Direct arylation of strong aliphatic C-H bonds

Article

关键词: HYDROGEN-ATOM TRANSFER;    DECATUNGSTATE ANION;    FUNCTIONALIZATION;    NICKEL;    DEHYDROGENATION;    ALKYLATION;    CATALYSIS;    PRODUCTS;    ALKANES;   

DOI  :  10.1038/s41586-018-0366-x

来源: SCIE

【 摘 要 】

Despite the widespread success of transition-metal-catalysed cross-coupling methodologies, considerable limitations still exist in reactions at sp(3)-hybridized carbon atoms, with most approaches relying on prefunctionalized alkylmetal or bromide coupling partners(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(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(3))-heteroatom bonds from strong C-H bonds has been reported(6-7). Additionally, valuable technologies have been developed for the formation of carbon-carbon bonds from the corresponding C(sp(3))-H bonds via substrate-directed transitionmetal C-H insertion(8), undirected C-H insertion by captodative rhodium carbenoid complexes', or hydrogen atom transfer from weak, hydridic C-H bonds by electrophilic open-shell species(10-14). Despite these advances, a mild and general platform for the coupling of strong, neutral C(sp(3))-H bonds with aryl electrophiles has not been realized. Here we describe a protocol for the direct C(sp(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(3))-C(sp(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.

【 授权许可】

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