Regiochemical Reversals in Nitrosobenzene Reactions with Carbonyl Compounds: α-Aminooxyketone versus α-Hydroxyaminoketone Products.

The Lewis acid-catalyzed reaction of nitrosobenzene with a ketone can produce an α-aminooxyketones or an α-hydroxyaminoketone, with reaction regiochemistry switching from the latter to the former, dependent upon the addition of Lewis acid or sterically-hindered solvent. While the latter (C-N bond formation) is easily explained by attack of the enolate α-carbon at N, the former (C-O bond formation) has been an enigma, with few proposed explanations, and none which explain simultaneously formation of both products and all the regiochemical reversals. Herein, the regiochemistry reversal is proposed to occur via (1) nucleophile formation governed by Hard and Soft Acids and Bases (HSAB) theory, (2) a nucleophilic attack by the enolate O at N, followed by (3) a [2,3]-sigmatropic rearrangement. This mechanistic pathway and HSAB considerations account for formation of both products and explain the three reported regiochemistry reversals, which are observed upon the introduction of (A) Lewis acid catalyst, (B) AcOH, or (C) solvent bulkiness.