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Synlett 2008(16): 2500-2502  
DOI: 10.1055/s-2008-1078057
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Approach to Benzannelated [5,6]-Spiroketals

Christopher D. Bray
School of Biological and Chemical Sciences, The Walter Besant Building, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
Fax: +44(20)78827427; e-Mail: c.bray@qmul.ac.uk;
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Publication History

Received 9 May 2008
Publication Date:
12 September 2008 (online)

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Abstract

Heating a variety of 2-hydroxybenzyl acetates bearing a range functional groups on the 4- or 5-position of the aromatic ring at 100 ˚C in neat γ-methylene-γ-butyrolactone (1.0 M) for 20 hours gives a series of benzannelated [5,6]-spiroketals in 75-89% yield.

Key words

Diels-Alder reactions - spiro compounds - heterocycles - natural products - ortho-quinone methide

    References and Notes

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10

General Procedure: 2-Hydroxybenzyl acetate (8a; 40 mg, 0.24 mmol) in γ-methylene-γ-butyrolactone (0.24 mL,
1.0 M) was heated at 100 ˚C for 20 h. The cooled reaction mixture was purified by flash column chromatography (SiO2, 25% → 30% EtOAc in PE) to give 9a as a white solid (36 mg, 84%); mp 107-108 ºC (lit.¹² 106 ºC); R f 0.26 (EtOAc-PE, 3:7). IR: 2961, 2920, 1776 (C=O), 1582, 1489, 1447, 1251, 1220, 1170, 1093, 1055 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.07-7.17 (m, 2 H, 2 × ArCH), 6.93 (dt, J = 7.4, 1.1 Hz, 1 H, ArCH), 6.81 (dd, J = 8.1, 1.1 Hz, 1 H, ArCH), 3.06-3.18 (m, 1 H, 1 H of CH2), 2.91-3.04 (m, 1 H, 1 H of CH2), 2.79 (ddd, J = 16.5, 6.0, 2.5 Hz, 1 H, 1 H of CH2), 2.64 (ddd, J = 17.6, 9.5, 2.5 Hz, 1 H, 1 H of CH2), 2.52 (ddd, J = 13.1, 9.5, 2.5 Hz, 1 H, 1 H of CH2), 2.19-2.35 (m, 2 H, 2 × 1 H of CH2), 2.06-2.16 (m, 1 H, 1 H of CH2). ¹³C NMR (100 MHz, CDCl3): δ = 175.5 (C=O), 151.4 (ArCO), 129.0 (ArCH), 127.5 (ArCH), 121.6 (ArCH), 120.9 (ArC), 116.7 (ArCH), 106.2 (OCO), 33.8 (CH2), 30.1 (CH2), 28.2 (CH2), 21.4 (CH2). HRMS (EI): m/z [M + Na]+ calcd for C12H12O3Na: 227.0684; found: 227.0690.