Download PDF
Synlett 2003(9): 1367-1369
DOI: 10.1055/s-2003-40326
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Exploration of the Potential of [4+2] Cycloadditions of α-Pyrones with Indenones for the Synthesis of the Norditerpenoid Tropone, Harringtonolide

Lewis N. Mander*, Timothy P. O’Sullivan
Research School of Chemistry, Institute of Advanced Studies, Australian National University, Canberra, ACT, 0200, Australia
Fax: +61(2)61258114; e-Mail: mander@rsc.anu.edu.au;
Further Information

Publication History

Received 14 February 2003
Publication Date:
30 June 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The Diels-Alder reactions of 5-methoxyindenones with various α-pyrones provide the basis for a new and more efficient approach to the synthesis of the unusual nor-diterpenoid tropone, harringtonolide.

Key words

cycloaddition - α-pyrone - indenone - ether formation - tropone

7

The indenone 5 (R1 = H) (550 mg, 3.44 mmol) and the pyrone 6 (R2 = H) (504 mg, 3.27 mmol) were dissolved in CH2Cl2 (1 mL). The reaction mixture was then subjected to high pressure (19 kbar) for 24 h. The solvent was removed under reduced pressure and the residue was chromato-graphed on silica gel (petroleum ether 40-60 °C:EtOAc =
3 : 1) to yield the cycloadduct 7 (R = H) (736 mg, 72%, based on pyrone). Recrystallization from EtOAc afforded colourless crystals. Mp 131-133 °C. IR: νmax (CHCl3): 1763 (s), 1740 (s), 1705 (s), 1597 (s), 1491 (w), 1458 (w), 1439 (w), 1350 (w), 1308 (m), 1284 (m), 1256 (s), 1196 (w), 1169 (w), 1127 (w), 1109 (w), 1092 (m), 1077 (m), 1069 (m), 1024 (w), 981 (w), 962 (w), 740 (w)cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.62 (1 H, d, J 8,7 = 8.6 Hz, H-8), 6.94 (1 H, dd, J 7,8 = 8.6 Hz, J 7,5 = 2.2 Hz, H-7), 6.51 (1 H, d, J 5,7 = 2.0 Hz, H-5), 6.36 (2 H, m, H-10, H-11), 5.45 (1 H, ddd, J 1,9a = 5.0 Hz, J 1,11 = 5.4 Hz, J 1,10 = 2.0 Hz, H-1), 4.32 (1 H, d, J 4a,9a = 7.1 Hz, H-4a), 4.03 (3 H, s, COOCH3), 3.85 (3 H, s, CH3O-C6), 3.63 (1 H, dd, J 9a,4a = 7.1 Hz, J 9a,1 = 5.0 Hz, H-9a). 13C NMR (75 MHz, CDCl3): δ = 199.0 (C9), 169.5 (C3), 168.1 (C12), 166.1 (C6), 154.0 (C4b), 132.0 (C8a), 130.6 (C11), 129.8 (C10), 126.2 (C8), 117.1 (C5), 109.9 (C7), 74.9 (C1), 59.9 (C4), 56.1 (CH3O-C6), 53.7 (COOCH3), 52.8 (C9a), 39.50 (C4a). LRMS: m/z (%) = 314 (24) [M+], 268 (3), 242 (27), 226 (4), 211 (100), 168 (20), 160 (93), 139 (29), 134 (29), 123 (6), 106 (35), 91 (3), 77 (10), 63 (26). HRMS (EI): Found 314.0787 [M+], C17H14O6 requires 314.0790. Anal. Calcd for C17H14O6: C, 64.97%; H, 4.49%. Found: C, 64.51%; H, 4.79%. The high-pressure reactor was purchased from PSIKA Pressure Systems Ltd. This equipment consisted of an electrohydraulic station controlling two hydraulic presses which pressed against two pistons. The two pistons placed pressure on either side of a central hollow chamber that contains the teflon reaction vessel suspended in a castor oil mix (15% methanol/85% castor oil). The ease with which traces of acid induce indenones to dimerize and the thermal instability of α-pyrone adducts mandates the use of high pressure to drive this kind of cycloaddition.

17

FMO calculations were performed on the Spartan (v5.01) program with the RHF/PM3 model.