Synlett 2011(13): 1821-1826  
DOI: 10.1055/s-0030-1260949
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Acid-Promoted Aza-Cyclization versus π-Cyclization of N-Acyliminium Species into Fused Pyrrolo[1,2-a]imidazolones and Pyrrolo[2,1-a]isoquinolinones

Jean-François Fleury, Pierre Netchitaïlo, Adam Daïch*
Laboratoire de Chimie, URCOM, EA 3221, INC3M CNRS-FR 3038, UFR des Sciences et Techniques, Université du Havre, BP: 540, 25 Rue Philippe Lebon, 76058 Le Havre Cedex, France
Fax: +33(2)32744391; e-Mail: adam.daich@univ-lehavre.fr;
Further Information

Publication History

Received 7 February 2011
Publication Date:
14 July 2011 (online)

Abstract

A new approach for the synthesis of fused imidazolones and isoquinolinones is presented. The key step of this sequence was the interception of an N-acyliminium species with nitrogen or π-aromatic nucleophiles under kinetic vs. thermodynamic control. In addition, in the presence of two π-aromatic nucleophiles, only the six-membered ring closure into pyrroloisoquinolinones occurred.

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20

The ratio of both diastereomers 3a,b considered as kinetic products was estimated by ¹H NMR spectroscopy and is different from that of their amidal congeners 9 in a 7:1 ratio.

21

Data for Compound 3b Isolated in 51% yield as a white solid (EtOAc-cyclohexane = 1:4); mp 136 ˚C; [α]D -20.9 (c 0.81×10, CH2Cl2).
IR (KBr): νmax = 3019, 1687 cm. ¹H NMR (300 MHz, CDCl3): δ = 1.01 (s, 9 H), 3.33 (dd, 1 H, J = 12.0, 8.0 Hz), 4.64 (dd, 1 H, J = 12.3, 7.6 Hz), 4.80 (t, 1 H, J = 7.8 Hz), 7.25-7.38 (m, 5 HAr), 7.51 (t, 1 HAr, J = 7.2 Hz), 7.58 (t,
1 HAr, J = 7.2 Hz), 7.80 (d, 1 HAr, J = 7.2 Hz), 8.16 (d, 1 HAr, J = 7.2 Hz). ¹³C NMR (75 MHz, CDCl3): δ = 28.1, 51.7, 64.7, 75.9, 81.0, 122.8, 125.4, 126.8, 127.7, 128.9, 131.8, 132.7, 144.3, 153.6, 179.9. MS (EI): m/z = 350 [M+]. Anal. Calcd (%) for C21H22N2O3 (350.16): C, 71.98; H, 6.33; N, 7.99. Found: C, 71.77; H, 6.18; N, 7.76.

27

Data for Compound 15a Isolated in 35% yield as an orange solid (EtOAc-cyclohexane = 2:3; R f  = 0.17); mp 171 ˚C; [α]D -212.4 (c 1.45×10, CH2Cl2). IR (KBr): νmax = 3019, 1686 cm. ¹H NMR (300 MHz, CDCl3): δ = 2.02-20.7 (m, 1 H), 2.35-2.56 (m, 3 H), 3.91-4.03 (m, 1 H), 4.30 (s, 2 H), 4.81 (s, 1 H), 5.59 (s, 1 H), 7.12-7.24 (m, 5 HAr), 7.30-7.33 (m, 4 HAr), 7.44-7.48 (t, 1 HAr, J = 6.6 Hz), 7.56 (d, 1 HAr, J = 6.0 Hz), 7.67 (d, 1 HAr, J = 7.2 Hz), 7.75 (d, 1 HAr, J = 7.2 Hz). ¹³C NMR (75 MHz, CDCl3): δ = 29.8, 31.5, 39.3, 51.6, 59.1, 66.6, 123.7, 124.2, 126.0, 126.4, 127.3 (2×), 127.6, 127.8, 128.8, 129.2, 129.6 (2×), 132.0, 132.5, 134.4, 135.0, 140.9, 145.0, 167.5, 175.7. MS (EI): m/z = 394 [M+]. Anal. Calcd (%) for C26H22N2O2 (394.48): C, 79.16; H, 5.62; N, 7.10. Found: C, 79.06; H, 5.52; N, 7.05.
Data for Compound 15b Isolated in 31% yield as an orange solid (EtOAc-cyclohexane = 2:3; R f  = 0.11); mp 216 ˚C; [α]D -210.9 (c 0.82×10, CH2Cl2). IR (KBr): νmax = 3019, 1676 cm. ¹H NMR (300 MHz, CDCl3): δ = 1.50-1.57 (m, 1 H), 2.30-2.48 (m, 2 H), 2.50-2.65 (m, 1 H), 3.53 (dd, 1 H, J = 14.1, 3.7 Hz), 4.19 (d, 1 H, J = 8.0 Hz), 4.78 (dd, 1 H, J = 14.1 Hz), 5.54-5.56 (m, 2 H), 6.23-6.29 (m, 2 HAr), 6.56 (t, 2 HAr, J = 7.1 Hz), 6.71 (t, 1 HAr, J = 7.1 Hz), 6.84 (t, 1 HAr, J = 7.4 Hz), 6.98 (d, 1 HAr, J = 7.4 Hz), 7.13 (t, 1 HAr, J = 7.4 Hz), 7.46 (d, 1 HAr, J = 7.4 Hz), 7.55 (t, 1 HAr, J = 7.2 Hz), 7.63 (t, 1 HAr, J = 7.2 Hz), 7.81 (t, 1 HAr, J = 7.2 Hz), 7.95 (d, 1 HAr, J = 7.2 Hz). ¹³C NMR (75 MHz, CDCl3): δ = 29.2, 29.8, 42.1, 50.4, 58.9, 61.8, 123.4, 124.1, 125.0, 125.7 (2×), 126.7, 127.1, 127.8 (2×), 128.6, 129.0, 131.7, 132.1, 132.3, 132.9, 133.9, 141.8, 143.7, 167.9, 176.6; MS (EI): m/z = 394 [M+]. Anal. Calcd (%) for C26H22N2O2 (394.48): C, 79.16; H, 5.62; N, 7.10. Found: C, 78.96; H, 5.50; N, 6.93.