Metal-free oxidation of aromatic carbon-hydrogen bonds through a reverse-rebound mechanism
Yuan, C; Liang, Y; Hernandez, T; Berriochoa, A; Houk, KN; Siegel, D
HERO ID
2901000
Reference Type
Journal Article
Year
2013
Language
English
PMID
| HERO ID | 2901000 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | Metal-free oxidation of aromatic carbon-hydrogen bonds through a reverse-rebound mechanism |
| Authors | Yuan, C; Liang, Y; Hernandez, T; Berriochoa, A; Houk, KN; Siegel, D |
| Journal | Nature |
| Volume | 499 |
| Issue | 7457 |
| Page Numbers | 192-196 |
| Abstract | Methods for carbon-hydrogen (C-H) bond oxidation have a fundamental role in synthetic organic chemistry, providing functionality that is required in the final target molecule or facilitating subsequent chemical transformations. Several approaches to oxidizing aliphatic C-H bonds have been described, drastically simplifying the synthesis of complex molecules. However, the selective oxidation of aromatic C-H bonds under mild conditions, especially in the context of substituted arenes with diverse functional groups, remains a challenge. The direct hydroxylation of arenes was initially achieved through the use of strong Brønsted or Lewis acids to mediate electrophilic aromatic substitution reactions with super-stoichiometric equivalents of oxidants, significantly limiting the scope of the reaction. Because the products of these reactions are more reactive than the starting materials, over-oxidation is frequently a competitive process. Transition-metal-catalysed C-H oxidation of arenes with or without directing groups has been developed, improving on the acid-mediated process; however, precious metals are required. Here we demonstrate that phthaloyl peroxide functions as a selective oxidant for the transformation of arenes to phenols under mild conditions. Although the reaction proceeds through a radical mechanism, aromatic C-H bonds are selectively oxidized in preference to activated Csp3-H bonds. Notably, a wide array of functional groups are compatible with this reaction, and this method is therefore well suited for late-stage transformations of advanced synthetic intermediates. Quantum mechanical calculations indicate that this transformation proceeds through a novel addition-abstraction mechanism, a kind of 'reverse-rebound' mechanism as distinct from the common oxygen-rebound mechanism observed for metal-oxo oxidants. These calculations also identify the origins of the experimentally observed aryl selectivity. |
| Doi | 10.1038/nature12284 |
| Pmid | 23846658 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |