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Synlett 2007(11): 1683-1686  
DOI: 10.1055/s-2007-982563
LETTER
© Georg Thieme Verlag Stuttgart · New York

The Catalytic Asymmetric Claisen Rearrangement (CAC) in Natural Product Synthesis: Synthetic Studies Toward (-)-Ecklonialactone B

Qi Wanga, Agnès Milletb, Martin Hiersemann*a
a Universität Dortmund, Fachbereich Chemie, Lehrbereich Organische Chemie, Otto-Hahn-Str. 6, 44227 Dortmund
Fax: +49(231)46336148; e-Mail: martin.hiersemann@uni-dortmund.de;
b Technische Universität Dresden, Fachrichtung Chemie, Organische Chemie, Bergstraße 66, 01062 Dresden
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Publication History

Received 3 May 2007
Publication Date:
25 June 2007 (online)

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Abstract

A catalytic asymmetric Claisen rearrangement (CAC) in concert with a ring-closing metathesis (RCM) has been utilized in the enantioselective synthesis of the C10-C18 segment of ecklonialactone B.

Key words

total synthesis - natural products - asymmetric catalysis - pericyclic reactions - Lewis acids

15

Synthesis of (3 R ,4 R )-4
A stock solution of {Cu[(S,S)-tert-Bu-box]}(H2O)2(SbF6)2 (10) in CF3CH2OH (1 mL, 0.1 M, 86 mg, 0.1 mmol, 0.05 equiv) was dissolved in CH2Cl2 (5 mL). The allyl vinyl ether (E,Z)-5 (0.59 g, 2.0 mmol, 1 equiv) was then added and the solution was stirred over night at r.t. At this point, additional {Cu[(S,S)-tert-Bu-box]}(H2O)2(SbF6)2 (0.5 mL, 0.1 M in CF3CH2OH, 43 mg, 0.05 mmol, 0.025 equiv) was added. The reaction mixture was stirred for 3 d at r.t. and then concentrated under reduced pressure. The catalyst was removed by filtering the crude product mixture through a short path silica gel column. Subsequent flash chromatography (hexane-EtOAc, 50:1) afforded the α-keto ester 4 (0.54 g, 1.8 mmol, 92%) as a light yellow oil. TLC: R f = 0.72 (hexane-EtOAc, 5:1). 1H NMR (400 MHz, CDCl3): δ = 2.32-2.36 (m, 2 H), 2.83 (ddd, J 1 = 19.1 Hz, J 2 = 9.5 Hz, J 3 = 4.8 Hz, 1 H), 3.32 (dd, J 1 = J 2 = 9.7 Hz, 1 H), 3.39-3.47 (m, 2 H), 3.54 (s, 3 H), 4.27 (d, J = 12.1 Hz, 1 H), 4.31 (d, J = 12.1 Hz, 1 H), 4.90-4.97 (m, 2 H), 5.13-5.17 (m, 2 H), 5.52 (ddd, J 1 = 17.4 Hz, J 2 = J 3 = 9.5 Hz, 1 H), 5.64 (dddd, J 1 = 17.1 Hz, J 2 = 10.0 Hz, J 3 = 7.1, J 4 = 7.0 Hz, 1 H), 7.19-7.31 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 34.7 (CH2), 48.2 (CH), 48.2 (CH), 52.4 (CH3), 72.5 (CH2), 72.6 (CH2), 117.2 (CH2), 118.9 (CH2), 127.5 (3 × CH), 128.2 (2 × CH), 134.7 (CH), 135.4 (CH), 137.3 (C), 161.2 (C), 194.7 (C). IR (in substance): 3080-2860, 1730, 1640 cm-1. Anal. Calcd for C18H22O4: C, 71.5; H, 7.3. Found: C, 71.5; H, 7.1. [α]D 25 +46.8 (c 0.68, CHCl3).

