Remote Anodic Substitution of Ketones

Ketones which lacked branching at the α position were oxidized at ~2.2 V vs. Ag|0.1 M AgNO₃ in acetonitrile. The anolyte was acetonitrile-lithium perchlorate, and the anode was platinum. Substitution of acetamide for hydrogen at remote (γ, δ, ϵ) positions was observed for straight-chain ketones. 2-Hexanone produced 5-acetamido-2-hexanone, 2-heptanone gave mainly 6-acetamido-2-heptanone, and 2-octanone led to a mixture of 5-, 6-, and 7-acetamido-2-octanones. Ketones with branching at the β position gave rearranged ketoamides under these conditions. 4,4-Dimethyl-2-pentanone, for example, gave only 4-acetamido-4-methyl-2-hexanone. The oxidation of 4-deuterio-4-methyl-2-pentanone produced two products: 1-deuterio-2-acetamido-2-methyl-4-pentanone by deuteride migration and 4-deuterio-4-acetamido-2-hexanone by methyl migration. A mechanism involving intramolecular hydrogen abstraction by a ketone cation radical and carbonium ion formation is proposed.