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Synlett 2002(12): 2007-2010
DOI: 10.1055/s-2002-35582
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of the C1-C11 Segment of Tedanolide via Vinylogous Mukaiyama Aldol Reaction

Jorma Hassfeld, Markus Kalesse*
Institut für Chemie der Freien Universität Berlin, Fachbereich Organische Chemie, Takustrasse 3, 14195 Berlin, Germany
Fax: +49(30)83855644; e-Mail: Kalesse@chemie.fu-berlin.de;
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Publication History

Received 3 September 2002
Publication Date:
20 November 2002 (online)

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Abstract

The successful construction of complex natural products depends to a large extent on how efficiently key intermediates can be generated. Here we report our efforts towards the first total synthesis of tedanolide (1), employing Evans’ aldol methodology in combination with a vinylogous Mukaiyama aldol reaction (VMAR) and Sharpless’ asymmetric dihydroxylation. This protocol allows for rapid access to its numerous chiral centers.

Key words

aldol reactions - Mukaiyama - natural products - dihydroxylations - stereoselective synthesis

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Aldehyde 11 (92 mg, 0.218 mmol) dissolved in diethyl ether (2 mL) was cooled to -78 °C under an argon atmosphere. Tris(pentafluorophenyl)borane (110 mg, 0.217 mmol) was added and a mixture of ketene acetal 12 (100 mg, 0.438 mmol) and isopropyl alcohol (17 µL, 0.24 mmol) dissolved in diethyl ether (1 mL) was added via syringe pump over 6 h. An additional equivalent of ketene acetal 12 (100 mg, 0.438 mmol) was added in diethyl ether (1 mL) over 4 h. After complete addition, the reaction was quenched by sat. aq NaHCO3 (2 mL), slowly warmed to r.t. and stirred overnight. Water (3 mL) was added and the mixture was extracted with ether (2 × 15 mL). The organic layer was separated, dried with MgSO4 and evaporated in vacuo. Flash column chromatography using petroleum ether/ethyl acetate (4:1) as eluent afforded 13 (73 mg, 62%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 8.78 Hz, 2 H), 6.85 (d, J = 8.78 Hz, 2 H), 6.70 (dd, J = 15.69, 9.29 Hz,
1 H), 5.80 (dd, J = 15.69, 0.75 Hz, 1 H), 5.16 (d, J = 9.54 Hz, 1 H), 4.38 (s, 2 H), 3.87 (d, J = 7.44 Hz, 1 H), 3.77 (s,
3 H), 3.70 (s, 3 H), 3.28 (dd, J = 8.90, 5.90 Hz, 1 H), 3.28-3.24 (m, 1 H), 3.18 (dd, J = 8.90, 8.03 Hz, 1 H), 2.77-2.66 (m, 1 H), 2.44-2.36 (m, 2 H), 1.59-1.51 (m, 1 H), 1.53 (d, J = 1.25 Hz, 3 H), 0.97 (d, J = 6.52 Hz, 3 H), 0.90 (d, J = 6.77 Hz, 3 H), 0.85 (d, J = 6.90 Hz, 3 H), 0.85 (s, 9 H), 0.02 (s, 3 H), -0.05 (s, 3 H); 13C NMR (100 MHz, CDCl3):
δ = 166.9, 159.2, 151.0, 136.2, 130.8, 130.3, 129.2, 120.7, 113.8, 82.4, 75.1, 72.7, 55.2, 51.4, 40.8, 39.7, 32.5, 26.9, 25.9, 18.1, 17.1, 16.7, 11.9, 8.1, -4.4, -5.1; HRMS calcd for C30H50O6Si: 534.3377. Found: 534.3371.