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Synlett 2008(1): 25-28  
DOI: 10.1055/s-2007-990921
LETTER
© Georg Thieme Verlag Stuttgart · New York

Intramolecular Ring-Opening Reactions of 1-(2-Methoxyphenyl)-6-oxabicyclo[3.2.0]heptanes: Spirocyclic Dihydrobenzofurans from Fused Bicyclic Oxetanes

Richard J. Boxalla, Richard S. Grainger*b, Caterina S. Aricòb, Leigh Ferrisc
a Department of Chemistry, King’s College London, Strand, London WC2R 2LS, UK
b School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Fax: +44(121)4144403; e-Mail: r.s.grainger@bham.ac.uk;
c AstraZeneca, Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, UK
Further Information

Publication History

Received 5 July 2007
Publication Date:
03 December 2007 (online)

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Abstract

Treatment of fused oxetanes with Et2AlCl, TMSCl, acetyl chloride, or ethereal hydrochloric acid leads to the formation of spirocyclic dihydrobenzofurans through intramolecular attack of an oxygen atom of a proximal phenolic methyl ether.

Key words

cyclizations - heterocycles - Lewis acids - neighboring-group effects - spiro compounds

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Typical Experimental for Oxetane Ring-Opening Reaction with HCl To a solution of oxetane 1a (50 mg, 0.18 mmol) in Et2O (5 mL) at 0 °C HCl (1 M in Et2O, 1.80 mL, 1.80 mmol) was added over a period of 10 min. The resulting solution was stirred for 18 h at r.t. The resulting mixture was poured into H2O (10 mL) and the aqueous layer was extracted with Et2O (2 × 10 mL). The combined organic phases were washed with brine (10 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified via column chromatography (hexane-EtOAc, 8:2) to furnish spirocycle 8a as a colorless oil (37 mg, 78%). R f = 0.2 (hexane-EtOAc, 8:2); mp 88-90 °C. IR (neat): νmax = 3445, 2945, 2865, 1651, 1497, 1466, 1199 cm-1. 1H NMR (360 MHz, CDCl3): δ = 6.65 (1 H, s, CCHCOCH3), 6.58 (1 H, s, CH2OCCHCCH3), 5.07 (1 H, dd, J = 6.8, 1.8 Hz, CHOH), 3.93 (1 H, d, J = 11.0 Hz, COCH2C), 3.79 (3 H, s, ArOCH3), 3.65 (1 H, d, J = 11.0 Hz, COCH2C), 2.19 (3 H, s, ArCH3), 2.16-2.11 (1 H, m, HOCHCH 2CH2), 1.97-1.94 (1 H, m, HOCHCH 2CH2), 1.61-1.50 (1 H, m, HOCHCH2CH 2), 1.49-1.44 (1 H, m, HOCHCH2CH 2), 1.26 (1 H, br, OH), 1.07 [3 H, s, C(CH3)2], 1.03 [3 H, s, C(CH3)2]. 13C NMR (100 MHz, CDCl3): δ = 17.0 (q), 24.6 (q), 26.7 (q), 32.2 (t), 40.9 (t), 44.9 (s), 56.9 (q), 64.9 (s), 65.2 (t), 92.8 (d), 108.6 (d), 111.7 (d), 125.3 (s), 128.2 (s), 152.1 (s), 156.1 (s). ESI-HRMS: m/z calcd for C16H22O3Na: 285.1461; found: 285.1457; LRMS (EI): m/z (%) = 262 (100) [M+], 231 (5), 205 (33), 192 (6), 175 (33), 163 (9).

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Typical Experimental Procedure for Oxetane Ring-Opening Reaction with AcCl To a solution of oxetane 1a (50 mg, 0.18 mmol) in DCE (10 mL) at r.t., AcCl (0.13 mL, 1.80 mmol) was added. The resulting solution was stirred overnight at r.t. poured into H2O (10 mL) and the aqueous layer was extracted with CH2Cl2 (2 × 10 mL). The combined organic phases were dried over MgSO4, filtered, and reduced in vacuo. The crude product was purified via column chromatography (hexane-EtOAc, 9:1) to furnish spirocycle 9a as a colorless oil (45 mg, 81%). R f = 0.2 (hexane-EtOAc, 9:1). IR (neat): νmax = 2950, 2869, 2252, 2105, 1739, 1651, 1490, 1464, 1223, 1047 cm-1. 1H NMR (360 MHz, CDCl3): δ = 6.66 (1 H, s, CCHCOCH3), 6.54 (1 H, s, CH2OCCHCCH3), 4.96 (1 H, dd, J = 6.8, 1.6 Hz, CHOCOCH3), 4.45 (1 H, d, J = 11.1 Hz, COCH2C), 4.16 (1 H, d, J = 11.2 Hz, COCH2C), 3.77 (3 H, s, ArOCH3), 2.18 (3 H, s, ArCH3), 2.15-2.12 (1 H, m, COCHCH 2CH2), 1.97 (3 H, s, OCOCH3), 1.99-1.91 (1 H, m, COCHCH 2CH2), 1.63-1.55 (1 H, m, COCHCH2CH 2), 1.52-1.48 (1 H, m, COCHCH2CH 2), 1.10 [3 H, s, C(CH3)2], 1.06 [3 H, s, C(CH3)2]. 13C NMR (125 MHz, CDCl3): δ = 16.5 (q), 20.9 (q), 24.6 (q), 26.4 (q), 31.9 (t), 39.6 (t), 44.9 (s), 56.4 (q), 61.7 (s), 67.1 (t), 92.3 (d), 109.0 (d), 111.2 (d), 125.9 (s), 127.3 (s), 151.4 (s), 154.8 (s), 171.0 (s). ESI-HRMS: m/z calcd for C18H24O4Na: 327.1567; found: 327.1562. LRMS (EI): m/z (%) = 304 (100) [M+], 262 (21), 175 (66), 160 (8), 115 (8), 91 (7), 69 (5), 43 (16).