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Synlett 2002(4): 0580-0582
DOI: 10.1055/s-2002-22699
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Organocatalysts for the Asymmetric Catalytic Epoxidation of Alkenes Mediated by Chiral Iminium Salts

Philip C. Bulman Page*, Gerasimos A. Rassias, David Barros, Adel Ardakani, Donald Bethell, Eric Merifield
Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, England
e-Mail: p.c.b.page@lboro.ac.uk;
Further Information

Publication History

Received 5 February 2002
Publication Date:
05 February 2007 (online)

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Abstract

New iminium salt organocatalysts for catalytic asymmetric epoxidation based upon dibenzazepinium salts are reported, providing ee of up to ca 60%.

Key words

epoxidation - asymmetric - iminium salt - catalysis

1

Robert Robinson Laboratories, Department of Chemistry, University of Liverpool, Oxford Street, Liverpool L69 3BX, England.

2

AstraZeneca Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, England.

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5,7-Dihydrodibenzo[ c , e ]oxepine
A suspension of 2,2′-biphenyl dimethanol, (4.22 g, 19.5 mmol), in hydrobromic acid (60 mL, 24% in water), was heated to 100 °C for 40 min. The cloudy solution was allowed to cool and the aq phase extracted with diethyl ether (3 × 50 mL). The organic layers were washed with sat. aq sodium hydrogen carbonate (50 mL) and brine (50 mL) and dried over magnesium sulfate. The solvent was removed under reduced pressure to yield a colorless solid, which was recrystallized from ethyl acetate/light petroleum to give colorless crystals (3.25 g, 88%), mp 71-72 °C. Found: C, 85.57; H, 6.10. C14H12O requires C, 85.68; H, 6.17. νmax(film)/cm-1: 1567, 1197, 1073, 1042, 903, 891, 754, 602. 1H NMR (400 MHz, CDCl3): δ = 4.42 (4 H, s), 7.45-7.50 (4 H, m), 7.53-7.58 (2 H, m), 7.60-7.63 (2 H, m); 13C NMR (100 MHz, CDCl3): δ = 67.53, 127.46, 128.24, 128.91, 129.69, 135.16, 141.19; m/z = 196.0887; C14H12O [M+] requires 196.0888.
2-[2-(Bromoethyl)phenyl]benzene Carbaldehyde
To an ice-cooled solution of 5,7-dihydrodibenzo[c,e]oxe-pine (2.00 g, 10.2 mmol), in carbon tetrachloride (50 mL), in a round bottom flask equipped with a reflux condenser was added molecular bromine (1.76 g, 11.0 mmol), in carbon tetrachloride (6 mL), dropwise over 5 min (the reaction turned deep red). The cooling bath was removed and the reaction mixture heated under reflux until pale yellow and liberation of HBr ceased (ca 1 h). The solvent was removed under reduced pressure, diluted with diethyl ether (100 mL), washed with sat. aq sodium carbonate (2 × 50 mL) and brine (50 mL) and dried over magnesium sulfate. The solvents were removed under reduced pressure to yield a pale yellow oil, which was recrystallized from ethyl acetate/light petroleum to give a colorless solid (1.66 g, 59%), mp 56-58 °C; νmax(nujol)/cm-1: 1694, 1594, 1255, 1221, 1197, 761. 1H NMR (250 MHz, CDCl3): δ = 4.30 (2 H, dd, J = 27.1, 10.1 Hz), 7.22 (1 H, dd, J = 7.8, 1.6 Hz), 7.32-7.50 (3 H, m), 7.55 (2 H, dd, J = 6.1, 1.5 Hz), 7.66 (1 H, dd, J = 7.4, 1.6 Hz), 8.07 (1 H, dd, J = 8.2, 1.6 Hz), 9.74 (1 H, s); 13C NMR (100 MHz, CDCl3): δ = 33.83, 129.96, 130.88, 131.02, 131.40, 133.00, 133.05, 133.39, 135.95, 136.41, 138.28, 140.16, 145.63, 194.08; m/z = 275.9977; C14H11BrO [M+] requires 275.9974. General Procedure for the Synthesis of Dibenzo[ c , e ]aze-pinium Salts from 2-[2-(Bromoethyl)phenyl]benzene Carbaldehyde and Primary Amines A solution of the amine in ethanol, (10 mL per g of amine, 1 equiv), is added dropwise to a pre-cooled solution of 2-[2-(bromoethyl)phenyl]benzene carbaldehyde (1.10 equiv) in ethanol (10 mL per g) at 0 °C. The reaction mixture is stirred overnight while attaining ambient temperature. Sodium tetraphenylborate, (1.10 equiv), dissolved in the minimum amount of acetonitrile, is added in one portion and the reaction mixture stirred for 5 min. The solvents are removed under reduced pressure and ethanol is added to the residue, followed by water. The resulting solid is collected by filtration and washed with ethanol followed by diethyl ether.
