Synlett 2007(6): 0983-0985  
DOI: 10.1055/s-2007-973867
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Route to the Tetrahydrofuran Segment of Amphidinolides X and Y, and Its Quaternary-Carbon Epimer

Huynh Dong Doan, Julien Gallon, Alexandre Piou, Jean-Michel Vatèle*
Université Claude Bernard, ESCPE, Laboratoire de Chimie Organique 1, UMR 5181 CNRS, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France
Fax: +33(4)72431214; e-Mail: vatele@univ-lyon1.fr;
Further Information

Publication History

Received 25 November 2006
Publication Date:
26 March 2007 (online)

Abstract

A short approach to the tetrahydrofuran fragment of amphidinolides X and Y has been developed through the combination of iterative Sharpless asymmetric epoxidations, Pd-catalyzed regio­selective hydrogenolysis of a 4,5-epoxy-2-alkenoate and the disfavored 5-endo-tet ring closure of a β-hydroxy epoxide promoted by a double bond adjacent to the epoxide function.

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Physical data for 7: liquid; [α]D 20 +8.5 (c = 2, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 3 H), 1.25 (s, 3 H), 1.29-1.62 (m, 4 H), 2.84 (dd, J = 4.8, 6.8 Hz, 1 H), 2.94 (q, J = 4.2, 6.7 Hz, 1 H), 3.64 (ddd, J = 4.7, 7.1, 12.2 Hz, 1 H), 3.80 (ddd, J = 4.2, 7.4, 12.2 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 14.0, 16.7, 18.3, 40.6, 61.4 (2 × C), 63.2. Anal. Calcd for C7H14O2: C, 64.58; H, 10.84; O, 24.58. Found: C, 64.53; H, 10.77; O, 24.21.

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Enantiomeric excess was determined by 1H NMR analysis (C6D6, 300 MHz) of the corresponding acetate of 7, in the presence of the chiral shift reagent Eu(hfc)3.

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Physical data for 5: oil; [α]D 20 -12 (c = 1, CHCl3). 1 NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 7.0 Hz, 3 H), 1.24 (s, 3 H), 1.27 (t, J = 7.1 Hz, 3 H), 1.35-1.66 (m, 4 H), 3.29 (dd, J = 0.9, 6.4 Hz, 1 H), 4.18 (q, J = 7.1 Hz, 2 H), 6.07 (dd, J = 0.9, 15.7 Hz, 1 H), 6.81 (dd, J = 6.5, 15.7 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 14.0, 14.2, 16.5, 18.4, 40.5, 60.6, 61.3, 64.2, 124.8, 143.0, 165.7. Anal. Calcd for C11H18O3: C, 66.64; H, 9.15; O, 24.24. Found: C, 66.60; H, 9.38; O, 24.01.

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A small amount of its corresponding Z-isomer was also isolated (5%).

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Physical data for 8: oil; [α]D 20 -3.0 (c = 2, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 0.89 (t, J = 6.8 Hz, 3 H), 1.16 (s, 3 H), 1.26 (t, J = 7.1 Hz, 3 H), 1.33-1.46 (m, 4 H), 1.91 (s, 1 H), 2.32 (dd, J = 1.0, 7.8 Hz, 2 H), 4.15 (q, J = 7.1 Hz, 2 H), 5.83 (dt, J = 1.2, 15.6 Hz, 1 H), 6.97 (quint, J = 7.8, 15.6 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 14.2, 14.5, 17.0, 27.0, 44.4, 44.8, 60.3, 72.5, 124.2, 144.9, 166.4. Anal. Calcd for C11H20O3: C, 65.97; H, 10.07; O, 23.97. Found: C, 65.72; H, 10.22; O, 24.05.

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Low diastereoselectivity was observed when the epoxidation was conducted with MCPBA (20% de).

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Analytical data for 3: oil; [α]D 20 -20.1 (c = 1.2, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.0 Hz, 3 H), 1.32 (s, 3 H), 1.20-1.50 (m, 4 H), 1.71 (dd, J = 6.4, 12.8 Hz, 1 H), 2.16 (dd, J = 7.4, 12.8 Hz, 1 H), 2.36 (br s, 1 H), 4.02 (q, J = 6.4 Hz, 1 H), 4.13 (t, J = 6.4 Hz, 1 H), 5.18 (dd, J = 0.9, 10.3 Hz, 1 H), 5.34 (dt, J = 1.3, 17.1 Hz, 1 H), 5.83 (ddd, J = 6.7, 10.3, 17.1 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 14.6, 17.8, 27.2, 45.1 (2 × C), 76.8, 82.6, 85.3, 117.1, 137.2. Anal. Calcd for C10H18O2: C, 70.55; H, 10.66; O, 18.8. Found: C, 70.35; H, 10.82; O, 18.82. Analytical data for 11: oil; [α]D 20 -16.3 (c = 1, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 0.92 (t, J = 7.0 Hz, 3 H), 1.21 (s, 3 H), 1.35 (m, 2 H), 1.57 (m, 2 H), 1.84 (dd, J = 7.1, 12.5 Hz, 1 H), 2.05 (dd, J = 6.7, 12.5 Hz, 1 H), 2.28 (br s, 1 H), 4.04 (m, 2 H), 5.19 (dt, J = 0.9, 10.2 Hz, 1 H), 5.34 (dt, J = 0.8, 17.2 Hz, 1 H), 5.84 (ddd, J = 6.7, 10.2, 17.2 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 14.7, 17.9, 27.8, 44.4, 45.2, 76.4, 82.4, 85.7, 117.4, 137.6. Anal. Calcd for C10H18O2: C, 70.55; H, 10.66; O, 18.8. Found: C, 70.77; H, 10.52; O, 18.69.

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[α]D 20 -43.7 (c = 1.6, CHCl3); lit.5 [α]D 20 -37.1 (c = 1, CHCl3, 83% ee); lit.8 [α]D 20 -52.2 (c = 0.8, CHCl3, >96% ee).

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[α]D 20 -45.3 (c = 1.8, CHCl3); lit.5 [α]D 20 -43.5 (c = 0.97, CHCl3, 83% ee).