Copper-Catalyzed Cross-Dehydrogenative Coupling of α-Hydroxy Esters with Nitromethane

Abstract

An efficient copper-catalyzed tandem oxidation/nitroaldol reaction of hydroxyl compounds with nucleophiles is developed. In this work, β-nitro-α-hydroxy esters were prepared via cross-dehydrogenative coupling reaction using α-hydroxy esters as hydroxy compounds and nitromethane as a nucleophile. The reaction is believed to undergo an oxidation of the hydroxy group and then an addition of the generated carbonyl group. It is an example of CDC reactions related to hydroxy compounds via carbonyl intermediates.

Key words

alcohols - copper - cross-coupling - dehydrogenation - nucleophilic addition

Publication History

Received: 29 May 2021

Accepted after revision: 29 June 2021

Accepted Manuscript online:
29 June 2021

Article published online:
23 July 2021

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• 12 Methyl 2-Hydroxy-3-nitro-2-phenylpropanoate (2a): Typical Procedure Methyl 2-hydroxy-2-phenylacetate (166.2 mg, 1.0 mmol, 1.0 equiv.), NaHCO₃ (84.0 mg, 1.0 mmol, 1.0 equiv.), nitromethane (1.0 mL), aqueous tert-butyl hydroperoxide (70% solution in water, 321.9 mg, 2.5 mmol, 2.5 equiv.), and CuO (15.9 mg, 0.2 mmol, 0.2 equiv.) were added to a flask successively. Then the mixture was heated to 80 °C and stirred for 5 h. After that, the mixture was cooled to room temperature. Afterwards 10.0 mL of ethyl acetate and 10 mL of Na₂S₂O₃ aqueous solution (0.5 mol/L) were added to the flask, and the organic layer was washed with brine, dried over anhydrous Na₂SO₄, filtered, concentrated, and purified by flash column chromatography with silica gel (200–300 mesh) using petroleum ether/ethyl acetate (8:1) to give a light yellow solid; yield 136.4 mg (61%), mp 85–86 °C. ¹H NMR (600 MHz, CDCl₃): δ = 7.75 (d, J = 8.4 Hz, 2 H), 7.30 (d, J = 8.4 Hz, 2 H), 7.28–7.23 (m, 3 H), 7.22–7.16 (m, 2 H), 4.93–4.80 (m, 1 H), 4.11 (d, J = 6.6 Hz, 2 H), 2.44 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 143.6, 136.9, 136.4, 129.9, 128.8, 128.0, 127.3, 47.4, 21.7. HRMS (ESI): m/z [M – H]^– calcd for C₁₀H₁₀NO₅: 224.0559; found: 224.0558.