Baylis–Hillman Adducts as a Valuable Source for Synthesis of Functionalized [4,4,4]-Propellone Dilactone Derivatives

Payal Malvi; Dharti Mistry; Galla V. Karunakar; Diksha Rajput; Dandamudi V. Lenin

doi:10.1055/a-2517-2139

Synlett, Table of Contents

Synlett 2025; 36(15): 2376-2380
DOI: 10.1055/a-2517-2139

letter

Emerging Trends in Organic Chemistry: A Focus on India

Baylis–Hillman Adducts as a Valuable Source for Synthesis of Functionalized [4,4,4]-Propellone Dilactone Derivatives

Authors

Payal Malvi

^aSchool of Chemical Sciences, Central University of Gujarat, Sector-30, Gandhinagar-382030, India
Dharti Mistry

^aSchool of Chemical Sciences, Central University of Gujarat, Sector-30, Gandhinagar-382030, India
Galla V. Karunakar

^bCSIR-Indian Institute of Chemical Technology [CSIR-IICT], Hyderabad-500076, India
Diksha Rajput

^cDepartment of Chemistry, IIT Gandhinagar, Gandhinagar-382355, India
Dandamudi V. Lenin ∗

^aSchool of Chemical Sciences, Central University of Gujarat, Sector-30, Gandhinagar-382030, India

Abstract

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Abstract

A simple and facile synthesis of functionalized [4,4,4]-propellone dilactone derivatives through dialkylation of cyclic 1,3-diketones with Baylis–Hillman adducts and subsequent dilactonization is described. This methodology is appealing because it is reliable and scalable (the products can be synthesized on a gram scale). The tricyclic products can be exploited for their biological activity.

Key words

Baylis–Hillman adducts - propellones - cyclic diketones - alkylation - lactonization

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References

References and Notes

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11 CCDC 2236868 and CCDC: 2235335 contain the supplementary crystallographic data for compounds 4a and 4l, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
12 Di-tert-butyl (2E,2′E)-2,2′-[(2,6-Dioxocyclohexane-1,1-diyl)di(methylene)]bis(3-phenylacrylate) (3a); Typical Procedure Oil-free NaH (10 mmol, 0.24 g) was added to a stirred solution of cyclohexane-1,3-dione (2a; 2mmol, 0.234 g) in anhyd toluene, and the mixture was refluxed for 1 h under N₂. tert-Butyl 3-acetoxy-2-methylene-3-phenylpropanoate (5 mmol, 1.38g) was then added and the mixture was stirred and refluxed for 30 h until the reaction was complete (TLC). The reaction was then quenched 1% aq AcOH (50 mL), and the organic layer was extracted with Et₂O (3 × 25 mL). The combined organic layer was washed with H₂O (20 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 8% EtOAc–hexanes) to give a colorless solid; yield: 72%; mp 83–90 °C. IR (ATR): l _max: 2976, 1693, 1722, 1156, 780 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.37 (s, 2 H), 7.20 (m, 6 H), 7.06–7.10 (m, 4 H), 2.77 (s, 4 H), 2.63 (t, J = 6.7 Hz, 4 H), 2.08 (m, 2 H), 1.39 (s, 18 H). ¹³C NMR (125 MHz, CDCl₃): δ = 208.88, 167.81, 140.20, 135.78, 130.11, 129.11, 128.35, 127.87, 81.09, 66.23, 37.74, 31.35, 28.10, 17.62. HRMS (ESI): m/z [M + H]⁺ calcd C₃₄H₄₁O₆: 545.2898; found: 545.2899. (4E,8E)-4,8-Dibenzylidene-2,10-dioxatricyclo[4.4.4.0^1,6]tetradecane-3,9,14-trione (4a); Typical Procedure TFA (5mmol, 0.57 g) was added to a stirred solution of 3a (1 mmol, 0.54 g) in DCE (5 mL) and the mixture was stirred at r.t. for 15 min. TFAA (2.5 mmol, 0.52 g) was then added and the mixture was refluxed for 3 h until the reaction was complete (TLC). The solvent was removed under reduced pressure and the residue was diluted with H₂O (20 mL) and extracted with Et₂O (3 × 25 mL). The combined organic layer was washed with sat. aq NaHCO₃ (20 mL) and then dried (Na₂SO₄) and concentrated. The crude product was dissolved in Et₂O (5 mL) precipitated by addition of pentane. The precipitate was collected by filtration and dried in a high vacuum to give an off-white solid; yield: 65%; mp 214–218 °C. IR (ATR): l _max: 2934, 1728, 1274, 985, 833 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.97 (s, 2 H), 7.34–7.40 (m, 10 H), 3.38 (dd, J = 17.1, 2.2 Hz, 2 H), 2.66 (d, J = 2.3 Hz, 1 H), 2.58–2.64 (m, 3 H), 2.30 (dd, J = 7.2, 5.4 Hz, 2 H), 1.97–2.04 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 205.89, 163.36, 145.55, 134.13, 130.61, 130.25, 128.96, 119.54, 105.75, 49.71, 35.10, 32.74, 29.92, 18.43. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₂₃O₅: 415.1540; found: 415.1535.

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