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DOI: 10.1055/a-1774-6966
Ceric Ammonium Nitrate Promoted Oxidative Coupling of Terminal Alkynes and 1,3-Keto Esters: A Synthesis of Unsymmetrical 1,1,2-Triacylalkenes
This research project was supported by the Thailand Research Fund (TRF; RSA6180045 for CT), the Thailand Science Research and Innovation (TSRI) for Chulabhorn Research Institute (Grant No. 313/2220) and for Chulabhorn Graduate Institute, Chulabhorn Royal Academy (FFB640035 Project Code 50171). It was also supported in part by a grant from Center of Excellence on Environmental Health and Toxicology (EHT), OPS, Ministry of Higher Education, Science, Research and Innovation. N.C. is grateful for support from the Royal Golden Jubilee (RGJ) scholarship program (PHD/0139/2560).
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Abstract
Unsymmetrical 1,1,2-triacylalkenes were conveniently prepared by the oxidative coupling of 1,3-keto esters with terminal alkynes by employing 4.0 equivalents of inexpensive ceric ammonium nitrate (CAN) as the oxidant in acetonitrile as the solvent at 0 °C. The method is milder than previously reported methods and can be conducted under air, thereby demonstrating its practicality and versatility for preparing these useful building blocks. The reaction is believed to occur by a single-electron-transfer process of the 1,3-keto ester substrate initiated by CAN to generate an α-radical species that quickly adds to the terminal alkyne partner in the reaction. Subsequent oxidation of the resulting vinyl radical by air and CAN then leads to the formation of the triacylalkene product as a mixture of E- and Z-isomers. The reaction was shown to be general, with 27 illustrative examples of the formation of the desired products in up to quantitative yield and with moderate to excellent alkene geometrical selectivities.
Key words
oxidative coupling - enediones - triacylalkenes - ceric ammonium nitrate - keto esters - alkynesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1774-6966.
- Supporting Information
Publication History
Received: 23 January 2022
Accepted after revision: 17 February 2022
Accepted Manuscript online:
17 February 2022
Article published online:
15 March 2022
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References and Notes
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- 9 Ethyl (2E)- and (2Z)-2-Benzoyl-4-oxo-4-phenylbut-2-enoates (3a); Typical Procedure CAN (1.266 g, 2.309 mmol, 4.0 equiv) was added in one portion to a solution of keto ester 1a (111.0 mg, 0.578 mmol, 1.0 equiv) and alkyne 2a (88.4 mg, 0.865 mmol, 1.5 equiv) in CH3CN (5.8 mL) at 0 °C, and the mixture was stirred 0 °C until the reaction was complete (TLC; typically 3–4 h). The mixture was then diluted with H2O, and the separated aqueous phase was extracted with EtOAc (×3). The combined organic phases were washed with sat. aq NaCl, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, 10% EtOAc –hexane) to give a thick yellow oil; yield: 157.1 mg (88%, E/Z = 74:26). IR (neat): 2983, 1723, 1666, 1449, 1220, 1008, 688 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.15 (s, 1 H), 7.97–7.89 [m, 4.06 H, (E+Z)], 7.63–7.54 [m, 2.28 H, (E+Z)], 7.50–7.43 [m, 4.39 H, (E+Z)], 7.25 [s, 0.05 H, (Z)], 4.28 (q, J = 7.2 Hz, 2 H), 4.13 [q, J = 7.2 Hz, 0.14 H, (Z)], 1.21 (t, J = 7.2 Hz, 3 H), 1.07 [t, J = 7.2 Hz, 0.24 H, (Z)]. 13C{1H} NMR (75 MHz, CDCl3): δ = 193.4, 188.4, 163.7, 144.9, 138.6, 136.2, 135.8, 134.2, 134.1, 133.8, 133.5, 133.4, 129.5, 128.88, 128.86, 128.8, 128.74, 128.66, 128.5, 62.4, 62.0, 13.9, 13.5. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H16NaO4: 331.0941; found: 331.0944.