16219-90-2Relevant articles and documents
Coupling of Challenging Heteroaryl Halides with Alkyl Halides via Nickel-Catalyzed Cross-Electrophile Coupling
Hansen, Eric C.,Li, Changfeng,Yang, Sihang,Pedro, Dylan,Weix, Daniel J.
, p. 7085 - 7092 (2017)
Despite their importance, the synthesis of alkylated heterocycles from the cross-coupling of Lewis basic nitrogen heteroaryl halides with alkyl halides remains a challenge. We report here a general solution to this challenge enabled by a new collection of ligands based around 2-pyridyl-N-cyanocarboxamidine and 2-pyridylcarboxamidine cores. Both primary and secondary alkyl halides can be coupled with 2-, 3-, and 4-pyridyl halides as well as other more complex heterocycles in generally good yields (41 examples, 69% ave yield).
Micelle enabled C(sp2)-C(sp3) cross-electrophile coupling in waterviasynergistic nickel and copper catalysis
Ye, Ning,Wu, Bin,Zhao, Kangming,Ge, Xiaobin,Zheng, Yu,Shen, Xiaodong,Shi, Lei,Cortes-Clerget, Margery,Regnier, Morgan Louis,Parmentier, Michael,Gallou, Fabrice
supporting information, p. 7629 - 7632 (2021/08/09)
A robust and sustainable C(sp2)-C(sp3) cross-electrophile coupling was developedvianickel/copper synergistic catalysis under micellar conditions. This protocol provided a general method to access alkylated arenes with good to excellent yields on a very large scale.
Direct arylation of strong aliphatic C–H bonds
Perry, Ian B.,Brewer, Thomas F.,Sarver, Patrick J.,Schultz, Danielle M.,DiRocco, Daniel A.,MacMillan, David W. C.
, p. 70 - 75 (2018/08/09)
Despite the widespread success of transition-metal-catalysed cross-coupling methodologies, considerable limitations still exist in reactions at sp3-hybridized carbon atoms, with most approaches relying on prefunctionalized alkylmetal or bromide coupling partners1,2. 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 feedstocks3–5, 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(sp3)–heteroatom bonds from strong C–H bonds has been reported6,7. Additionally, valuable technologies have been developed for the formation of carbon–carbon bonds from the corresponding C(sp3)–H bonds via substrate-directed transition-metal C–H insertion8, undirected C–H insertion by captodative rhodium carbenoid complexes9, or hydrogen atom transfer from weak, hydridic C–H bonds by electrophilic open-shell species10–14. Despite these advances, a mild and general platform for the coupling of strong, neutral C(sp3)–H bonds with aryl electrophiles has not been realized. Here we describe a protocol for the direct C(sp3) 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(sp3)–C(sp2) 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.