(-)-2-[(4 S ,5 S )-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl]-5 H -dibenzo[ c , e ]azepinium Tetraphenylborate Prepared according to the general procedure from
(+)-(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-amine (3.85 g, 18.8 mmol). [12] The product was isolated as yellow plates (9.0 g, 68%), mp 187-188 °C(dec); [α]20 D -44.0 (c 1.01, CH3CN). Found: C, 85.23; H, 6.52; N, 1.96. C50H46BNO2 requires C, 85.34; H, 6.59; N, 1.99. νmax(film)/cm-1: 3055, 3038, 2999, 1633, 1579, 1480, 1451, 1385, 1203, 1114, 848, 735, 706. 1H NMR (400 MHz, DMSO-d6, 115 °C): δ = 1.71 (3 H, s), 1.74 (3 H, s), 4.32 (1 H, d, J = 21.8 Hz), 4.49 (1 H, d, J = 21.6 Hz), 4.68-4.77 (1 H, m), 4.72
(1 H, dd, J = 5.20, 21.8 Hz), 5.15 (1 H, d, J = 22.2 Hz), 5.82 (1 H, d, J = 4.1 Hz), 6.75 (4 H, t, J = 11.4 Hz), 6.88 (8 H, t, J = 11.5 Hz), 7.11-7.16 (5 H, m), 7.20-7.25 (8 H, m), 7.55-7.63 (3 H, m), 7.64-7.69 (3 H, m), 7.92-7.94 (2 H, m), 9.03 (1 H, s); 13C NMR (100 MHz, DMSO-d6, 120 °C): δ = 18.05, 28.41, 42.73, 60.81, 66.12, 70.48, 99.87, 120.42, 124.10, 124.16, 124.19, 124.39, 127.32, 127.59, 128.19, 129.00, 129.39, 132.58, 133.57, 134.95, 135.23, 140.48, 163.32, 171.11; m/z = 384.1968; C26H26NO2(cation) requires 384.1964.
(+)-6-[(1 R ,2 R ,3 R ,5 S )-2,6,6-Trimethylbicyclo[3.1.1]hept-3-yl]-5 H -dibenzo[ c , e ]azepinium Tetraphenylborate Prepared according to the general procedure from (-)-isopinocamphenylamine (3.12 g, 20.5 mmol). [13] The product was isolated as yellow plates (8.0 g, 60%), mp 212 °C (dec); [α]20 D +22.4 (c 1.00, CH3CN). Found: C, 87.81; H, 7.20; N, 1.95. C48H48BN·0.3 H2O requires C, 87.79; H, 7.37; N, 2.13. νmax(nujol)/cm-1: 1630, 1599, 1580, 1557, 1209, 756, 705, 612. 1H NMR (400 MHz, DMSO-d6, 80 °C): δ = 1.02 (3 H, d, J = 11.3 Hz), 1.14 (3 H, s), 1.35 (3 H, s), 1.48 (1 H, d, J = 16.8 Hz), 2.02 (1 H, td, J = 9.3, 2.6 Hz), 2.10-2.31 (2 H, m), 2.55-2.74 (3 H, m), 4.84-5.12 (3 H, m), 6.80 (4 H, t, J = 11.4 Hz), 6.93 (8 H, t, J = 11.8 Hz), 7.20-7.29 (8 H, m), 7.61-7.92 (6 H, m), 8.02 (1 H, td, J = 11.6, 2.2 Hz), 8.07-8.16 (1 H, m), 9.69 (1 H, s); 13C NMR (100 MHz, DMSO-d6, 80 °C): δ = 19.92, 23.76, 28.97, 33.69, 34.80, 40.00, 41.12, 42.15, 48.36, 53.99, 74.28, 122.23, 125.96, 127.77, 129.41, 129.65, 129.94, 130.31, 130.69, 131.08, 131.12, 135.41, 135.74, 136.55, 137.93, 141.90, 164.50, 171.15; m/z 330.2228; C24H28N(cation) requires 330.2222.
General Procedure for Catalytic Asymmetric Epoxidation of Unfunctionalized Alkenes Mediated by Iminium Salts To an ice-cooled solution of sodium carbonate (4 equiv), in water (12 mL per 1.20 g of sodium carbonate), OxoneΤ Μ (2 equiv) is added with stirring, and the resulting foaming solution is stirred for 5-10 min, until most of the effervescence subsides. The iminium salt (5 mol% with respect to the substrate) is added as a solution in acetonitrile (6 mL per 1.20 g of sodium carbonate used), followed by the alkene substrate (1 equiv), also as a solution in acetonitrile in the same volume as the solution of the catalyst. The suspension is stirred at 0 °C until the substrate is completely consumed (TLC analysis). The reaction mixture is diluted with ice-cooled diethyl ether (20 mL per 100 mg substrate) and this is immediately followed by the addition of the same volume of water. The aq phase is extracted four times with diethyl ether, the organic solutions are combined, washed with brine, and dried over magnesium sulfate. Filtration and evaporation of the solvents furnishes the product as a yellow or light brown residue which is purified by column chromatography, typically using ethyl acetate/light petroleum 1:99 to produce the pure epoxide.

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The IUPAC name for (-)-isopinocamphenylamine is (-)-6-(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-ylamine.