Surface modification

Allylic rearrangement

Enantioselective synthesis

Physical chemistry

Catalysis

Organic chemistry

Chemistry

Steric effects

Combinatorial chemistry

Alkene

Cyanation

Bond cleavage

Molecule

Total synthesis

Stereochemistry

Nature

Methods for selective C–H bond functionalization have provided chemists with versatile and powerful toolboxes for synthesis, such as the late-stage modification of a lead compound without the need for lengthy de novo synthesis1–5. Cleavage of an sp3 C–H bond via hydrogen atom transfer (HAT) is particularly useful, given the large number of available HAT acceptors and the diversity of reaction pathways available to the resulting radical intermediate6–17. Site-selectivity, however, remains a formidable challenge, especially among sp3 C–H bonds with comparable properties. If the intermediate radical could be further trapped enantioselectively, this should enable highly site- and enantioselective functionalization of C–H bonds. Here we report a copper (Cu)-catalysed site- and enantioselective allylic C–H cyanation of complex alkenes, in which a Cu(ii)-bound nitrogen (N)-centred radical plays the key role in achieving precise site-specific HAT. This method is shown to be effective for a diverse collection of alkene-containing molecules, including sterically demanding structures and complex natural products and pharmaceuticals. A Cu-bound nitrogen-centred radical is used to control site-specific and enantioselective allylic C–H cyanations of molecules with synthetic and medicinal relevance, such as tri- and tetrasubstituted alkenes.

Site-specific allylic C–H bond functionalization with a copper-bound N-centred radical