Synthesis of Highly Functionalized
Spirobenzofuranols and Spirobenzofuranones by Baylis-Hillman
Reaction

K. Karthikeyan; P. T. Perumal

doi:10.1055/s-0029-1217797

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Synlett 2009(14): 2366-2370
DOI: 10.1055/s-0029-1217797

LETTER

Synthesis of Highly Functionalized Spirobenzofuranols and Spirobenzofuranones by Baylis-Hillman Reaction

K. Karthikeyan, P. T. Perumal*
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600020, India
Fax: +91(44)24911589; e-Mail: ptperumal@gmail.com;

Further Information

Publication History

Received 25 May 2009
Publication Date:
06 August 2009 (online)

Abstract
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Abstract

Baylis-Hillman reaction of salicylaldehydes with N-aryl/alkyl maleimides under neat conditions for the synthesis of chromenes resulted in an unusual cyclization to form spirobenzofuranol derivatives in moderate to good yield. PDC oxidation of the resultant products yielded the corresponding spirobenzofuranone derivatives.

Key words

Baylis-Hillman reaction - salicylaldehyde - maleimide - DABCO - spirobenzofuranol - spirobenzofuranone

References and Notes

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14

Experimental Procedure for the Synthesis of Spiroben-zofuranol 3 and 4:
A mixture of salicylaldehyde 1 (1.62 mmol, 1.2 equiv),
N-substituted maleimide 2 (1.35 mmol, 1.0 equiv) and DABCO (30 mol%) was stirred at 70 ˚C under neat conditions for 1-2 h. The residue was dissolved in EtOAc (20 mL) and given a dilute HCl wash (1 × 20 mL) and H₂O wash (2 × 20 mL). The EtOAc layer was dried over anhyd Na₂SO₄ and removal of solvent under reduced pressure gave a crude product, which was purified by flash column chromatography with EtOAc-PE (20:80) as eluent to obtain spirobenzofuranols 3 and 4. Spectral Data of Compound 3b: colorless solid; mp 162-164 ˚C; R _f 0.33 (50% EtOAc-PE). IR: 3450, 2918, 1785, 1698, 1623, 1441, 1195 cm^-¹. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 1.26 (t, 3 H, J = 6.9 Hz), 2.85 (s, 3 H), 2.88 (d, 1 H, J = 18.3 Hz), 3.37 (d, 1 H, J = 18.3 Hz), 3.98-4.03 (m, 2 H), 5.19 (d, 1 H, J = 6.9 Hz), 6.17 (d, 1 H, J = 6.9 Hz), 6.87-6.95 (m, 3 H). ^¹³C NMR (125 MHz, DMSO-d ₆): δ = 15.1, 25.1, 35.0, 64.3, 73.8, 89.6, 114.5, 117.9, 122.6, 129.9, 143.7, 147.4, 174.3, 176.2. HRMS: m/z calcd for C₁₄H₁₅NO₅: 277.0952; found: 277.0957.

15

Crystallographic data of the compound 3a in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplemental publication no. CCDC-724171. Copies of the data can be obtained, free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or email: deposit@ccdc.cam.ac.uk].

17

Experimental Procedure for the Synthesis of Spiroben-zofuranone 9:
A mixture of salicylaldehyde 1 (1.62 mmol, 1.2 equiv),
N-substituted maleimide 2 (1.35 mmol, 1.0 equiv) and DABCO (30 mol%) was stirred under neat conditions at 70 ˚C for 1-2 h. After the formation of spirobenzofuranols 3 and 4, CH₂Cl₂ and PDC (1.2 equiv) were added to the reaction mixture and the mixture was refluxed. After 1 h the reaction mixture was filtered on a celite pad. The filtrate was concentrated, poured into H₂O, and extracted with EtOAc (3 × 20 mL). The organic layer was dried over anhyd Na₂SO₄ and removal of solvent under reduced pressure gave a crude product, which was purified by column chromatography with EtOAc-PE (10:90) as eluent to obtain the spirobenzofuranone 9. Spectral Data of Compound 9b: colorless solid; mp 136-138 ˚C; R _f 0.46 (40% EtOAc-PE). IR: 2930, 1715, 1602, 1383, 1159 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 1.47 (t, 3 H, J = 6.9 Hz), 3.06 (s, 3 H), 3.13 (d, 1 H, J = 18.4 Hz), 3.20 (d, 1 H, J = 17.6 Hz), 4.16 (q, 2 H, J = 6.9 Hz), 7.08 (t, 1 H, J = 7.6 Hz), 7.17 (d, 1 H, J = 8.4 Hz), 7.24 (t, 1 H, J = 7.6 Hz). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.8, 25.9, 37.4, 65.0, 86.9, 115.9, 120.4, 120.8, 124.2, 145.9, 163.1, 170.3, 172.5, 196.2. MS: m/z = 276 [M⁺ + 1]. Anal. Calcd for C₁₄H₁₃NO₅ (275.06): C, 61.09; H, 4.76; N, 5.09. Found: C, 61.17; H, 4.78; N, 5.01.