Expedient Synthesis of Highly Functionalized Coumarin Derivatives through a Domino Reaction

Abstract

The straightforward synthesis of novel pentacyclic and hexacyclic coumarin heterocycles in a one-pot domino reaction is described. The process enables the synthesis of diversified coumarins in high yields in a single step.

Key words

domino reaction - Knoevenagal condensation - hetero- Diels-Alder reaction - Baylis-Hillman adducts

References and Notes

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16

Synthesis of Polycyclic Coumarin Derivative 3a - Typical Procedure
To a refluxing solution of coumarin 2 (1 mmol) in anhyd DMF (5 mL), aldehyde 1a (1mmol), piperidine (5 mol%) were added, and the reaction mixture was refluxed for 4-5 h until the disappearance of starting material as evidenced by TLC. After completion of the reaction, H₂O (5 mL) was added, and the reaction mixture was extracted with EtOAc
(3 × 15 mL), dried (Na₂SO₄), and the solvent was evaporated. The residue was subjected to column chromatography using hexane-EtOAc (95:5).
Compound 3a: R _f = 0.5; white solid, mp 112-114 ˚C. IR (KBr): 1635 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.52 (s, 3 H), 4.35 (d, J = 11.4 Hz, 1 H), 4.57 (d, J = 11.4 Hz, 1 H), 4.86 (s, 1 H), 5.62 (s, 1 H), 6.58-7.85 (m, 13 H). ^¹³ NMR (75 MHz, CDCl₃): δ = 36.68, 48.60, 52.85, 61.91, 81.89, 104.21, 114.81, 116.00, 116.47, 117.79, 120.00, 122.87, 123.92, 126.59, 127.90, 128.42, 128.97, 129.23, 132.24, 134.00, 134.47, 152.47, 152.94, 158.50, 161.15, 170.56. HRMS (EI): m/z = 441.1330 [M⁺].

17

Crystallographic data of compound 3f in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplemental publication no. CCDC-768492. Copies of the data can be obtained, free of charge on application to CCDC, 12 Union Road, Cambridge CB2 IEZ, UK [fax: [phone] or email: [e-mail]].