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Synlett 2009(13): 2079-2082  
DOI: 10.1055/s-0029-1217563
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Novel 3-Bromo-2H-chromene Derivatives: Palladium-Mediated Intramolecular Cyclization of Aryl Propargyl Ethers

Gurunathan Savitha, Kulandhai Felix, Paramasivan T. Perumal*
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
Fax: +91(44)24911589; e-Mail: ptperumal@gmail.com;
Further Information

Publication History

Received 31 March 2009
Publication Date:
15 July 2009 (online)

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Abstract

Aryl propargyl ethers were cyclized in the presence of catalytic amount of Pd(OAc)2 in conjunction with stoichiometric amount of CuBr2 and LiBr to the corresponding 3-bromo-2H-chromene derivatives in good yields. The protocol was further extended to synthesize 3-bromo-benzofused 2H-chromene derivatives.

Key words

palladium-mediated cyclization - 3-bromo-2H-chromenes - aryl propargyl ethers - LiBr - CuBr2

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15

General Procedure for the Synthesis of 3-Bromo-2 H -chromene Derivatives 2a-l To a stirred mixture of the aryl propargyl ether 1a-l (1 mmol) in AcOH, Pd(OAc)2 (5 mol%), LiBr (1 mmol), and CuBr2 (2.5 mmol) were added at r.t. The reaction mixture was stirred until completion of the reaction as monitored by TLC. A sat. solution of NaHCO3 was then added to neutralize the reaction mixture, which was then extracted with EtOAc (3 × 10 mL). The organic layer was dried over anhyd Na2SO4. Removal of the solvent under reduced pressure gave the crude product, which was purified by column chromatography on silica gel using hexane as eluent to afford the pure product.

16

3-Bromo-4-ethyl-2 H -chromene (2a, Table 1, Entry 1)
Colorless oily liquid. IR (KBr): νmax = 3062, 2966, 2851, 2354, 1629, 1467 cm-¹.¹H NMR (500 MHz, CDCl3): δ = 1.14 (t, 3 H, J = 7.5 Hz), 2.65 (q, 2 H, J = 7.5 Hz), 4.86 (s, 2 H), 6.86 (d, 1 H, J = 8.0 Hz), 6.95 (t, 1 H, J = 7.5 Hz), 7.16 (t, 1 H, J = 7.5 Hz), 7.22 (d, 1 H, J = 8.0 Hz). ¹³C NMR (125 MHz, CDCl3): δ = 12.4, 23.8, 70.8, 112.9, 116.3, 121.9, 122.6, 123.6, 129.1, 134.6, 153.3. ESI-MS: m/z = 239 [M+ + 1], 241 [M+ + 3]. Anal. Calcd (%) for C11H11BrO: C, 55.26; H, 4.65. Found: C, 55.31; H, 4.71.

17

3-Bromo-4-ethyl-2 H -benzo[ h ]chromene (2f, Table 2, Entry 1)
Colorless oily liquid. IR (KBr): νmax = 3062, 2956, 1738, 1642, 1561, 1466 cm-¹.¹H NMR (500 MHz, CDCl3): δ = 1.96 (t, 3 H, J = 7.7 Hz), 2.75 (q, 2 H, J = 7.7 Hz), 5.06 (s, 2 H), 7.38 (d, 1 H, J = 8.2 Hz), 7.45-7.49 (m, 3 H), 7.76-7.8 (m, 1 H), 8.17-8.19 (m, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 12.6, 24.1, 71.3, 110.7, 117.3, 121.2, 121.4, 122.2, 124.6, 125.9, 126.8, 127.6, 134.0, 135.3, 149.1. ESI-MS: m/z = 289 [M+ + 1], 291 [M+ + 3]. Anal. Calcd (%) for C15H13BrO: C, 62.30; H, 4.53. Found: C, 62.21; H, 4.65.