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Direct Synthesis of Ketones from Methyl Esters by Nickel‐Catalyzed Suzuki–Miyaura Coupling
Author(s) -
Zheng YanLong,
Xie PeiPei,
Daneshfar Omid,
Houk Kendall N.,
Hong Xin,
Newman Stephen G.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202103327
Subject(s) - chemoselectivity , chemistry , aryl , reactivity (psychology) , catalysis , nucleophile , alkyl , catalytic cycle , carbene , ether , amide , bond cleavage , coupling reaction , nickel , combinatorial chemistry , ligand (biochemistry) , functional group , ketone , medicinal chemistry , organic chemistry , medicine , biochemistry , alternative medicine , receptor , polymer , pathology
The direct conversion of alkyl esters to ketones has been hindered by the sluggish reactivity of the starting materials and the susceptibility of the product towards subsequent nucleophilic attack. We have now achieved a cross‐coupling approach to this transformation using nickel, a bulky N‐heterocyclic carbene ligand, and alkyl organoboron coupling partners. 65 alkyl ketones bearing diverse functional groups and heterocyclic scaffolds have been synthesized with this method. Catalyst‐controlled chemoselectivity is observed for C(acyl)−O bond activation of multi‐functional substrates bearing other bonds prone to cleavage by Ni, including aryl ether, aryl fluoride, and N‐Ph amide functional groups. Density functional theory calculations provide mechanistic support for a Ni 0 /Ni II catalytic cycle and demonstrate how stabilizing non‐covalent interactions between the bulky catalyst and substrate are critical for the reaction's success.