Iscience: report on the synthesis of carbonylalkyliodide catalyzed by nickel

Alkyl iodine is a common block in organic chemistry and drug synthesis The cleavage and functionalization of ethers are common reactions in organic synthesis However, due to the high bond energy of C-O bond, these transformations usually require relatively stringent reaction conditions In addition to the use of transition metal catalyzed carbon monoxide insertion to synthesize carbonyl compounds, alcohols, amines, alkynes and other nucleophiles and organometallic compounds are often used as substrates for carbonylation coupling reactions However, studies on Carbonylation Coupling of weak nucleophiles, such as aromatics and ethers, have rarely been reported Especially, it has not been reported that ether with lower reactivity is used as nucleophilic reagent for carbonylation Recently, a nickel catalyzed C-O bond cleavage carbonylation of aryl iodide and ether was reported by Professor Wu Xiaofeng of Zhejiang University of science and technology Mo (CO) 6 was used as solid Co source for the synthesis of various functionalized carbonyl alkyliodides Relevant research results were published in iscience (DOI: 10.1016 / j.isci 2018.09.024) Firstly, iodobenzene 1a and tetrahydrofuran 2B were selected as the model substrates of carbonylation ring opening reaction to screen the reaction conditions (Table 1) In the presence of 1 equivalent mo (CO) 6, 5 mol% NiCl 2 and 5 mol% dtbbpy, the ring opening reaction of carbonylation can be carried out successfully with toluene as solvent, and the target product δ - butyl iodobenzoate 3AB can be obtained in 52% yield Temperature plays an important role in the reaction Increasing the reaction temperature will promote the oxidation of transition metals on the C-I bond and the decomposition of Mo (CO) 6 to release Co, resulting in the reduction of the reaction yield Higher reaction temperature will lead to decarbonylation of nickel acyl complex The results show that the combination of Ni (OTF) 2 and dtbbpy has a good catalytic effect In the presence of 0.5 equivalent mo (CO) 6, the yield of 3AB can reach 64% In addition, the solvent has a great influence on the carbonylation reaction When the reaction is carried out in xylene and cyclohexane, the yield is reduced to 57% and 42%; when chlorobenzene is used as the solvent, the yield is significantly increased to 89% This may be due to the high polarity of chlorobenzene and the high solubility of the substrate The yield can be further increased to 93% by adding tetrahydrofuran to 3 equivalent However, when using gaseous CO (1 ATM) instead of Mo (CO) 6, no product was obtained (picture source: iscience) further, the author studied the substrate range of aryl iodide (Figure 1) The results showed that the iodobenzene substituted by donor (3AB, 3ib) and acceptor (3jb - 3qb) groups was well tolerated The steric hindrance of iodobenzene can significantly affect the yield of the reaction M-and p-substituted iodobenzene has good yields (3CB, 3dB, 3Nb and 3MB) The yield of o-methyliodobenzene is only 51%, and the yield of o-chloroiodobenzene is only trace Ketone, ester, fluorine, chlorine and other functional groups have good tolerance In addition to substituted iodobenzene, other aryl iodides, such as 1-iodobenzene, 2-iodobenzene and 3-Iodothiophene, are also suitable substrates (3Rb, 3Sb and 3TB) However, bromobenzene and 1- bromo -4- (trifluoromethyl) benzene could not be transformed (image source: iscience) then, the author examined the substrate range of ether (Figure 2) As shown in the figure, cyclic and acyclic ethers also showed good tolerance in the reaction system Symmetrical cyclic ethers, such as tetrahydropyran 2C and 7-oxo-heterobicyclo [2.2.1] heptane, are well tolerated for 2D, and the products 3aC and 3hd can be obtained in medium yields However, when the reaction temperature rises to 140 ℃, the yield of 3HA 'can be increased to 41% The cleavage of asymmetric cyclic ether may be carried out by two different C-O bond cleavage modes Generally, C-O bond cleavage takes place preferentially on the carbon with larger space volume For example, the ring opening product 3af of 2-methyltetrahydrofuran 2F is the main product (3af: 3af '= 9:1) 2,3-dihydrobenzofuran 2E can also produce ring opening product 3aE in 37% yield In addition, it was found that the corresponding esters (3ah, 3AI and 3aj) could be obtained by the reactions of ether, butyl ether and isopropyl ether (picture source: iscience) in order to better understand the mechanism of decomposition carbonylation of the ether, the author designed a series of control experiments (scheme 1) First of all, in the presence of excessive halide additives such as LiCl and LiBr, iodobenzene 1a and tetrahydrofuran 2B can obtain iodate 3A B in high yield, and there is no chlorination or bromination in the reaction In addition, when dioxane 2m was used as the substrate, the reaction did not produce 3 am of iodized products This may be due to the coordination of 3am with nickel catalyst to promote the carbonylation of the second ether cracking When asymmetric ether 2F reacts with iodobenzene, 3af and 3af 'are obtained in the ratio of 9:1 The ratio of benzoyl iodine and 2-methyltetrahydrofuran 2F is 1:2 This shows that the carbonylation of ether decomposition is not carried out through the intermediate acyl iodine, and the ester formation step and the iodine connection step should be carried out in coordination (picture source: iscience) finally, the author put forward a reasonable reaction mechanism (scheme 2) At first, Ni (0) in situ was oxidized and added by aryliodide to form the aryl nickel complex 4 Then, the co released by Mo (CO) 6 is inserted to produce the acyl nickel complex 5, which is coordinated with the oxygen of tetrahydrofuran to obtain the intermediate 6 whose C-O bond is activated The C-O bond breaks to produce intermediate 7 Finally, the required product 3 was eliminated by 7 reduction and then Ni (0) was formed Conclusion: Professor Wu Xiaofeng of Zhejiang University of science and technology has developed an interesting nickel catalyzed carbonylation reaction Mo (CO) 6 was used as the solid Co source for the reaction, which had good substrate range and functional group tolerance.