Premium
Regiochemical Reversals in Nitrosobenzene Reactions with Carbonyl Compounds – α‐Aminooxy Ketone versus α‐Hydroxyamino Ketone Products
Author(s) -
Nelson Donna J.,
Kumar Ravi
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200893
Subject(s) - chemistry , regioselectivity , ketone , hsab theory , nucleophile , nitrosobenzene , lewis acids and bases , allylic rearrangement , pericyclic reaction , steric effects , medicinal chemistry , stereochemistry , catalysis , organic chemistry
The Lewis acid catalyzed reaction of nitrosobenzene with a ketone can produce an α‐aminooxy ketone or an α‐hydroxyamino ketone; the reaction regiochemistry switches from the latter to the former upon the addition of a Lewis acid or sterically‐hindered solvent. Whereas the latter (C–N bond formation) is easily explained by attack of the enolate α‐carbon at the N atom, the former (C–O bond formation) has been an enigma, with few proposed explanations, and none that explains the simultaneous formation of both products and all the regiochemical reversals. Herein, the regiochemistry reversal is proposed to occur by (1) nucleophile formation governed by hard and soft acids and bases (HSAB) theory, (2) a nucleophilic attack by the enolate O atom at the N atom, followed by (3) a [2,3]‐sigmatropic rearrangement. This mechanistic pathway and HSAB considerations account for the 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.