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Synlett 2002(9): 1500-1504
DOI: 10.1055/s-2002-33515
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Approach to the Pyrroloquinoline Core of Martinelline

Richard Malassenea, Lourdes Sanchez-Bajoa, Loic Toupetb, Jean-Pierre Hurvois*a, Claude Moineta
a Laboratoire d’Electrochimie, UMR 6509, Institut de Chimie, Université de Rennes I, Campus de Beaulieu, 35042 Rennes Cedex, France
b Groupe Matière Condensée et Matériaux, Université de Rennes I, Campus de Beaulieu, 35042 Rennes Cedex, France
Fax: +33(223)235967; e-Mail: Jean-Pierre.Hurvois@univ-rennes1.fr;
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Publication History

Received 1 July 2002
Publication Date:
17 September 2002 (online)

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Abstract

The synthesis of α-aminonitrile 4, a potent precursor to the martinellines is described. The preparation of the pyrroloquinoline core was realized in one step (90% yield) using a formal [4π+2π] cyclocondensation involving the cationic aza-diene 6 and the 1-(benzyloxy)carbonyl-2-pyrroline 5 as dienophile. The stereo­chemical outcome of the cyanation procedure performed on the tricyclic core thus obtained is discussed.

Key words

martinelline - stereoselective synthesis - nitriles - natural products

11

5-Ethyl-2,3,3a,4,5,9b-hexahydro-furo-[3,2- c ]quinoline(12):
To a cooled (-80 °C) solution (10 mL, CH2Cl2) containing the aminoacetal 8 (1.0 g, 5.58 mmol) was added dropwise (by syringe) and under an argon atmosphere 0.870 g (6.17 mmol) of BF3·OEt2. The reaction mixture turned slightly green and was stirred at that temperature for one hour. A solution (CH2Cl2, 5 mL) of 2,3-dihydrofuran (0.470 g, 6.71 mmol) was added dropwise over a 5 min period and was allowed to react at -80 °C with the iminium salt 6 for two hours. The crude mixture was quenched with water, and extracted with CH2Cl2 in the presence of Na2CO3. The combined organic layers were dried over MgSO4 and evaporated in vacuo to yield the crude material which was purified by column chromatography (ether/petroleum ether, 1/2) to afford 12 (0.850 g, 75%) as a slightly yellow oil. 1H NMR (300 MHz, CDCl3): δ =1.13 (t, J = 7.10 Hz, 3 H, CH2-CH3), 1.69-1.80 (m, 1 H, 3-Ha), 2.17-2.29 (m, 1 H, 3-Hb), 2.37-2.48 (m, 1 H, 3a-H), 2.85 (t, J = 11.30 Hz, 1 H, 4-Ha), 3.00 (dd, J = 11.30 and 5.35 Hz, 1 H, 4-Hb), 3.27 (dq, J = 14.30 and 7.15 Hz, 1 H, CH2-CH3), 3.50 (dq, J = 14.30 and 7.15 Hz, 1 H, CH2-CH3), 3.80 (td, J = 8.60 and 6.20 Hz, 1 H, 2-Ha), 3.94 (td, J = 8.45 and 5.90 Hz, 1 H, 2-Hb), 4.54 (d, J = 5.35 Hz, 1 H, 9b-H), 6.67-6.72 (m, 2 H), 7.15 (td, J = 9.60 and 1.71 Hz, 1 H), 7.32 (dm, J = 7.00 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 10.60, 30.01, 35.65, 45.29, 49.24, 65.00, 76.08, 111.59, 116.55, 121.28, 129.02, 131.74, 145.42. C13H17NO: Calcd C, 76.81; H, 8.43; N, 6.89; O, 7.87. Found: C, 76.38; H, 8.43; N, 7.13; O, 7.47.

14

A trans fused adduct displaying a coupling constant of 13.80 Hz between 3a-H and 9b-H has been recently isolated in 5% yield and was reported by Lovely and co-workers in ref. [2m]

15

Crystallographic data for the structure cis- 14 reported in this paper has been deposited at the Cambridge Crystallographic Data Center as supplementary publication no: CCDC 186783. Copies of the data can be obtained free of charge on application to The Director CCDC, 12 Union Road, Cambridge CB2 IEZ, UK [fax: +44(1223)336033, e-mail: deposit@ccdc.cam.ac.uk].

16

4-Cyano-5-ethyl-2,3,3a,4,5,9b-hexahydro-pyrrolo[3,2- c ]quinolin-1-carboxylic Acid Benzyl Ester(4):
0.5 g (1.48 mmol) of 3 were dissolved in methanol (50 mL) containing AcOLi (20 g/L) and 0.520 g (10.6 mmol) of NaCN. The amine was oxidized at controlled potential (Ep = +0.75 V/SCE) and after the consumption of 2.0 F per mole of substrate, the electrolysis was stopped. Classical work-up and chromatographic purification (diethyl ether/petroleum ether, 1/2) afforded 4 (0.460 g, 85%) as a pale yellow oil. 1H NMR (300 MHz, C6D6, 343 K): δ = 0.89 (t, J = 7.15 Hz, 3 H, CH2-CH3), 1.21-1.34 (m, 1 H, 3-Ha), 1.44-1.58 (m, 1 H, 3-Hb), 1.94-2.04 (m, 1 H, 3a-H), 2.75-2.87 (dd, J = 15.0 and 7.15 Hz, 1 H, CH2-CH3), 2.90-3.11 (m, 2 H, CH2-CH3 and 2-Ha), 3.29 (d, J = 2.60, 1 H, 4-H), 3.33-3.36 (br, coal., 1 H, 2-Hb), 5.12 (AB, J = 13.40 Hz, 1 H, O-CH2-C6H5), 5.27 (AB, J = 13.40 Hz, 1 H, O-CH2-C6H5), 5.50 (d, J = 7.50 Hz, 1 H, 9b-H, 6.41 (d, J = 8.30 Hz, 1 H), 6.72 (t, J = 8.70 Hz, 1 H), 6.98 (t, J = 8.80 Hz, 1 H), 7.05 (m, 5 H), 7.30-7.33 (m, 2 H). 13C NMR (75 MHz, C6D6, 343 K): δ = 11.99, 26.15, 40.23, 45.05, 45.10, 50.67, 54.70, 67.21, 112.60, 118.88, 119.96, 123.68, 127.72, 128.04, 128.73, 128.98, 131.15, 137.63, 141.34, 156.07. C22H23N3O2: Calcd 361.1790. Found 361.1787 (MS).