19

Synthesis of 3
Diene 11 (36.4 mg, 0.12 mmol, 1 equiv) was dissolved in DCE (2.5 mL) in a septum-sealed round-bottomed flask. The flask was twice evacuated (20 mbar, 2 min) and ventilated with argon. The Grubbs catalyst 12 (1.0 mg, 1.2 µmol, 0.01 equiv) was then added to the solution and the flask was again twice evacuated and ventilated with argon. The reaction mixture was then stirred for 5 h at 40 °C. Silica gel (120 mg) was subsequently added and the heterogeneous mixture was stirred for several minutes. The solid was then removed by filtration and the solvents were evaporated at reduced pressure. The crude product was purified by flash chromatography (hexane-EtOAc, 20:1 to 10:1) to afford the cyclopentenoid 3 (27.6 mg, 0.10 mmol, 84%) as a light yellow oil. TLC: R f = 0.17 (hexane-EtOAc, 5:1). 1H NMR (400 MHz, CDCl3): δ = 2.32 (ddd, J 1 = 15.9 Hz, J 2 = 6.0 Hz, J 3 = 2.1 Hz, 1 H), 2.41 (ddd, J 1 = 15.1 Hz, J 2 = J 3 = 6.3 Hz, 1 H), 2.51 (ddd, J 1 = 15.8 Hz, J 2 = J 3 = 2.3 Hz, 1 H), 2.96-2.98 (m, 1 H), 3.20 (dd, J 1 = J 2 = 8.7 Hz, 1 H), 3.51 (dd, J 1 = 8.8 Hz, J 2 = 5.0 Hz, 1 H), 3.66 (s, 3 H), 4.10 (d, J = 6.8 Hz, 1 H), 4.50 (d, J = 12.2 Hz, 2 H), 4.55 (d, J = 12.2 Hz, 1 H), 5.50 (ddd, J 1 = 3.8 Hz, J 2 = J 3 = 1.9 Hz, 1 H), 5.70 (dd, J 1 = 5.5 Hz, J 2 = 2.3 Hz, 1 H), 7.25-7.35 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 35.7 (CH2), 45.9 (CH), 48.8 (CH), 52.0 (CH3), 73.2 (CH2), 73.5 (CH2), 74.0 (CH), 127.7 (3 × CH), 128.4 (2 × CH), 130.1 (CH), 130.9 (CH), 137.6 (C), 174.4 (C). IR (in substance): 3445, 3060-2855, 1738 cm-1. Anal. Calcd for C16H20O4: C, 69.5; H, 7.3. Found: C, 69.3; H, 7.6. [α]D 25 -58.9 (c 0.56, CHCl3).

22

Synthesis of 2
To a solution of the olefin 17 (79.6 mg, 0.32 mmol, 1 equiv) in CH2Cl2 (12 mL) was added Na2HPO4 (137.7 mg, 0.97 mmol, 3 equiv) and MCPBA (77% purity, 108.7 mg, 0.49 mmol, 1.5 equiv) at 0 °C. The reaction mixture was then stirred for 7 h at r.t. and subsequently quenched with sat. aq Na2SO3 solution. The layers were separated and the aq phase was extracted three times with CH2Cl2. The combined organic phases were dried with MgSO4 and concentrated under reduced pressure. Flash chromatography (hexane-EtOAc, 20:1 to 10:1) afforded the epoxide 2 (56 mg, 0.21 mmol, 66%) and its diastereomer 18 (22 mg, 0.08 mmol, 26%). TLC (hexane-EtOAc, 2:1): R f (18) = 0.41, R f (2) = 0.31.
Compound 2: 1H NMR (400 MHz, CDCl3): δ = 0.92 (dd, J 1 = J 2 = 7.4 Hz, 3 H), 1.26 (ddq, J 1 = 14.2, J 2 = 7.3 Hz, J 3 = 7.1 Hz, 1 H), 1.41 (ddd, J 1 = 13.9 Hz, J 2 = 9.1 Hz, J 3 = 0.7 Hz, 1 H), 1.47-1.59 (m, 2 H), 2.12-2.19 (m, 2 H), 3.26 (ddd, J 1 = 8.5 Hz, J 2 = 8.3 Hz, J 3 = 1.9 Hz, 1 H), 3.40-3.41 (m, 2 H), 3.53 (dd, J 1 = 9.3 Hz, J 2 = 9.1 Hz, 1 H), 3.81 (dd, J 1 = 9.1 Hz, J 2 = 4.5 Hz, 1 H), 4.15 (OH, 1 H), 4.54 (d, J = 12.1 Hz, 1 H), 4.62 (d, J = 12.1 Hz, 1 H), 7.26-7.29 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 9.2 (CH3), 28.0 (CH2), 32.4 (CH2), 44.7 (CH), 45.6 (CH), 55.6 (CH), 59.1 (CH), 71.5 (CH2), 73.5 (CH2), 75.8 (CH), 127.8 (3 × CH), 128.4 (2 × CH), 137.0 (C). IR (in substance): 3430, 3090-2875, 1715 cm-1. Anal. Calcd for C16H22O2: C, 73.3; H, 8.5. Found: C, 72.9; H, 8.6. [α]D 25 -55.1 (c 0.55, CHCl3).