Stereoselective Approach to the Pyrroloquinoline Core of Martinelline

Richard  Malassene; Lourdes  Sanchez-Bajo; Loic  Toupet; Jean-Pierre  Hurvois; Claude  Moinet

doi:10.1055/s-2002-33515

LETTER

Stereoselective Approach to the Pyrroloquinoline Core of Martinelline

Richard Malassene^a, Lourdes Sanchez-Bajo^a, Loic Toupet^b, Jean-Pierre Hurvois*^a, Claude Moinet^a
^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;

Abstract

All articles of this category

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

Full Text

References

<A NAME="RG18302ST-1">1</A> Witherup KM. Ransom RW. Graham AC. Bernard AM. Salvatore MJ. Lumma WC. Anderson PS. Pitzenberger SM. Varga SL. J. Am. Chem. Soc. 1995, 117: 6682

<A NAME="RG18302ST-2A">2a</A> Ho TCT. Jones K. Tetrahedron 1997, 53: 8287

<A NAME="RG18302ST-2B">2b</A> Gurjar MK. Pal S. Rao AVR. Heterocycles 1997, 45: 231

<A NAME="RG18302ST-2C">2c</A> Lovely CJ. Mahmud H. Tetrahedron Lett. 1999, 40: 2079

<A NAME="RG18302ST-2D">2d</A> Batey RA. Simoncic PD. Lin D. Smyj RP. Lough AJ. Chem. Commun. 1999, 651

<A NAME="RG18302ST-2E">2e</A> Snider BB. Ahn Y. Foxman BM. Tetrahedron Lett. 1999, 40: 3339

<A NAME="RG18302ST-2F">2f</A> Nieman JA. Ennis MD. Org. Lett. 2000, 2: 1395

<A NAME="RG18302ST-2G">2g</A> Nyerges M. Fejes I. Toke L. Tetrahedron Lett. 2000, 41: 7951

<A NAME="RG18302ST-2H">2h</A> Franck KE. Aubé J. J. Org. Chem. 2000, 65: 655

<A NAME="RG18302ST-2I">2i</A> Hadden M. Nieuwenhuyzen M. Osborne D. Stevenson PJ. Thompson N. Tetrahedron Lett. 2001, 42: 6417

<A NAME="RG18302ST-2J">2j</A> Hadden M. Nieuwenhuyzen M. Potts D. Stevenson PJ. Thompson N. Tetrahedron 2001, 57: 5615

<A NAME="RG18302ST-2K">2k</A> Ma D. Xia C. Jiang J. Org. Lett. 2001, 3: 2189

<A NAME="RG18302ST-2L">2l</A> Snider BB. Ahn Y. O’Hare SM. Org. Lett. 2001, 3: 4217

<A NAME="RG18302ST-2M">2m</A> He Y. Mahmud H. Wayland BR. Rasika Dias HV. Lovely CJ. Tetrahedron Lett. 2002, 43: 1171

For the chemistry of α-aminonitriles see:

<A NAME="RG18302ST-3A">3a</A> Enders D. Shilvock JP. Chem. Soc. Rev. 2000, 29: 359

<A NAME="RG18302ST-3B">3b</A> Husson H.-P. Royer J. Chem. Soc. Rev. 1999, 28: 383

<A NAME="RG18302ST-4">4</A> Polniaszek RP. Belmont SE. J. Org. Chem. 1991, 56: 4868

<A NAME="RG18302ST-5">5</A> Malassene R. Toupet L. Hurvois JP. Moinet C. Synlett 2002, 895

<A NAME="RG18302ST-6A">6a</A> Beifuss U. Ledderhose S. J. Chem. Soc., Chem. Commun. 1995, 2137

<A NAME="RG18302ST-6B">6b</A> Katritzky AR. Rachwald S. Rachwald B. Tetrahedron 1996, 52: 15031 ; and references cited therein

<A NAME="RG18302ST-6C">6c</A> Katritzky AR. Nichols DA. Qi M. Yang B. J. Heterocycl. Chem. 1997, 34: 1259

<A NAME="RG18302ST-7">7</A> Quintard JP. Elissondo B. Jousseaume B. Synthesis 1984, 495

<A NAME="RG18302ST-8">8</A> Schneider HJ. Junker A. Chem. Ber. 1986, 119: 2815

<A NAME="RG18302ST-9A">9a</A> Tamminen T. Jokela R. Tirkonnen B. Lounasmaa M. Tetrahedron 1989, 45: 2683

<A NAME="RG18302ST-9B">9b</A> Grierson DS. Harris M. Husson H.-P. Tetrahedron 1983, 39: 3683

<A NAME="RG18302ST-10A">10a</A> Posson H. Hurvois JP. Moinet C. Synlett 2000, 209

<A NAME="RG18302ST-10B">10b</A> For aza-Diels-Alder reactions in aqueous media see: Larsen SD. Grieco PA. J. Am. Chem. Soc. 1985, 107: 1768

<A NAME="RG18302ST-10C">10c</A> Grieco PA. Bahsas A. Tetrahedron Lett. 1988, 29: 5855

<A NAME="RG18302ST-10D">10d</A> Waldman H. Angew. Chem., Int. Ed. Engl. 1988, 2: 274

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.

<A NAME="RG18302ST-12A">12a</A> Katritzky AR. Rachwald S. Rachwald B. J. Org. Chem. 1995, 60: 2588

<A NAME="RG18302ST-12B">12b</A> Zhang J. Li CJ. J. Org. Chem. 2002, 67: 3969

<A NAME="RG18302ST-13">13</A> Kraus GA. Neuenschwander K. J. Org. Chem. 1981, 46: 4791

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]

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].

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).

<A NAME="RG18302ST-17A">17a</A> Stevens RV. Acc. Chem. Res. 1984, 17: 289

<A NAME="RG18302ST-17B">17b</A> Stevens RV. Lee AWM. J. Am. Chem. Soc. 1979, 101: 7032

<A NAME="RG18302ST-17C">17c</A> Deslongchamps P. In Stereoelectronic Effects in Organic Chemistry Baldwin J. Pergamon Press; Oxford: 1983.