, by using the sterically confined pyridinebisoxazoline (PYBOX) ligand featuring a sulfonyl group at the pyridine C4 position. This method enables the shortest catalytic enantioselective total synthesis of L-carbidopa, a drug that could treat the symptoms of Parkinson’s disease, with 82% overall yield in four steps. These adducts are valuable synthons to various α-tertiary hydrazines and related azacycles that are interesting targets for medicinal studies and pesticide research. From our biological analysis, a chiral α-hydrazino nitrile with good insecticidal activity against Aphis gossypii (LC50 = 15.11 mg∙L–1) was identified, rivaling commercial insecticides. Authors present an ErCl₃-catalyzed cyanation

The cyano group is frequently encountered in drug discovery1,2. In 2024, 8 cyano-containing small-molecule drugs, spanning diverse therapeutic areas, were among the top 100 pharmaceutical products by sales3 (Fig. 1a). Although several methods exist for synthesizing nitriles from halides4,5,6, carboxylic acids7,8,9, alcohols10,11,12 and even C–H bonds13,14,15,16,17, the conversion of an amino group to a cyano group is of particular interest. However, direct deaminative functionalization presents several challenges. The C–N bonds in primary amines are typically kinetically inert owing to their low nucleofugality, and amines themselves are basic, nucleophilic and prone to oxidation-induced decomposition18,19,20,21. Historically, prefunctionalization strategies have been required, including converting amines to diazoniums22, Katritzky-type pyridiniums23, redox-active imines24 or isonitriles25. However, these approaches necessitate at least two distinct transformations to achieve a single desired interconversion. Although deaminative cyanation has been achieved using aryldiazonium salts26,27, Katritzky-type pyridiniums28 or benzylic quaternary ammonium salts29, these methods suffer from distinct limitations, such as the need for excess metal reagents, high reaction temperatures or narrow substrate scopes, and no asymmetric variant has been reported so far (Fig. 1d). Despite these synthetic challenges, the direct conversion of C–NH2 to C–CN remains a worthwhile goal. This is because the nitrile group serves as a gateway to a...

Transition metal-catalysed enantioselective radical transformations have emerged as powerful tools for the synthesis of chiral molecules, and a range of methods have been developed. However, most of these successful reactions are effective for resonance-stabilized radicals; in sharp contrast, achieving precise stereocontrol over highly reactive, unstabilized alkyl radicals remains a major challenge, with very few successful examples. Here we establish a ligand-mediated radical orientation strategy that enables the highly enantioselective cyanation of such transient intermediates via copper catalysis. The chiral BoxOH ligand engages in dynamic hydrogen bonding with various remote functional groups on the radical species, strategically reshaping the reaction energy landscape and overcoming the inherently barrierless radical coupling process to dictate stereoselectivity. Consequently, this method enables the direct asymmetric cyano-functionalization of unactivated alkenes and inert sp3 C–H bonds, expanding asymmetric radical reactions beyond stabilized intermediates and providing a platform for the enantioselective functionalization of abundant chemical feedstocks...

Nature Catalysis, Published online: 10 July 2026; doi:10.1038/s41929-026-01573-0Reactions involving transient, unstabilized alkyl C-radicals generally suffer from poor enantioselectivity. Here the authors describe a method for the highly enantioselective cyanation of C-radicals via copper catalysis, enabled by a ligand-mediated radical orientation strategy.

Nature Catalysis, Published online: 10 July 2026; doi:10.1038/s41929-026-01578-9Direct deaminative cyanation of aliphatic amines is hampered by inert C–N bonds and oxidative instability. Now a copper-catalysed, preactivation-free approach enabled by anomeric amide activation is reported that also includes an asymmetric variant.

The route and process for the penultimate intermediate toward an mTOR inhibitor GSK332 in GSK’s respiratory portfolio is described. It relies on a heterocycle formation from a crystalline sodium ketoester enolate and an amidine derived from Pd-catalyzed cyanation of an azaindole. The final step involves an SNAr reaction through selective activation by a hindered sulfonyl chloride and Lewis acid activation to accelerate the rate.

An electrochemical cyanation reaction was developed in the presence of iodine under metal-free and chemical-oxidant-free conditions. Using this synthetic method, a class of cyano-functionalized…

Metal-free β- and Z-selective hydrocyanation of terminal ynamides using TMSCN and TBAF is described. The transformation proceeds with excellent regio- and stereoselectivity, delivering exclusively Z-c...