Ceric Ammonium Nitrate Promoted Oxidative Coupling of Terminal Alkynes and 1,3-Keto Esters: A Synthesis of Unsymmetrical 1,1,2-Triacylalkenes

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 - alkynes

Publication History

Received: 23 January 2022

Accepted after revision: 17 February 2022

Accepted Manuscript online:
17 February 2022

Article published online:
15 March 2022

• References and Notes

• 1 Current address: Graduate School of Pharmaceutical Sciences, Chiba University, 1–8-1, Inohana, Chuo-ku, Chiba, 260–8675 Japan.
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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.