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Synlett 2009(4): 573-576  
DOI: 10.1055/s-0028-1087917
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Ruthenium-Mediated Asymmetric Hydrogenation Approach to the Synthesis of Discodermolide Subunits

Christophe Roche, Rémi Le Roux, Mansour Haddad, Phannarath Phansavath*, Jean-Pierre Genêt*
Laboratoire de Synthèse Sélective Organique et Produits Naturels UMR 7573 CNRS, Ecole Nationale Supérieure de Chimie de Paris, 11 Rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
Fax: +33(1)44071062; e-Mail: phannarath-phansavath@enscp.fr; e-Mail: jean-pierre-genet@enscp.fr;
Further Information

Publication History

Received 14 October 2008
Publication Date:
16 February 2009 (online)

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Abstract

The C1-C7 and C9-C14 subunits of (+)-discodermolide have been synthesized using ruthenium-SYNPHOS-mediated asymmetric hydrogenation reactions of β-keto esters to set the C3, C5 and C11 hydroxy-bearing stereocenters with very high levels of diastereoselectivity.

Key words

asymmetric catalysis - hydrogenation - ruthenium - total synthesis - natural products

    References and Notes

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18

Spectroscopic Data for Compound 2
[α]D ²5 +3.6 (c 1.0, CHCl3). ¹H NMR (300 MHz, CDCl3): δ = 5.22 (dq, J = 9.1, 1.1 Hz, 1 H), 4.32 (dd, J = 7.0, 4.1 Hz, 1 H), 2.64 (qd, J = 7.1, 4.1 Hz, 1 H), 2.43-2.50 (m, 1 H), 2.42 (d, J = 1.1 Hz, 3 H), 1.45 (s, 9 H), 1.19 (d, J = 7.1 Hz, 3 H), 1.10 (br s, 18 H), 0.98-1.15 (m, 3 H), 1.01 (d, J = 7.0 Hz,
3 H). ¹³C NMR (75 MHz, CDCl3): δ = 173.0, 137.6, 100.3, 80.2, 75.7, 47.1, 45.3, 33.7, 28.1, 18.3, 16.1, 13.1, 10.9.
IR (film): 1732, 1640, 1257, 883 cm-¹. MS (DCI/NH3):
m/z = 551 [M + H]+, 472 [M + NH4 t-Bu]+.

19

Spectroscopic Data for Compound 10
[α]D ²5 +5.5 (c 1.05, CHCl3). ¹H NMR (300 MHz, CDCl3): δ = 6.23 (d, J = 9.8 Hz, 1 H), 4.28 (dd, J = 6.8, 4.1 Hz, 1 H), 2.52-2.67 (m, 2 H), 1.47 (s, 9 H), 1.13 (d, J = 7.2 Hz, 3 H), 1.10 (s, 18 H), 1.04-1.13 (s, 3 H), 1.07 (d, J = 7.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 172.7, 140.8, 88.8, 80.7, 75.1, 46.9, 42.0, 28.2, 18.2, 15.5, 13.1, 9.4. IR (film): 1733, 1460, 1255, 882 cm-¹. MS (DCI/NH3): m/z = 529 [M + H]+. Anal. Calcd for C21H40Br2O3Si: C, 47.73; H, 7.63. Found: C, 47.81; H, 7.51.

23

Spectroscopic Data for Compound 1
[α]D ²5 -2.5 (c 0.8, CHCl3). ¹H NMR (300 MHz, CDCl3): δ = 9.85 (dd, J = 2.5, 1.3 Hz, 1 H), 4.91 (ddd, J = 10.5, 7.4, 4.0 Hz, 1 H), 3.87 (t, J = 2.3 Hz, 1 H), 2.80 (td, J = 7.5, 2.3 Hz, 1 H), 2.78 (td, J = 16.7, 4.0, 1.3 Hz, 1 H), 2.68 (ddd, J = 16.7, 7.4, 2.5 Hz, 1 H), 2.04-2.15 (m, 1 H), 1.28 (d, J = 7.5 Hz, 3 H), 0.98-1.10 (m, 24 H). ¹³C NMR (75 MHz, CDCl3): δ = 199.5, 173.1, 76.3, 75.0, 46.5, 44.4, 33.6, 18.1, 16.7, 13.9, 12.7. IR (film): 2731, 1735, 1223, 883 cm-¹.
MS (DCI/NH3): m/z = 360 [M + NH4]+, 343 [M + H]+.