Are β-Lactones Involved in Carbon-Based Olefination Reactions?

Abstract

Heteroatom-based olefinating reagents (e.g., organic phosphonates, sulfonates, etc.) are used to transform carbonyl compounds into alkenes, and their mechanism of action involves aldol-type addition, cyclization, and fragmentation of four-membered ring intermediates. We have developed an analogous process using ethyl 1,1,1,3,3,3-hexafluoroisopropyl methylmalonate, which converts electrophilic aryl aldehydes into α-methylcinnamates in up to 70% yield. The reaction plausibly proceeds through the formation of β-lactone that spontaneously decarboxylates under the reaction conditions. The results shed light on the Knoevenagel–Doebner olefination, for which decarboxylative anti-fragmentation of aldol-type adducts is usually considered.

Key words

olefination - carbonyl compounds - reaction mechanism - lactones - malonates - Knoevenagel–Doebner reaction

Publication History

Received: 19 December 2023

Accepted after revision: 14 February 2024

Accepted Manuscript online:
14 February 2024

Article published online:
02 April 2024

• References and Notes


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• 29 See the Supporting Information for details
• 30 α-Methylcinnamates 12a–m; General Procedure A 30 mL Schlenk flask was charged with diester 5b (2.2 mmol) and the appropriate aldehyde (2.0 mmol), and the mixture was purged with argon. Anhyd THF (8 mL) was added, followed by dropwise addition of DBU (0.6 mL; 4.0 mmol) over ~90 s with stirring. The flask was then immersed in an oil bath at 40 °C for 16 h. The mixture was cooled to rt, poured into 5% aq NaHCO₃ (50 mL), and extracted with EtOAc (3 × 50 mL). The combined organic phases were washed with H₂O (50 mL) and brine (50 mL), then dried (MgSO₄), filtered, and concentrated. The residue was purified by column chromatography [silica gel (d = 20 cm; ø = 3 cm)]. Ethyl (2E)-2-Methyl-3-phenylacrylate (12a) Eluent: cyclohexane–toluene (2:1). Colorless oil; yield: 91 mg (0.48 mmol, 23%). ¹H NMR (400 MHz, CDCl₃): δ = 7.67 (d, J = 1.5 Hz, 1 H), 7.42–7.26 (m, 5 H), 4.26 (q, J = 7.1 Hz, 2 H), 2.10 (d, J = 1.5 Hz, 3 H), 1.34 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.7, 138.6, 136.0, 129.6, 128.6, 128.3, 128.2, 60.8, 14.3, 14.0. The NMR spectra were consistent with those reported in the literature.³³ Ethyl (2E)-3-(2-Bromophenyl)-2-methylacrylate (12b) Eluent: cyclohexane–toluene (2:1). Colorless oil; yield: 170 mg (0.64 mmol, 32%). ¹H NMR (400 MHz, CDCl₃): δ = 7.69–7.66 (m, 1 H), 7.57 (dd, J = 8.0, 1.1 Hz, 1 H), 7.32–7.23 (m, 2 H), 7.17–7.10 (m, 1 H), 4.26 (q, J = 7.1 Hz, 2 H), 1.94 (d, J = 1.6 Hz, 3 H), 1.32 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.9, 137.9, 136.2, 132.6, 130.4, 130.3, 129.4, 126.9, 124.1, 60.9, 14.2, 13.9. The NMR spectra were consistent with those reported in the literature.³³
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• 32 Distinction between open-chain aldol-type adduct and cyclized β-lactone is difficult, when analyzing mixture of components with NMR spectroscopy. Therefore, we remain cautious with definite statements, concerning the structure of intermediate I.
• 33 Leung PS.-W, Teng Y, Toy PH. Org. Lett. 2010; 12: 4996
• 34 For a biosynthesis of olefinic hydrocarbons via β-lactones, see: Christenson, J. K.; Richman, J. E.; Jensen, M. R.; Neufeld, J. Y.; Wilmot, C. M.; Wackett, L. P. Biochemistry 2017, 56, 348; and references cited therein.