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Synlett 2006(5): 0745-0746  
DOI: 10.1055/s-2006-933111
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Multiply ortho-Substituted Diaryl Ethers via Lithiation and Oxidation of a Dibenzosiloxane (Phenoxasilin)

Mark S. Betson, Jonathan Clayden*
School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Fax: +44(161)2754939; e-Mail: clayden@man.ac.uk;
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Publication History

Received 8 November 2005
Publication Date:
09 March 2006 (online)

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Abstract

Lithiation of dibenzosiloxanes (phenoxasilins or 9-sila­xanthenes), followed by oxidation of the C-Si bonds, provides a versatile method for the synthesis of 2,6,2′,6′-tetrasubstituted diaryl (biaryl) ethers.

Key words

diaryl ether - synthesis - lithiation - ipso electrophilic aromatic substitution

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3,6,10,10-Tetramethyl-9-silaxanthene ( 3) p-Tolyl ether (5.0 g, 25.2 mmol) was dissolved in dry TMEDA (50 mL) and cooled to 0 °C under a nitrogen atmosphere. n-BuLi (2.5 M solution in hexane, 30.3 mL, 75.7 mmol) was added and the mixture stirred for 20 min at 0 °C. The ice bath was removed and the mixture was stirred for 12 h, after which time the solution had turned dark orange. The mixture was cooled to 0 °C and dimethyl-dichlorosilane (4.60 mL, 37.9 mmol) added dropwise which resulted in an exothermic reaction. The mixture was stirred for a further 2 h at 0 °C and sat. aq NH4Cl solution (50 mL) added, followed by EtOAc (50 mL). The layers were separated and the aqueous layer washed with EtOAc (3 × 30 mL) and the combined organic fractions were washed with aq HCl (3 M, 30 mL), H2O (30 mL), brine (30 mL), dried (MgSO4) and solvents removed. The residue was purified by flash chromatography (silica, PE) to give the dibenzo-siloxane 3 as a viscous colorless oil (2.47 g, 9.71 mmol, 40%) which crystallized on standing (plates, mp 47-49.5 °C); R f = 0.50 (PE). IR (film): νmax = 2952 (CH), 2919 (CH), 1458 (aromatic) cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.40-7.36 (2 H, m, SiCCH), 7.32-7.26 (2 H, m, MeCCH), 7.16 (2 H, d, J = 8.4 Hz, OCCH), 2.46 (6 H, s, PhMe), 0.54 (6 H, s, SiMe2). 13C NMR (75 MHz, CDCl3): δ = 158.0, 134.1, 132.2, 131.7, 119.0, 118.0, 21.0, -0.0. MS (EI): m/z (%) = 254 (50) [M], 239 (100) [M - CH3]. HRMS: m/z calcd for C16H18OSi: 254.1121; found: 254.1129.

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3,6,8,10,10-Pentamethyl-9-silaxanthene ( 7a) The dibenzosiloxane 3 (500 mg, 1.965 mmol) was dissolved in dry Et2O (10 mL) and dry TMEDA (0.44 mL, 2.95 mmol) and cooled to -78 °C under a nitrogen atmosphere. s-BuLi (1.1 M solution in cyclohexane, 2.68 mL, 2.95 mmol) was added and after 10 min the dry ice bath was replaced with an ice bath. The orange solution was stirred for 2 h and MeI (0.18 mL, 2.95 mmol) was added. The mixture was stirred for 14 h with gradual warming to r.t. Then, sat. aq NH4Cl solution (5 mL) was added and the layers separated. The aqueous layer was washed with Et2O (3 × 5 mL) and the combined organic fractions were washed with H2O (2 × 5 mL), brine (5 mL), dried (MgSO4) and solvents removed under reduced pressure. The residue was purified by flash chromatography (silica, PE) to give the dibenzosiloxane 7a as a colorless oil (400 mg, 1.49 mmol, 76%); R f = 0.67 (PE). IR (film): νmax = 2951 (CH), 2920 (CH), 1604 (aromatic), 1586 (aromatic) cm-1. 1H NMR (300 MHz; CDCl3): δ = 7.39 (2 H, s, ArH), 7.32-7.14 (4 H, m, 4 × ArH), 2.50 (3 H, s, ArMe A), 2.45 (3 H, s, ArMe B), 2.42 (3 H, s, ArMe C), 0.54 (6 H, s, SiMe2). 13C NMR (75 MHz, CDCl3): δ = 158.2, 156.2 (O-C), 134.0, 133.6, 132.1, 131.7, 131.5, 126.9, 126.7, 119.2, 118.6, 118.0 (aromatics), 21.0, 20.9, 17.2 (ArMe), -0.06 (SiMe2). MS (EI): m/z (%) = 268 (50) [M+], 253 (100) [M - Me]. HRMS: m/z calcd for C17H20OSi: 286.1622; found: 286.1622.

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2,2′-Diiodo-4,4′,6-Trimethylbiphenyl Ether ( 8) The dibenzosiloxane 7a (890 mg, 3.317 mmol) was dissolved in dry CH2Cl2 (20 mL) under a nitrogen atmosphere and cooled to 0 °C. Iodine monochloride (1.0 M in CH2Cl2, 6.97 mL, 6.97 mmol) was added and the mixture stirred for 30 min after which time the ice bath was removed. And stirred for a further 12 h. Then, sat. aq Na2S2O3 solution (25 mL) was added and the layers separated. The aqueous layer was washed with CH2Cl2 (3 × 25 mL) and the combined organic fractions were washed with H2O (2 × 25 mL), brine (25 mL), dried (MgSO4) and solvents removed. The residue was purified by flash chromatography (silica, PE) to give the ether 8 (859 mg, 1.85 mmol, 55%) as a crystalline solid (plates), mp 122.5-124.2 °C (hexane-EtOAc). R f = 0.55 (PE). IR (film): νmax = 3019 (CH), 2919 (CH), 1602 (aromatic), 1481 (aromatic) cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.74 [1 H, d, J = 2.0 Hz, (ICCH)A], 7.58 (1 H, s, (ICCH)B], 7.08 (1 H, s, MeCCHCMe), 6.98 (1 H, dd, J = 8.5, 2.0 Hz, OCCHCH), 6.20 (1 H, d, J = 8.5 Hz, OCCH), 2.36 (3 H, s, ArMeA), 2.31 (3 H, s, ArMeB), 2.16 (3 H, s, ArMeC). 13C NMR (75 MHz, CDCl3): δ = 153.8, 151.1, 140.5, 138.3, 138.0, 137.3, 133.4, 132.7, 133.4, 132.7, 132.6, 130.1, 113.1, 92.0 (C-I), 85.4 (C-I), 20.7, 20.4, 17.6. MS (EI): m/z (%) = 464 (15) [MH+], 210 (100) [M - I2]. HRMS: m/z calcd for C15H14OI2: 463.9129; found: 463.9127.

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Betson, M. S.; Clayden, J.; Worrall, C. P.; Peace, S., manuscript in preparation.