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Author(s): Ian B. Perry [sup.1] , Thomas F. Brewer [sup.1] , Patrick J. Sarver [sup.1] , Danielle M. Schultz [sup.2] , Daniel A. DiRocco [sup.2] , David W. C. MacMillan [...], Despite the widespread success of transition-metal-catalysed cross-coupling methodologies, considerable limitations still exist in reactions at sp.sup.3-hybridized carbon atoms, with most approaches relying on prefunctionalized alkylmetal or bromide coupling partners.sup.1,2. Although the use of native functional groups (for example, carboxylic acids, alkenes and alcohols) has improved the overall efficiency of such transformations by expanding the range of potential feedstocks.sup.3-5, the direct functionalization of carbon-hydrogen (C-H) bonds--the most abundant moiety in organic molecules--represents a more ideal approach to molecular construction. In recent years, an impressive range of reactions that form C(sp.sup.3)-heteroatom bonds from strong C-H bonds has been reported.sup.6,7. Additionally, valuable technologies have been developed for the formation of carbon-carbon bonds from the corresponding C(sp.sup.3)-H bonds via substrate-directed transition-metal C-H insertion.sup.8, undirected C-H insertion by captodative rhodium carbenoid complexes.sup.9, or hydrogen atom transfer from weak, hydridic C-H bonds by electrophilic open-shell species.sup.10-14. Despite these advances, a mild and general platform for the coupling of strong, neutral C(sp.sup.3)-H bonds with aryl electrophiles has not been realized. Here we describe a protocol for the direct C(sp.sup.3) arylation of a diverse set of aliphatic, C-H bond-containing organic frameworks through the combination of light-driven, polyoxometalate-facilitated hydrogen atom transfer and nickel catalysis. This dual-catalytic manifold enables the generation of carbon-centred radicals from strong, neutral C-H bonds, which thereafter act as nucleophiles in nickel-mediated cross-coupling with aryl bromides to afford C(sp.sup.3)-C(sp.sup.2) cross-coupled products. This technology enables unprecedented, single-step access to a broad array of complex, medicinally relevant molecules directly from natural products and chemical feedstocks through functionalization at sites that are unreactive under traditional methods.Direct coupling of aliphatic C-H nucleophiles to aryl electrophiles is described, through the combination of light-driven polyoxometalate hydrogen atom transfer and nickel catalysis.

Author(s): Emily B. Corcoran, Danielle M. Schultz Author Affiliations: Manganese catalyst enables exploration of the magic methyl effect Developing a small-molecule drug requires iterations of building and testing new compounds [...], The addition of a methyl group to a drug molecule can greatly alter the drug's pharmacological properties. A catalyst has been developed that enables this 'magic methyl effect' to be rapidly explored for drug discovery. Late-stage functionalization of complex organic molecules.

The beneficial properties of many medicines, materials and consumer products composed of small organic molecules are greatly influenced by the locations and types of chemical groups within those molecules--especially 'functional' [...]