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Synlett 2014; 25(07): 991-994
DOI: 10.1055/s-0033-1340954
DOI: 10.1055/s-0033-1340954
letter
MgCl2-Catalyzed α-Amination of α-Alkyl-β-ketoesters via Oxidative N-Acylnitroso Aldol Reaction with Hydroxamic Acids
Further Information
Publication History
Received: 22 January 2014
Accepted after revision: 17 February 2014
Publication Date:
17 March 2014 (online)
![](https://www.thieme-connect.de/media/synlett/201407/lookinside/thumbnails/10.1055-s-0033-1340954-1.jpg)
Abstract
A practical method for α-amination of α-alkyl-β-ketoesters using hydroxamic acids is described. In this protocol, an oxidative N-acylnitroso aldol reaction is catalyzed by magnesium chloride in the presence of the oxidant tert-butyl hydroperoxide.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
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References and Notes
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- 14 Less expensive T-HYDRO® (70 wt% tert-butylhydro-peroxide in water) can also be used as terminal oxidant in this reaction; it provides comparable yields to those reported in the text.
- 15 General Experimental Procedure for the MgCl2-Catalyzed α-Amination of α-Alkyl-β-ketoesters TBHP (5–6 M in decane, 0.48 mmol) was added dropwise to a mixture of β-ketoesters 1 (0.48 mmol), hydroxamic acids 2 (0.40 mmol), and MgCl2 (3.8 mg, 0.040 mmol) in MeCN (2 mL). The reaction was stirred at 40 °C for the indicated time; reaction completion was confirmed based on the disappearance of hydroxamic acids (Table 2). Then the reaction mixture was cooled to r.t., quenched with aq NaHSO3 solution and extracted with CH2Cl2 three times. The combined organic layers were dried over anhydrous Na2SO4, filtered, and then concentrated in vacuo. The residue was purified by column chromatography to afford amination product 3. This General Experimental Procedure was carried out using 1a (69.2 mg, 0.48 mmol) and 2a (53.2 mg, 0.40 mmol). The reaction mixture was stirred for 34 h at 40 °C and purified by silica gel chromatography using PE– CH2Cl2–EtOAc (4:1:0.75) as eluent to give product 3a (94.3 mg, 85%) as a colorless oil. The structure of 3a was identified by comparison of its 1H NMR and 13C NMR spectra with the reported data in ref. 8. See the Supporting Information for experimental details and characterization data for all new compounds.
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- 17 Chiral HPLC analysis conditions for 3a: Chiralcel AD-H column (0.46 cm × 25 cm), hexanes–i-PrOH (97:3), flow rate = 1.0 mL/min, λ = 210 nm, t R 1 = 16.4 min, t R 2 = 19.8 min.
For recent reviews, see:
For selected examples of nitrosoarenes serving as electrophilic sources of nitrogen or oxygen, see:
For O-selective acylnitroso aldol reactions, see:
For Rh2(cap)4-catalyzed oxidation of tertiary amines to initiate the Mannich reaction or [3+2] cycloaddition reaction, see:
For cascade transformations initiated by catalytic oxidation of tertiary amines using CuBr2 and TBHP, see:
For the use of magnesium halides as Lewis acids for the carbonyl-based enolization, see:
For selected examples of the use of (pybox)MgI2 catalysts in asymmetric catalysis involving β-dicarbonyl compounds, see: