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Synlett 2008(1): 129-133  
DOI: 10.1055/s-2007-1000835
LETTER
© Georg Thieme Verlag Stuttgart · New York

Unprecedented Intramolecular Nucleophilic Aromatic Additions of Allyloxy Anions to Diphenylphosphinoyl-Substituted Benzene Rings: A Facile Method for Preparing Multisubstituted Benzopyrans

Evugeni Gorobets, Masood Parvez, Brian A. Keay*
Department of Chemistry, University of Calgary, Calgary, AB, T2N 1N4, Canada
Fax: +1(403)2841372; e-Mail: keay@ucalgary.ca;
Further Information

Publication History

Received 2 October 2007
Publication Date:
11 December 2007 (online)

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Abstract

A new synthetic method for the preparation of multisubstituted benzopyrans that involves an intramolecular conjugate addition of allyloxy anions to diphenylphosphinoyl-substituted benzene rings is described. The intermediate anion is trapped with electrophiles providing benzopyrans that are readily oxidized with O2 to intermediates containing a peroxide that is easily converted into benzopyran-2-ones (i.e. coumarins).

Key words

nucleophilic aromatic additions - cyclizations - benzopyrans - coumarins

4

Interestingly, selection of a different proton source significantly improved both selectivity of the reaction and yield. For example, adding N-Boc-2-methylalanine methyl ester to anion 16 instead of H2O improved the isomeric ratio to 14:1:1.4 in favor of trans-11 and the yield from 48% to 85%.

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7-Benzyl-6-dimethoxymethyl-3-methyl-4 H -chromene (19a): To a solution of allylbenzene 1c (0.61 g, 1.45 mmol) in THF (15 mL) was added a solution LDA over 5 min (1.74 mmol) in THF (6 mL) at -78 °C. After 4 h at this temperature a solution of benzaldehyde (0.21 g, 2.0 mmol) in THF (3 mL) was added at -78 °C over 5 min upon which the dark cherry color disappeared. After 15 min of stirring at this temperature the reaction mixture was allowed to warm to r.t. for 1 h and quenched with aq sat. NH4Cl solution (5 mL) and H2O (5 mL) under stirring. After 10 min the organic phase was separated and the aqueous one was extracted with CH2Cl2 (2 × 40 mL). The combined organic extract was washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The residue was forwarded to silica gel column chromatography (35 g, hexanes-EtOAc-Et3N, 135:15:1) to give oily 19a (0.28 g, 62% yield). Please note 19a was easily oxidized to the corresponding peroxide (like 9) if left exposed to air. 1H NMR (200 MHz, C6D6): δ = 7.58 (s, 1 H, CH), 7.05-7.25 (m, 5 H, CH), 6.91 (s, 1 H, CH), 6.24 (q, J = 1.5 Hz, 1 H, CH), 5.50 [s, 1 H, CH(OMe)2], 4.10 (s, 2 H, Bn), 3.17 (s, 6 H, MeO), 3.05 (s, 2 H, CH2Ar), 1.32 (s, 3 H, Me). 13C NMR (50 MHz, C6D6): δ = 151.2 (C), 140.6 (C), 138.5 (C), 135.1 (CH), 130.7 (C), 128.9 (CH), 128.4 (CH), 128.3 (CH), 125.9 (CH), 118.3 (CH), 116.8 (C), 108.3 (C), 100.9 [CH(OMe)2], 52.0 (MeO), 37.7 (CH2), 28.3 (CH2), 17.5 (Me). IR (film): 3326, 2939, 2908, 2830, 1691, 1626, 1573, 1496, 1452, 1356, 1186, 1108, 1047, 987, 956, 735, 696 cm-1. MS (EI): m/z (rel. intensity) = 165 (11), 178 (14), 231 (11), 247 (100), 277 (11), 278 (100), 310 (38) [M+]. HRMS: m/z [M+] calcd for C20H22O3: 310.1569; found: 310.1546.

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The moderate yields of this reaction were due to the products being easily oxidized to their corresponding peroxides upon workup.

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The peroxides did not survive silica gel purification so they were used immediately in the next reaction. The peroxide was formed in 80-85% yield (by 1H NMR spectroscopy).