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Synlett 2007(15): 2375-2378  
DOI: 10.1055/s-2007-985606
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Enantiomerically Pure Dihydrofurans and Dihydropyrans from Common Precursors Using RCM and Tandem RCM-Isomerization

Bernd Schmidt*, Anne Biernat
Institut für Chemie, Organische Chemie II, Universität Potsdam, Karl-Liebknecht-Straße 24-25, Haus 25, 14476 Golm, Germany
Fax: +49(331)9775059; e-Mail: bernd.schmidt@uni-potsdam.de;
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Publication History

Received 6 June 2007
Publication Date:
23 August 2007 (online)

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Abstract

Starting from glyceraldehyde, structurally and stereo­chemically diverse dihydrofurans and dihydropyrans with a 1,2-dihydroxyethylene side chain can be accessed in few steps via allyl metal addition, O-allylation and ring-closing metathesis (RCM) or tandem RCM-isomerization, respectively. The synthesis of di­hydrofurans requires a selective double-bond isomerization on the homoallylic alcohol stage, prior to O-allylation and RCM or RCM-isomerization.

Key words

carbohydrates - isomerizations - metathesis - ruthenium - tandem reactions

32

RCM of dienes 7 has very recently been described in a different context, while our work was in progress. See ref. 30.

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Synthesis of Cyclic Enol Ethers 9 and 18: To a solution of the corresponding diene (1.0 mmol) in toluene (10 mL) was added [Cl2(PCy3)2Ru=CHPh] (41 mg, 5 mol%). The solution was stirred at 40 °C until the starting material was fully consumed (approximately 30 min, TLC), and 2-propanol (1 mL/mmol) and NaOH (0.25 equiv) were added. The solution was then heated to reflux until the RCM product was completely converted into the enol ether. The reaction mixture was diluted with MTBE and washed with H2O. The organic layer was separated, dried with MgSO4, filtered, and evaporated. Column chromatography on silica yielded the dihydropyrans or the dihydrofurans. (R,R)-9: [α]23 D -45 (c = 0.9, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 6.41 (d, J = 6.0 Hz, 1 H, H6), 4.69 (m, 1 H, H5), 4.18 (ddd, J = 6.6, 6.6, 6.6 Hz, 1 H, OH2CCHO), 4.03 (dd, J = 6.6, 8.2 Hz, 1 H, OH 2CCHO), 3.82 (ddd, J = 2.7, 6.6, 9.3 Hz, 1 H, H2), 3.75 (dd, J = 7.1, 8.2 Hz, 1 H, OH 2CCHO), 1.90-2.17 (2 H, H4), 1.22-1.78 [12 H, H3, (CH2)5]. 13C NMR (75 MHz, CDCl3): δ = 143.6, 110.2, 100.4, 77.0, 75.7, 65.1, 35.9, 34.9, 25.1, 23.9, 23.8, 23.5, 19.4. HRMS: m/z [M+ + Na] calcd for C13H20O3Na: 247.1310; found: 247.1308.
(R,R)-18: [α]24 D 51 (c = 0.9, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 6.25 (ddd, J = 2.4, 2.4, 2.4 Hz, 1 H, H5), 4.89 (ddd, J = 2.4, 2.4, 2.4 Hz, 1 H, H4), 4.48 (ddd, J = 6.8, 6.8, 10.3 Hz, 1 H, H2), 4.03-4.13 (2 H, OH 2CCHO), 3.86 (m, 1 H, OH2CCHO), 2.72 (dddd, J = 2.4, 2.4, 10.3, 15.4 Hz, 1 H, H3), 2.55 (dddd, J = 2.4, 2.4, 6.9, 15.4 Hz, 1 H, H3′), 1.40-1.70 [10 H, (CH2)5]. 13C NMR (75 MHz, CDCl3): δ = 144.9, 109.9, 99.3, 81.2, 76.4, 66.5, 36.4, 34.8, 31.7, 25.2, 24.0, 23.8. HRMS: m/z [M + H]+ calcd for C12H19O3: 211.1334; found: 211.1331.