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Synlett 2005(15): 2313-2316  
DOI: 10.1055/s-2005-872657
LETTER
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Access to the Spirotetronate Subunit of the Quartromicins

Olivier Bedel*a, Antoine Françaisa, Arnaud Haudrechyb
a Laboratoire de Synthèse des Substances Naturelles, Associé au CNRS, Bât. 410, Université de Paris Sud, 91405 Orsay Cedex, France
b Laboratoire de Glycosynthèse, UMR 6519, UFR Sciences Exactes et Naturelles, Bât. 18, BP 1039, 51687 Reims Cedex 2, France
Fax: +33(3)26913166; e-Mail: arnaud.haudrechy@univ-reims.fr;
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Publikationsverlauf

Received 27 June 2005
Publikationsdatum:
05. August 2005 (online)

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Abstract

The agalacto-spirotetronate B subunit of quartromicins was synthesized in a predictible manner, following the Claisen-­Ireland/metathesis approach (CIM strategy). Ene-yne ring-closure and selective mismatch Sharpless dihydroxylation are discussed as key steps, allowing an efficient approach to these structures.

Key words

quartromicin - ene-yne metathesis - Claisen-Ireland ­rearrangement - asymmetric dihydroxylation - spirotetronate

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Typical CIM Procedure.
Ester 4 (900 mg, 1.34 mmol) was dissolved in dry toluene (17 mL) under argon and then cooled to -78 °C. A solution of KHMDS in toluene (0.5 M) was added dropwise (4 mL, 2 mmol, 1.5 equiv) during 15 min. After 45 min, freshly distilled TMSCl (540 µL) was added and the resulting mixture was stirred for 5 min. Then, the mixture was warmed to r.t. and stirred for additional 3 h. The mixture was hydrolyzed with a 10% NH4Cl (aq) solution and the layers were separated. The aqueous layer was extracted with Et2O (3 × 20 mL), and the combined organic layers were dried, filtered, and the solvent was removed under reduced pressure. The crude product was esterified with diazomethane, and after evaporation dissolved in MeOH (15 mL). Excess of solid K2CO3 (5.4 mmol, 630 mg, 4 equiv) was added in one portion and this suspension was stirred overnight at r.t. After evaporation under reduced pressure, the product was dissolved in Et2O (30 mL) and washed with H2O (15 mL). The layers were separated and the aqueous one was extracted with Et2O (2 × 25 mL). The combined organic layers were dried, filtered and concentrated.
The compound was dissolved in toluene (40 mL) under an argon atmosphere, and a solution of second generation Grubbs’ catalyst (90 mg, 0.105 mmol, 0.08 equiv) in toluene (5 mL) was then added. This solution was heated to 80 °C for 1 h. After cooling down, the mixture was concentrated, and the crude product was purified by silica gel column chromatography (175 g SiO2, Et2O-n-pentane, 1:5) to afford pure cyclized methyl ester 3 (747 mg, 73% yield for four steps).
Data for compound 3: 1H NMR (250 MHz, CDCl3): δ = 7.66 (4 H, m, CAr-H), 7.38 (6 H, m, CAr-H), 7.05 (2 H, d, CMPMar-H, J = 8.5 Hz), 6.74 (2 H, d, CMPMar-H, J = 8.5 Hz), 5.90-6.05 (1 H, m, C4-CHCHMe), 5.74 (1 H, s, C3-H), 5.55-5.70 (1 H, m, C4-CHCHMe), 4.02-4.46 (2 H, AB syst., Ar-CH 2 ), 3.95-4.10 (2 H, m, C2-CH 2 -OSi), 3.78 (3 H, s, OMe), 3.57 (3 H, s, COOMe), 2.71 (1 H, m, C5-H), 2.25-2.35 (1 H, m, C6-Ha), 2.00-2.09 (1 H, m, C6-Hb), 1.78 (3 H, d, C4-CHCHMe, J = 6.25 Hz), 1.16 (3 H, d, C5-Me, J = 7.25 Hz), 1.11 (9 H, s, t-Bu), 1.03 (3 H, s, C2-Me) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 173.4 (COOMe), 158.6 (C qAr -OMe), 136.7 (C4), 135.7 (CAr), 134.0 (C MPMar -CH2O), 133.8 (CqAr), 132.7 (C3), 130.5 (C4-CHCHMe), 129.3 (CAr), 128.0 (CAr), 127.4 (CAr), 123.2 (C4-CHCHMe), 113.5 (CAr), 84.3 (C1), 67.6 (CMPMar-CH2O), 65.8 (C2-CH2-OSi), 55.2 (ArOMe), 51.3 (COOMe), 43.8 (C2), 30.7 (C5), 28.1 (C6), 26.9 (SiCMe 3 ), 21.9 (C2-Me), 20.4 (C5-Me), 17.0 (SiCMe3) ppm. [α]D 20 +17.3 (c 1.2, CHCl3). HRMS (ES): m/z calcd [M + Na]: 635.3169; found: 635.3183.

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Data for compound 14: 1H NMR (250 MHz, CDCl3): δ = 7.66 (4 H, m, CAr-H), 7.35 (6 H, m, CAr-H), 5.44 (1 H, br d, C3-H), 5.16 (1 H, s, CO-CH), 5.01 (2 H, 2 collapsed d, O-CH2-O), 4.25 (1 H, d, C4-CH 2 -OSi, J = 12.8 Hz), 4.08 (1 H, d, C4-CH 2 -OSi), 3.73 (1 H, d, C2-CH 2 -OSi, J = 9.5 Hz), 3.63 (1 H, d, C2-CH 2 -OSi, J = 9.5 Hz), 3.37 (3 H, s, OMe), 2.77 (1 H, m, C5-H), 2.13 (1 H, dd, C6-Ha, J = 9.8 Hz, J = 13.7 Hz), 1.89 (1 H, dd, C6-Ha, J = 7 Hz, J = 13.7 Hz), 1.05 (24 H, m, C5-Me, C2-Me, 2 t-Bu) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 182.7 (CO-CH2-O), 172.2 (CO), 139.9 (C4), 135.9 (CAr), 135.8 (CAr), 135.6 (CAr), 134.0 (CAr), 133.8 (CAr), 133.4 (CAr), 129.9 (CAr), 129.8 (CAr), 129.7 (CAr), 127.8 (CAr), 127.7 (CAr), 126.8 (C3), 96.9 (OMe), 91.2 (CO-CH), 87.4 (O-CH2-O), 70.2 (C4-CH2-OSi),, 66.0 (C2-CH2-OSi), 57.5 (C1), 42.5 (C2), 38.2 (C5), 29.8 (C6) 29.2 (C5-Me), 27.0 (C2-Me), 26.9 (2 SiCMe 3 ), 19.5 19.4 (SiCMe3). [α]D 20 -3.2 (c 0.3, CHCl3). HRMS (ES): m/z calcd [M + H]: 775.3850; found: 775.3875.

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Bedel, O. PhD Thesis, personal results.