title: Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds.
abstract: Amides are common functional groups that have been studied for more than a century. 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. Although amides can readily be cleaved by enzymes such as proteases, 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Hie
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Noah F
authors.initials: NF
authors.lastname: Fine Nathel
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Tejas K
authors.initials: TK
authors.lastname: Shah
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Baker
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Neil K
authors.initials: NK
authors.lastname: Garg
mesh_terms: D000438:Alcohols; D000577:Amides / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry; D001565:Benzoates / Q000138:chemical synthesis; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D004952:Esters / Q000138:chemical synthesis*; D009532:Nickel / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000438:Alcohols; D000577:Amides; D001549:Benzamides; D001565:Benzoates; D004952:Esters; C044605:methyl benzoate; D002244:Carbon; D009532:Nickel; D009584:Nitrogen