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Ketones from Nickel‐Catalyzed Decarboxylative, Non‐Symmetric Cross‐Electrophile Coupling of Carboxylic Acid Esters
Author(s) -
Wang Jiang,
Cary Brian P.,
Beyer Peyton D.,
Gellman Samuel H.,
Weix Daniel J.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201906000
Subject(s) - chemistry , electrophile , ketone , reagent , carboxylic acid , alkyl , aryl , catalysis , reactivity (psychology) , ligand (biochemistry) , organic chemistry , heteroatom , medicinal chemistry , combinatorial chemistry , coupling reaction , medicine , biochemistry , alternative medicine , receptor , pathology
Synthesis of the C−C bonds of ketones relies upon one high‐availability reagent (carboxylic acids) and one low‐availability reagent (organometallic reagents or alkyl iodides). We demonstrate here a ketone synthesis that couples two different carboxylic acid esters, N ‐hydroxyphthalimide esters and S ‐2‐pyridyl thioesters, to form aryl alkyl and dialkyl ketones in high yields. The keys to this approach are the use of a nickel catalyst with an electron‐poor bipyridine or terpyridine ligand, a THF/DMA mixed solvent system, and ZnCl 2 to enhance the reactivity of the NHP ester. The resulting reaction can be used to form ketones that have previously been difficult to access, such as hindered tertiary/tertiary ketones with strained rings and ketones with α‐heteroatoms. The conditions can be employed in the coupling of complex fragments, including a 20‐mer peptide fragment analog of Exendin(9–39) on solid support.