Download PDF
Synlett 2009(19): 3214-3218  
DOI: 10.1055/s-0029-1218300
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Association of Intramolecular Furan Diels-Alder Reaction and N-Acylim­­i­n­ium Alkylation for the Synthesis of Pentacyclic Precursor of Aromathecins

Frédéric Pin, Sébastien Comesse, Adam Daïch*
Laboratoire de Chimie, URCOM, EA 3221, CNRS-INC3M FR3038, UFR des Sciences et Techniques, Université du Havre, BP 540, 25 Rue Philipe Lebon, 76058 Le Havre Cedex, France
Fax: +33(2)32744391; e-Mail: adam.daich@univ-lehavre.fr;
Further Information

Publication History

Received 29 May 2009
Publication Date:
21 October 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

A new approach for the synthesis of isoindoloquinoline and aromathecin templates is presented. These were obtained in a few steps starting from inexpensive reagents by two different strategies. The key step for both sequences was the IMFDA reaction, leading diastereoselectively to the formation of the unsaturated DE ring system of the expected alkaloid skeletons.

Key words

benzoindolizino[1,2-b]quinolinone - heterocycle - N-acyl­iminium - α-amidoalkylation - Diels-Alder

15

Data for 2A
Mp 123 ˚C (white solid); R f = 0.27 (cyclohexane-EtOAc = 1:1). IR: ν = 1729 (C=O), 1684 (C=O), 1645 (C=C), 1444 (CH), 1426 (CH), 1290 (CO) cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 1.12-1.24 (m, 1 H, H6 α), 1.20 (t, 3 H, CH3CH2, J = 7.0 Hz), 2.37-2.47 (m, 1 H, H7), 2.63-2.75 (m, 1 H, H6 β), 2.68-2.75 (m, 1 H, H8), 3.70 (d, 1 H, H4 α, J = 15.6 Hz), 4.10 (q, 2 H, CH3CH2, J = 7.0 Hz), 4.41 (dd, 1 H, H5, J = 12.5, 3.1 Hz), 4.90 (d, 1 H, H4 β, J = 15.6 Hz), 5.10 (dd, 1 H, H1, J = 4.7, 1.6 Hz), 6.28 (d, 1 H, H3, J = 5.5 Hz), 6.42 (dd, 1 H, H2, J = 5.5, 1.6 Hz), 7.38-7.55 (m, 3 H, Har), 7.83 (d, 1 H, Har, J = 7.0 Hz). ¹³C NMR (50 MHz, CDCl3): δ = 14.4 (CH3), 36.6 (C6), 39.6 (C7), 41.1 (C4), 53.7 (C8), 57.5 (C5), 61.1 (CH2 ester), 80.1 (C1), 85.7 (Cq), 122.0 (CHar), 124.2 (CHar), 128.6 (CHar), 131.6 (CHar), 132.5 (Cq), 136.7 (C3), 137.7 (C2), 145.2 (Cq), 166.7 (C=O), 171.5 (C=O). Anal. Calcd for C19H19NO4 (325.13): C, 70.14; H, 5.89; N, 4.31. Found: C, 69.98; H, 5.66; N, 4.21.

18

Only traces of product 24 were detected by ¹H NMR.

20

Data for 3A
Mp 159 ˚C (white solid); R f = 0.23 (cyclohexane-EtOAc = 2:3). IR: ν = 2903 (CH), 1731 (C=O), 1692 (C=O), 1636 (C=N), 1508 (C=C) cm-¹. ¹H NMR (200 MHz, CDCl3): δ = 1.21-1.31 (m, 1 H, H11 α), 1.24 (t, 3 H, CH3CH2, J = 7.0 Hz), 2.42-2.53 (m, 1 H, H12), 2.77 (dd, 1 H, H13, J = 4.7, 3.9 Hz), 2.96-3.08 (m, 1 H, H11 β), 3.77 (d, 1 H, H4 α, J = 14.9 Hz), 4.10 (q, 2 H, CH3CH2, J = 7.0 Hz), 4.60 (dd, 1 H, H5, J = 12.1, 2.7 Hz), 5.02 (d, 1 H, H4 β, J = 14.9 Hz), 5.13 (dd, 1 H, H1, J = 3.9, 1.6 Hz), 6.30 (d, 1 H, H3, J = 6.3 Hz), 6.47 (dd, 1 H, H2, J = 6.3, 1.6 Hz), 7.62 (dd, 1 H, H8, J = 7.8, 7.0 Hz), 7.78-7.86 (m, 1 H, H7), 7.98 (d, 1 H, H9, J = 7.8 Hz), 8.14 (d, 1 H, H6, J = 8.6 Hz), 8.62 (s, 1 H, H10). ¹³C NMR (50 MHz, CDCl3): δ 14.4 (CH3), 35.3 (C11), 39.6 (C12), 41.2 (C4), 53.7 (C13), 58.9 (C5), 61.1 (CH2 ester), 80.2 (C1), 85.5 (Cq), 123,8 (Cq), 127.3 (C8), 127.9 (Cq), 129.4 (C6), 129.8 (C9), 131.7 (C7), 133.2 (C10), 137.1 (C3), 137.4 (C2), 149.8 (Cq), 163.2 (C=N), 164.9 (C=O), 171.3 (C=O). Anal. Calcd for C22H20N2O4 (376.41): C, 70.20; H, 5.36; N, 7.44. Found: C, 70.05; H, 5.16; N, 7.28.