Copper-Catalyzed Aerobic Oxidative C-C Bond Cleavage for C-N Bond Formation: From Ketones to Amides

Tang, C.; Jiao, N.; Angew. Chem. Int. Ed. 2014, Early view.

DOI:10.1002/anie.201403528

A novel copper-catalyzed aerobic oxidative C(CO)-C(alkyl) bond cleavage reaction of aryl alkyl ketones for C-N bond formation is described. A series of acetophenone derivatives as well as more challenging aryl ketones with long-chain alkyl substituents could be selectively cleaved and converted into the corresponding amides, which are frequently found in biologically active compounds and pharmaceuticals.

Recently, aerobic oxidative C-C bond cleavage of carbonyl compounds have been reported. Jiang and co- workers reported a transition-metal-free aerobic oxidative C-C bond cleavage of alpha-hydroxyketones and subsequent esterification.^[1] The group of Bi and Liu reported a copper-catalyzed C(CO)-C(methyl) bond cleavage reaction under oxygen atmosphere, which terminates at the aldehyde stage without over oxidization.^[2]

In this time, Jiao group developed a novel copper-catalyzed aerobic oxidative C-C bond cleavage reaction for C-N bond formation,which enables the direct transformation of aryl alkyl ketones into benzamides with high efficiency.

References

[1] “Transition-Metal-Free Aerobic Oxidative Cleavage of C-C Bonds in α-Hydroxy Ketones and Mechanistic Insight to the Reaction Pathway”

Liu, H.; Dong, C.; Zhang, Z.; Wu, P. Jiang, X. Angew. Chem. Int. Ed. 2012, 51, 12570. DOI: 10.1002/anie.201207206

Clear cut: For the title reaction, O₂, the ideal oxidant, was used as the only oxidizing reagent. The dimer intermediate (see scheme) and isotopic labeling control experiments with¹⁸O₂ partially disclosed the reaction mechanism.

[2] “Chemoselective Oxidative C(CO)-C(methyl) Bond Cleavage of Methyl Ketones to Aldehydes Catalyzed by CuI with Molecular Oxygen”

Zhang, L.; Bi, X.; Guan, X.; Li, X.; Lin, Q.; Barry, B.-D., Liao, P. Angew. Chem. Int. Ed. 2013, 52, 11303–11307. DOI:10.1002/anie.201305010

Aldehyde Termination: A novel copper-catalyzed transformation from methyl ketones into aldehydes has been accomplished. This method is applicable to a wide range of aromatic and aliphatic methyl ketones and chemoselectively produces aldehydes, accompanied by the release of hydrogen (H₂) and carbon dioxide (CO₂) as by-products.

Related Books

[amazonjs asin=”B00BLQYKGM” locale=”US” title=”Transition Metal Organometallic Chemistry (SpringerBriefs in Molecular Science)”][amazonjs asin=”364234285X” locale=”US” title=”Inventing Reactions (Topics in Organometallic Chemistry)”]