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Synlett 2010(4): 547-550  
DOI: 10.1055/s-0029-1219181
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Synthesis of (S)-(-)-Umbelactone and Related α,β-Butenolides

William P. D. Goldring*, John Mann, Paul Brockbank
School of Chemistry and Chemical Engineering, Queen’s University Belfast, David Keir Building, Stranmillis Road, Belfast, Northern Ireland BT9 5AG, United Kingdom
Fax: +44(0)2890976524; e-Mail: w.goldring@qub.ac.uk;
Further Information

Publication History

Received 14 October 2009
Publication Date:
15 January 2010 (online)

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Abstract

The development of an asymmetric route for the synthesis of α,β-butenolide building blocks, starting from commercially available d-mannitol, is described. The devised route was applied to a synthesis of the (S)-(-)-enantiomer of the antiviral natural product umbelactone, together with the construction of other synthetically useful lactone structures.

Key words

umbelactone - butenolide - chiral pool - antiviral agents - lactones

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16

Full experimental details for the compounds 2, 18, 23 and (S)-(-)-1, including proton and carbon NMR spectra, are available in the Supporting Information. The following spectroscopic data were recorded for key intermediates.
1-[( R )-2,2-Dimethyl-1,3-dioxolan-4-yl]-4-(4-methoxy-benzyloxy)butan-1-one (5). [α]D ²0 +1.6 (c 1.2 in CHCl3); IR(film): 2988, 2935, 2860, 1716, 1612, 1513, 1456, 1373, 1302, 1210 cm-¹; ¹H NMR (300 MHz, CDCl3): δ = 7.25-7.22 (m, 2 H, ArH), 6.89-6.83 (m, 2 H, ArH), 4.40 (s, 2 H, OCH2PMP), 4.23 (dd, J = 7.7, 5.7 Hz, 1 H, OCHHCH), 4.17 (dd, J = 8.7, 8.0 Hz, 1 H, CH), 3.95 (dd, J = 8.7, 5.7 Hz, 1 H, OCHHCH), 3.80 (s, 3 H, OCH3), 3.45 (t, J = 6.2 Hz, 2 H, PMBOCH2), 2.70 (t, J = 7.2 Hz, 2 H, COCH2), 1.92-1.83 (m, 2 H, PMBOCH2CH 2), 1.47 (d, J = 0.6 Hz, 3 H, CH3), 1.38 (d, J = 0.6 Hz, 3 H, CH3); ¹³C NMR (75 MHz, CDCl3): δ = 210.4, 159.1, 130.4, 129.2, 113.7, 110.8, 80.2, 72.5, 68.8, 66.5, 55.2, 35.4, 26.0, 25.0, 23.1; HRMS (EI): m/z [M]+ calcd for C17H24O5: 308.1624; found: 308.1647 (5%).


1-[( R )-2,2-Dimethyl-1,3-dioxolan-4-yl]pent-4-en-1-one (9). [α]D ²0 +14.9 (c 1.0 in CHCl3); IR(film): 3079, 2988, 2934, 1716, 1641, 1373, 1217, 1068 cm-¹; ¹H NMR (300 MHz, CDCl3): δ = 5.82 (ddt, J = 16.8, 10.4, 6.4 Hz, 1 H, H2C=CH), 5.08-4.95 (m, 2 H, C=CH2), 4.43 (dd, J = 5.5, 2.3 Hz, 1 H, OCHH), 4.19 (t, J = 7.7 Hz, 1 H, CH), 3.98 (dd, J = 5.5, 2.3 Hz, 1 H, OCHH), 2.74-2.68 (m, 2 H, COCH2), 2.37-2.29 (m, 2 H, H2C=CHCH 2), 1.48 (s, 3 H, CH3), 1.39 (s, 3 H, CH3); ¹³C NMR (75 MHz, CDCl3): δ = 210.1, 136.9, 115.3, 110.9, 80.2, 66.5, 37.7, 26.9, 26.0, 25.0.
4-( tert -Butyldimethylsilanyloxy)-1-[( R )-2,2-dimethyl-1,3-dioxolan-4-yl]butan-1-one (10). [α]D ²0 -0.4 (c 1.1 in CHCl3); IR(film): 2932, 2859, 1718, 1255, 1101 cm-¹; ¹H NMR (300 MHz, CDCl3): δ = 4.44 (dd, J = 7.7, 5.6 Hz, 1 H, OCHH), 4.19 (dd, J = 8.7, 7.7 Hz, 1 H, CH), 3.98 (dd, J = 8.7, 5.7 Hz, 1 H, OCHH), 3.62 (t, J = 6.0 Hz, 2 H, TBSOCH2), 2.69 (t, J = 7.0 Hz, 2 H, COCH2), 1.83-1.74 (m, 2 H, TBSOCH2CH 2), 1.48 (s, 3 H, CH3), 1.39 (s, 3 H, CH3), 0.88 (s, 9 H, Si(CH3)3), 0.03 (s, 6 H, Si(CH3)2); ¹³C NMR (75 MHz, CDCl3): δ = 210.8, 110.9, 80.3, 66.5, 62.0, 35.0, 26.0, 25.9, 25.0, 18.3, -5.4; HRMS (ES): m/z [M + Na]+ calcd for C15H30O4SiNa: 325.1811; found: 325.1834 (20%).
tert -Butyl-{4-[( S )-2,2-dimethyl-1,3-dioxolan-4-yl]pent-4-enyloxy}dimethylsilane (11). [α]D ²0 +6.0 (c 0.9 in CHCl3); IR(film): 2928, 2857, 1650, 1471, 1379, 1256, 1214 cm-¹; ¹H NMR (300 MHz, CDCl3): δ = 5.15 (br s, 1 H, C=CHH), 4.90 (t, J = 0.7 Hz, 1 H, C=CHH), 4.53 (t, J = 7.5 Hz, 1 H, OCHH), 4.11 (dd, J = 8.0, 6.5 Hz, 1 H, CH), 3.65-3.58 (m, 3 H, OCHH and TBSOCH2), 2.13-1.97 (m, 2 H, H2C=CCH 2),
1.74-1.64 (m, 2 H, TBSOCH2CH 2), 1.44 (m, 3 H, CH3), 1.40 (s, 3 H, CH3), 0.89 (s, 9 H, Si(CH3)3), 0.04 (s, 6 H, Si(CH3)2); ¹³C NMR (75 MHz, CDCl3): δ = 146.7, 111.1, 109.6, 79.4, 69.4, 63.1, 31.5, 28.1, 26.8, 26.3, 26.1, 18.7,
-4.9.