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Synlett 2009(14): 2366-2370  
DOI: 10.1055/s-0029-1217797
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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;
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Publication History

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

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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

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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.

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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].

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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.