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Synlett 2005(9): 1413-1416  
DOI: 10.1055/s-2005-868515
LETTER
© Georg Thieme Verlag Stuttgart · New York

Extending the Scope of the [2+2] Cycloaddition of Dichloroketene to Chiral Enol Ethers: Synthesis of (-)-Detoxinine

Julien Ceccon, Jean-François Poisson*, Andrew E. Greene
Université Joseph Fourier de Grenoble, Chimie Recherche (LEDSS), 38041 Grenoble, France
Fax: +33(4)76514494; e-Mail: jean-francois.poisson@ujf-grenoble.fr;
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Publikationsverlauf

Received 25 March 2005
Publikationsdatum:
29. April 2005 (online)

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Abstract

Allylic oxidation of a known lactam, obtained by asymmetric [2+2] cycloaddition of dichloroketene to a chiral enol ether, followed by Beckmann ring expansion and dechlorination, affords a potential intermediate for the synthesis of various natural products. The usefulness of this intermediate is first demonstrated by an asymmetric synthesis of (-)-detoxinine.

Key words

allylic oxidation - asymmetric synthesis - cycloaddition - lactam - natural product

9

(4 R ,5 R )-5-(1-Hydroxyallyl)-4-[( S )-1-(2,4,6-triiso-propylphenyl)ethoxy]pyrrolidin-2-one (9a,b).
TBHP (tert-butylhydroperoxide, 5 M in decane, 1.8 mL, 9.0 mmol) was added to SeO2 (254 mg, 2.27 mmol) in 1,2-dichloroethane (10 mL). The mixture was vigorously stirred at 20 °C for 1.5 h and lactam 8b (1.70 g, 4.58 mmol) in 1,2-dichloroethane (20 mL) was then added rapidly. The resulting mixture was warmed to 70 °C and stirred for 3.3 h. After being allowed to cool to 20 °C, the reaction mixture was treated with an aq solution of NaHCO3 (50 mL), diluted with H2O (30 mL), and extracted with EtOAc (3 × 120 mL). The combined organic extracts were washed with aq Na2SO3 (120 mL), H2O (120 mL), and brine (120 mL), dried over MgSO4, filtered, and concentrated. The resulting oil in 7 mL of EtOH at 0 °C was treated with 171 mg (0.46 mmol) of CeCl3·7H2O, followed by 17.3 mg (0.46 mmol) of NaBH4 (to reduce the 5-10% of enone). After 1 h, the reaction mixture was processed with EtOAc in the usual way and the crude product was purified by flash chromatography on silica gel with EtOAc in CH2Cl2 (40-100%) to afford 440 mg of recovered 8b, followed by 988 mg (56%; 75% based on recovered starting material) of 9a,b as a white solid. Extensive purification of this material over silica gel provided enriched samples of 9a and 9b for spectral data.
Compound 9a: 1H NMR (300 MHz, CDCl3): δ = 7.07 (s, 1 H), 6.99 (s, 1 H), 5.80 (ddd, J = 17.3, 10.7, 4.4 Hz, 1 H), 5.42 (dt, J = 17.3, 1.7 Hz, 1 H), 5.27 (dt, J = 10.7, 1.7 Hz, 1 H), 5.18 (q, J = 6.9 Hz, 1 H), 4.61 (m, 1 H), 4.35 (q, J = 7.5 Hz, 1 H), 3.82 (sept, J = 6.7 Hz, 1 H), 3.65 (dd, J = 7.6, 1.4, 1 H), 3.16 (sept, J = 6.7 Hz, 1 H), 2.87 (sept, J = 6.9 Hz, 1 H), 2.61 (dd, J = 16.7, 6.7 Hz, 1 H), 2.54 (dd, J = 16.6, 7.9 Hz, 1 H), 1.61 (d, J = 6.8 Hz, 3 H), 1.31-1.18 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = 175.4, 149.0, 148.5, 146.8, 136.7, 123.8, 121.3, 117.0, 72.7, 72.1, 70.8, 60.9, 37.7, 34.4, 29.6, 28.6, 25.6, 25.5, 25.4, 24.6, 24.3, 23.6.
Compound 9b: 1H NMR (300 MHz, CDCl3): δ = 7.09 (s, 1 H), 7.00 (s, 1 H), 5.86 (ddd, J = 17.3, 10.5, 6.8 Hz, 1 H), 5.39 (dt, J = 17.3, 1.2 Hz, 1 H), 5.32 (dt, J = 10.4, 1.1 Hz, 1 H), 5.20 (q, J = 6.7 Hz, 1 H), 4.45-4.35 (m, 2 H), 3.72 (sept, J = 6.9 Hz, 1 H), 3.56 (td, J = 7.7, 1.1 Hz, 1 H), 3.38 (d, J = 2.3 Hz, 1 H), 3.17 (sept, J = 6.8 Hz, 1 H), 2.88 (sept, J = 6.9 Hz, 1 H), 2.56 (d, J = 8.0 Hz, 1 H), 1.63 (d, J = 6.8 Hz, 3 H), 1.34-1.18 (m, 18 H). 13C NMR (75 MHz, CDCl3): δ = 174.6, 149.1, 148.7, 146.6, 137.0, 123.8, 121.4, 118.9, 73.6, 73.0, 60.3, 36.6, 34.4, 29.6, 29.0, 25.6, 25.5, 25.3, 24.5, 24.3, 23.5.

10

The relative stereochemistry in 9a and 9b was assigned from the NMR of derivatives prepared in a concomitant project (to be published); these assignments were confirmed by the successful synthesis of (-)-detoxinine.