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Synlett 2018; 29(17): 2298-2300
DOI: 10.1055/s-0037-1610292
DOI: 10.1055/s-0037-1610292
letter
Brønsted Acid Mediated Direct α-Hydroxylation of Cyclic α-Branched Ketones
This work was partially supported by Max Planck Society and the DFGFurther Information
Publication History
Received: 21 August 2018
Accepted after revision: 02 September 2018
Publication Date:
26 September 2018 (online)
![](https://www.thieme-connect.de/media/synlett/201817/lookinside/thumbnails/st-2018-d0535-l_10-1055_s-0037-1610292-1.jpg)
Abstract
We report a Brønsted acid mediated direct α-hydroxylation of cyclic α-branched ketones via a tandem aminoxylation/N–O bond-cleavage process. Nitrosobenzene is used as the oxidant and subsequently promotes the liberation of the free alcohol. The desired products could be isolated in moderate to good yields at a maximum tested scale of 10 mmol. Derivatizations of the obtained products are presented.
Key words
α-branched ketones - α-hydroxylation - aminoxylation - α-functionalization of ketones - enolization - Brønsted acid mediatedSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610292.
- Supporting Information
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- 10 Exemplary Procedure In a GC vial 2-phenylcyclohexanone (1a, 43.6 mg, 0.25 mmol, 1.0 equiv) was dissolved in a solution of trichloroacetic acid (0.75 mmol, 3.0 equiv) in dry PhMe (2.5 mL) and nitrosobenzene (0.625 mmol, 2.5 equiv) was added. The vial was closed with a screw cap, and the resulting mixture was stirred at r.t. for 16 h. The crude reaction mixture was directly purified by flash column chromatography (SiO2, hexanes/EtOAc = 100:0 then 10:1) to give 2-hydroxy-2-phenylcyclohexan-1-one (2a) as an orange oil (28.7 mg, 60%). 1H NMR (500 MHz, CDCl3): δ = 7.42–7.27 (m, 2 H), 7.35–7.29 (m, 3 H), 5.04 (sbr, 1 H), 3.06–2.99 (m, 1 H), 2.59–2.51 (m, 1 H), 2.48–2.39 (m, 1 H), 2.11–2.02 (m, 1 H), 1.91–1.83 (m, 2 H), 1.82–1.68 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 212.9, 139.8, 129.3, 128.6, 126.5, 80.3, 39.0, 38.9, 28.5, 23.2. HRMS (ESI+): m/z calcd for C12H14O2Na [M + Na]+: 213.0886; found: 213.0885.
For commonly applied methods, see:
For selected publications regarding the direct α-hydroxylation of α-branched ketones, see:
For selected reviews on organocatalytic aminoxylations, see:
For publications regarding enol catalysis by our group, see:
For independent contributions from other groups, see:
For an account on heterodimeric activation in organocatalysis, see: