Synlett 2003(13): 2089-2091  
DOI: 10.1055/s-2003-42041
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Quinolone-Fused Multi-ring-Sized Heterocycles via Combined Claisen Rearrangement/Ring-Closing Metathesis Reactions

Christophe Paina, Sylvain Célanirea, Gérald Guillaumeta, Benoît Joseph*a,b
a Institut de Chimie Organique et Analytique, UMR-CNRS 6005, Université d’Orléans, B.P. 6759, 45067 Orléans Cedex 2, France
b Laboratoire de Chimie Organique 1, UMR-CNRS 5622, Université Claude Bernard - Lyon 1, CPE - Bâtiment 308, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
Fax: +33(4)72431214; e-Mail: benoit.joseph@univ-lyon1.fr;
Further Information

Publication History

Received 7 July 2003
Publication Date:
08 October 2003 (online)

Abstract

Synthetic strategy on 4-quinolone nucleus coupling aza-Claisen rearrangement and ring-closing metathesis was developed. Thus, quinolone-fused multiring-sized oxygen heterocycles 5a-c were prepared from 5-hydroxy-7-methoxy-3-(4-methoxyphenyl)-4(1H)-quinolone (1). According to the same strategy, azepino[2,3-f]quinolone derivative 9 was synthesised from triflate 6.

7

Typical RCM Procedure: Under argon atmosphere, Grubb’s reagent (19.6 mg, 0.02 mmol) was added to a solution of 4a (93 mg, 0.24 mmol) in dry CH2Cl2 (10 mL). The final solution was stirred at r.t. for 2 h. The solvent was evaporated. The residue was purified by column chromatography (petroleum ether-EtOAc, 2:8; then EtOAc) to give 70 mg (81%) of 5a.

8

Physical data of compound 5a: mp 175-176 °C (EtOAc). IR (KBr): ν = 1626, 1609, 1584, 1511 cm-1. 1H NMR (250 MHz, CDCl3): δ = 7.52 (d, 2 H, J = 8.8 Hz, Ar-H), 7.42 (s, 1 H, =CH), 6.89 (d, 2 H, J = 8.8 Hz, Ar-H), 6.36 (s, 1 H, Ar-H), 5.89-5.77 (m, 1 H, CH=), 5.51-5.45 (m, 1 H, CH=), 4.80-4.77 (m, 2 H, CH2), 3.90 (s, 3 H, OCH3), 3.80 (s, 3 H, OCH3), 3.69 (s, 3 H, NCH3), 3.58-3.54 (m, 2 H, CH2). 13C NMR (62.90 MHz, CDCl3): δ = 175.6 (CO), 159.7 (C), 158.7 (C), 158.6 (C), 141.6 (C), 140.4 (CH), 130.1 (2 CH), 128.6 (CH), 128.2 (C), 125.7 (CH), 124.4 (C), 123.1 (C), 115.9 (C), 113.7 (2 CH), 91.7 (CH), 70.2 (CH2), 55.7 (CH3), 55.4 (CH3), 41.4 (CH3), 21.5 (CH2). MS (IS): m/z = 364
(M + H+). Anal. Calcd for C22H21NO4: C, 72.71; H, 5.82; N, 3.85. Found: C, 73.03; H, 5.94; N, 3.77.

9

All new compounds gave satisfactory spectroscopic (1H-, 13C NMR, MS and IR) and analytical data.

10

Physical data of compound 7: mp 119-120 °C (EtOAc). IR (KBr): ν = 3460, 1630, 1610, 1570, 1560, 1512 cm-1. 1H NMR (250 MHz, CDCl3): δ = 10.18 (broad s, 1 H, NH), 7.49 (d, 2 H, J = 7.8 Hz, Ar-H), 7.43 (s, 1 H, =CH), 6.93 (d, 2 H, J = 7.8 Hz, Ar-H), 6.06 (s, 1 H, Ar-H), 6.17-5.89 (m, 2 H, =CH), 5.34-5.25 (m, 1 H, =CH2), 5.08-4.95 (m, 3 H, =CH2), 3.90-3.82 (m, 5 H, OCH3 + CH2), 3.79 (s, 3 H, OCH3), 3.61 (s, 3 H, NCH3), 3.44-3.42 (m, 2 H, CH2). 13C NMR (62.90 MHz, CDCl3): δ = 178.7 (CO), 162.0 (C), 158.6 (C), 154.9 (C), 142.1 (C), 140.2 (C), 137.9 (C), 137.2 (C), 130.1 (2 CH), 128.1 (CH), 121.8 (CH), 115.1 (CH2), 114.4 (CH2), 113.6 (2 CH), 112.0 (CH), 110.7 (C), 86.1 (CH), 55.4 (CH3), 55.3 (CH3), 51.4 (CH2), 41.5 (CH3), 30.2 (CH2). MS (IS):
m/z = 391 (M + H+). Anal. Calcd for C24H26N2O3: C, 73.82; H, 6.71; N, 7.17. Found: C, 73.95; H, 6.60; N, 7.08.

11

Physical data of compound 9: mp 245-246 °C (EtOAc). IR (KBr): ν = 1671, 1635, 1612, 1575, 1513 cm-1. 1H NMR (250 MHz, CDCl3): δ = 7.54 (s, 1 H, =CH), 7.50 (d, 2 H, J = 8.7 Hz, Ar-H), 6.88 (d, 2 H, J = 8.7 Hz, Ar-H), 6.69 (s, 1 H, Ar-H), 5.75-5.68 (m, 1 H, =CH), 5.52-5.40 (m, 2 H, CH2 + =CH), 3.98 (s, 3 H, OCH3), 3.81 (s, 3 H, OCH3), 3.78 (s, 3 H, NCH3), 3.63-3.43 (m, 3 H, CH2), 1.74 (s, 3 H, COCH3). 13C NMR (62.90 MHz, CDCl3): δ = 174.9 (CO), 169.5 (CO), 158.9 (C), 158.6 (C), 142.9 (C), 141.8 (C), 140.8 (CH), 130.1 (2 CH), 128.2 (C+CH), 127.7 (C), 124.2 (CH), 123.3 (C), 117.0 (C), 113.8 (2 CH), 95.6 (CH), 56.0 (CH3), 55.4 (CH3), 43.6 (CH2), 41.6 (CH3), 21.8 (CH3), 21.5 (CH2). MS (IS): m/z = 405 (M + H+). Anal. Calcd for C24H24N2O4: C, 71.27; H, 5.98; N, 6.93. Found: C, 70.99; H, 6.12; N, 6.89.