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    Home > Angelw: Paul knockel team reported the cross coupling reaction of (hetero) aryl halides with functionalized alkylzinc reagents catalyzed by cobalt

    Angelw: Paul knockel team reported the cross coupling reaction of (hetero) aryl halides with functionalized alkylzinc reagents catalyzed by cobalt

    • Last Update: 2020-01-23
    • Source: Internet
    • Author: User
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    The method of constructing new C-C bond by transition metal catalysis is very important in organic chemistry and widely used in academic and industrial fields Negishi cross coupling is one of the common methods to form C-C bond to prepare highly functional skeleton Although there are many reports about the cross coupling reaction of csp2-csp3 catalyzed by palladium or nickel, it is still necessary to develop a cheaper and more abundant alternative catalytic system Compared with palladium, cobalt is cheaper, and in most reactions, cobalt catalyst system is efficient and does not need complex ligands In addition, the previously reported methods show that cobalt salts are particularly suitable for catalytic reactions of organic zinc reagents as nucleophilic coupling agents, such as acylation, cross coupling or amination Recently, a team of Professor Paul knockel from the University of Munich, Germany, reported the cross coupling reaction of cobalt catalyzed alkylzinc reagents with a variety of (hetero) aryl and alkynyl halides The related research results were published in angelw Chem Int ed (DOI: 10.1002/anie.201914490) At first, the author screened the reaction conditions with (2 - (1,3-dioxo-2-yl) ethyl) zinc chloride (2a) and 6-chloronicotinic nitrile (1a) model substrates (Table 1) Firstly, the author investigated different metal halides, such as MnCl 2, CuCl 2, FeCl 2, etc., but they did not promote the reaction (entries 2-5) NiCl2 and CoCl2 are suitable catalysts The target product 3A (entries 6, 7) was obtained in 51% and 52% yields respectively The yield of 2,2 '- bipyridine was increased to 66% (entries8-12) By increasing the amount of ligands, 3A (entry 12) can be obtained with the highest yield of 75% (source: angelw Chem Int ed.) under the optimal reaction conditions, the author investigated the universality of the reaction (scheme 1) A variety of alkylzinc reagents with different functional groups (such as alkenyl, alkynyl, cyano) are suitable substrates, and the alkylated pyridine 3B - 3G is obtained in good yield In addition, other N-heterocyclic halides, such as quinoline, isoquinoline, quinazoline and pyrimidine derivatives, can also be successfully cross coupled with a variety of alkyl zinc reagents, thus obtaining the product 3l-3s in 58-95% yield (source: angelw Chem Int ed.) then, the author extended the cobalt catalyzed cross coupling to various electron deficient aryl halides (scheme 2) The aromatic rings with cyano and ester groups were coupled with zinc chloride 2a to obtain 3T - 3U in good yield Halobenzophenone can also react with a variety of zinc reagents to obtain the corresponding product 3V - 3Z in 70% - 85% yield (source: angelw Chem Int ed.) was encouraged by the above experimental results Then, the applicability of CO catalyzed non enantioselective csp3-csp2 Negishi type cross coupling reaction (scheme 3) was investigated Pyridine and pyrimidine bromide substituted by electron absorption group can react smoothly with a variety of cyclohexyl zinc iodide, and the corresponding coupling product 3AA - 3ah can be obtained with good yield and excellent Dr value It is worth noting that 2-bromopyrimidine can also be coupled with the alkyl zinc reagents derived from steroids and sesquiterpenes to obtain the products 3Al and 3aj (scheme 4) with high enantioselectivity (source: angelw Chem Int ed.) (source: angelw Chem Int ed.) finally, the author further extended the range of substrates to alkynyl bromide (scheme 5) Alkylalkyne 5A and 5b can be obtained by the reaction of phenyl or tips substituted bromoacetylene with zinc reagents 2a and 2D, respectively (source: angelw Chem Int ed.) in a word, the author reported the cross coupling reaction of various substituted (primary, secondary) alkylzinc reagents with aryl or heteroaryl halides catalyzed by cobalt When 1,3 - and 1,4-functionalized cyclohexyl zinc reagents are used for coupling, the enantioselectivity of the product can reach 98:2 In addition, the coupling reaction between alkynyl zinc reagent and alkynyl bromide was realized.
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