Journal Article

Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds

Hie, Liana, Shah, Tejas K., Hong, Xin, Liu, Peng, Garg, Neil K., Baker, Emma L., Fine Nathel, Noah F., Yang, Yun-Fang, Houk, K. N.

2015

Overview

Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry; now the activation and cleavage of these bonds using nickel catalysts is used to convert amides to esters. Amide C–N bonds activated by nickel catalysis Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. In this paper the authors demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. They used this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. Amides are common functional groups that have been studied for more than a century 1 . They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond 1 , 2 . Although amides can readily be cleaved by enzymes such as proteases 3 , it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon–nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon–heteroatom or carbon–carbon bonds using non-precious-metal catalysis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 119/118 / 140/131 / 140/58 / 639/638/403 / 639/638/77 / Alcohols / Amides / Amides - chemistry / Analysis / Benzamides - chemistry / Benzoates - chemical synthesis / Carbon / Carbon - chemistry / Catalysis / Chemical bonds / Chemical properties / Chemistry Techniques, Synthetic - methods / Conversion / Density functionals / Esters / Esters - chemical synthesis / Humanities and Social Sciences / letter / Ligands / multidisciplinary / Nickel / Nickel - chemistry / Nitrogen / Nitrogen - chemistry / Proteases / Science / Studies / Thermodynamics