JACS: a strategy for the direct construction of C-C bond from inactive C (SP3) - H bond by photo nickel co catalysis reported by Doyle group of Princeton University

The direct functionalization of C-H bonds of inactive alkanes is a challenging subject in organic chemistry C (SP 3) - H bond can be oxidized to form C-X bond (x = O, N, B, f or CL), which can be used as precursor of C (SP 3) - C bond formation reaction In contrast, it is more attractive to form C-C bond directly from the inactive C (SP 3) - H bond However, the excessive use of guiding group and substrate limits the wide application of this strategy Therefore, it is important for organic synthesis to develop the strategy of constructing C-C bond from inactive C (SP 3) - H bond Recently, the Doyle research group of Princeton University developed a method for the formation of C-C bond between unactivated C (SP 3) - H bond and chloroformate catalyzed by Ni and photocatalysis The reaction only needs 3 equivalent alkanes and has a wide range of substrate applicability It can be used for the synthesis of carbonyl derivatives (Figure 1) The results were published in J am Chem SOC (DOI: 10.1021 / JACS 8b09191) (source: J am Chem SOC.) based on previous mechanism studies and literature reports, the author hypothesized that the catalytic cycle of functionalization of C (SP 3) - H bond (Figure 2): (dtbbpy) Ni 0 (1) was first oxidized onto chloroformate derivatives to produce (dtbbpy) Ni II (co 2R) (CL) (2); meanwhile, photocatalyst IR [DF (CF 3) PPy] 2 (dtbbpy) pf 6 (3 ）The excited species 4 was obtained by the irradiation of visible light; 4 was oxidized to the transition state (dtbbpy) Ni III (co 2R) (CL) (5); 5 the elimination reaction occurred under the illumination to produce the chlorine free radical, and the chlorine free radical grabbed the hydrogen of alkane to obtain the carbon free radical; the addition of the carbon free radical to Ni II produced 8; 8 the reduction elimination reaction took place to obtain the product (source: J am Chem SOC.) firstly, the reaction conditions were optimized with the model substrate of benzoyl chloroformate (11) and cyclohexane (Table 1) The optimum reaction conditions are: 0.5 mol% photocatalyst 3, 4 mol% Ni (COD) 2, 5.2 mol% dtbbpy, 2 equivalent K 3PO 4 and 1 equivalent Na 2WO 4 · 2H 2O The yield of the target compound can be 66% when 11 reacts with cyclohexane at 34 ℃ for 48 hours The results show that Ni and IR catalysts and light are necessary for the reaction (source: J am Chem SOC.), the author studied the substrate range of C (SP 3) - H cross coupling reaction (Figure 3) P-fluoro and p-methoxy substituted phenyl chloroformate can react with cyclooctane 4-morpholine carbonyl chloride is also a suitable substrate for direct amidation Cycloalkanes of 5 to 15 membered rings can react with benzoyl chloroformate and obtain the target product (12, 20 - 22) in good yield Tetramethylsilane can also be functionalized successfully, and the target product (24) can be obtained in 51% yield The C-H bonds at α, β and γ positions of n-pentane can be functionalized, and the ratio is 1:8:4.6 Similarly, the ratio of functionalization of 2-methylbutane α, β, γ, δ is 1.3:9:6.3:1 The reactivity of toluene with alkylbenzene was also investigated It was found that toluene and its acyclic and cyclic derivatives can form C-C bond in good yield Under the condition of double catalysis, 4-azacyclobutane and 12 crown ether can be successfully converted into α - aminoester 40 and α - oxyester 43 Cyclic hydrocarbons with electron absorbing functional groups, such as cyclopentanone and cyclopentyl nitrile, can selectively generate β - functionalized products 44 and γ - functionalized products 45 For acyclic ketones, the selectivity of γ - functionalization increases when the reaction site changes from primary position to secondary position In addition, the author also evaluated the application of this method in later functionalization Perilla lactone can selectively react on the most electron rich methylene site and yield 51% in 40% yield The derivative 52 can also be obtained in 18% yield (source: J am Chem SOC.) conclusion: Doyle group of Princeton University in the United States has developed a general strategy of directly obtaining carbonyl derivatives from inactive C (SP 3) - H bonds by using Ni and photocatalysis The reaction has a wide range of substrate applicability.