Cobalt-catalyzed C-H Bond Activation of Benzamides

In the past ten years, electrochemical methods have become a hot spot in the research of modern organic synthetic chemistry and have been widely used in many fields. Compared with the traditional method of multi-step functional group interconversion, the electrooxidative C–H bond activation strategy combined with the hydrogen evolution reaction (HER) does not require the use of stoichiometric oxidants, and has potential applications for the later transformation of organic compounds.

Recently, some researchers have successfully realized the highly chemoselective, regioselective and enantioselective C-H bond cyclization, N-H bond cyclization and C-H bond etherification of phosphoramidites in benzamides.

First, the researchers chose benzamides and alkenes as model substrates, and cobalt acetate and S-BINOL phosphoric acid as the catalytic system to optimize the conditions of the spirocyclization reaction. Subsequently, the researchers screened various additives and found that pivalic acid could significantly increase the yield while maintaining enantioselectivity, and molecular hydrogen was detected by GC analysis. Under optimal conditions, the researchers explored the range of substrates, and the results showed that benzamides with different electron-withdrawing, electron-donating and oxidizable thioether substitutions on the benzene ring, and maleimide substrates with different group on the N atom are compatible with this reaction, and the desired product is obtained in moderate yield and excellent enantioselectivity.

Next, the researchers used benzamides and unactivated alkenes as model substrates to optimize the conditions for the carboamination reaction of alkenes. The results showed that the ligand derived from L-valine had the best effect, and it could be obtained at room temperature with high yield. A series of chiral dihydroisoquinolinones were obtained with high efficiency and excellent enantioselectivity. It is worth mentioning that this reaction can also be prepared on a deca-gram scale without reducing the yield and enantioselectivity of the reaction, and the Faradaic efficiency of the reaction is 89%, which indicates that the provided electric energy can be effectively utilized.

Finally, the researchers realized the desymmetrization of phosphonamidites and obtained various acyclic chiral phosphonamidites with high enantioselectivity. In addition, C-H bond and N-H bond-activated alkyne cycloaddition reactions can also be desymmetrized, and internal alkynes and phenylacetylenes can be converted to the desired products in good yields and excellent enantioselectivities. Notably, renewable solar energy generated from commercially available photovoltaic cells can also be catalyzed by HER-coupled electrocobalt oxides, further demonstrating the utility of this approach.

Using the catalytic strategy of electrooxidation of Co, the researchers successfully achieved high chemoselectivity, regioselectivity, and enantioselective C-H bond cyclization, N-H bond cyclization and other reactions of benzamides substrates. This strategy produces molecular hydrogen as the only by-product through HER, which is expected to find wide application in organic synthesis.