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Synlett 2006(7): 1075-1079  
DOI: 10.1055/s-2006-939073
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient and Green Access to Functionalized and Highly Constrained ­Heteropolycyclic Derivatives via a Microwave-Accelerated Diels-Alder ­Cycloaddition and Heterogeneous Hydrogenation Sequence

Krištof Kranjca, Marijan Kočevar*a, Florentina Iosifb, Simona M. Comanb, Vasile I. Parvulescu*b, Emilie Geninc, Jean-Pierre Genêtc, Véronique Michelet*c
a Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia
Fax: +386(1)2419220; e-Mail: marijan.kocevar@fkkt.uni-lj.si;
b University of Bucharest, Department of Chemical Technology and Catalysis, B-dul Regina Elisabeta 4-12, Bucharest 030016, Romania
Fax: +40(21)3320588; e-Mail: v-parvulescu@chem.unibuc.ro;
c Laboratoire de Synthèse Sélective Organique et Produits Naturels, ENSCP, UMR 7573, 11 rue P. et M. Curie, 75231 Paris Cedex 05, France
Fax: +33(1)44071062; e-Mail: veronique-michelet@enscp.fr;
Further Information

Publication History

Received 17 January 2006
Publication Date:
24 April 2006 (online)

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Abstract

This paper describes an efficient and green access to functionalized and highly constrained heteropolycyclic derivatives via a microwave-accelerated cycloaddition and heterogeneous ­hydrogenation sequence.

Key words

microwave - cycloadditions - hydrogenation - hetero­geneous catalysis - rhodium

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Microwave Irradiation Procedure: A mixture of 2H-pyran-2-one 1 (1 mmol) and N-substituted maleimide 2 (2.1 mmol) in distilled water (3 mL) was irradiated with microwaves (CEM Discover) for the time specified (final temperature 150 °C, power 100 W, ramp time 3 min). The temperature of the reaction was reduced to r.t.; the precipitated solid was filtered off and washed with water (0.5-1 mL). The anhydrous procedure was identical,
only no solvent was used.
N -[9-Acetyl-1,2,3,3a,4,4a,5,6,7,7a,8,8a-dodecahydro-8-methyl-1,3,5,7-tetraoxo-4,8-ethenobenzo[1,2- c :4,5- c ′]dipyrrol -4-yl]benzamide ( 3a). Mp > 358 °C (EtOH); IR (KBr): 1769, 1715, 1692, 1671, 1537 cm-1; 1H NMR (DMSO-d 6): δ = 1.86 (s, 3 H, Me), 2.15 (s, 3 H, COMe), 2.99 (d, 2 H, J = 8.3 Hz, 7a-H, 8a-H), 4.24 (d, 2 H, J = 8.3 Hz, 3a-H, 4a-H), 7.36 (s, 1 H, 10-H), 7.53 (m, 3 H, Ph), 7.89 (m, 2 H, Ph), 8.69 (s, 1 H, NHCOPh), 11.15 (s, 2 H, 2 × NH); 13C NMR (DMSO-d 6): δ = 18.1, 27.7, 41.0, 44.1, 50.3, 57.6, 127.5, 128.1, 131.1, 135.3, 138.8, 142.5, 167.4, 175.7, 177.0, 196.2; MS: m/z (%) = 421 (M+, 5), 105 (100); HRMS: m/z calcd for C22H19N3O6: 421.1273; found: 421.1262; Anal. Calcd for C22H19N3O6·0.8H2O: C, 60.63; H, 4.76; N, 9.64. Found: C, 60.74; H, 4.84; N, 9.29.
N -[8-Acetyl-1,2,3,3a,4,4a,5,6,7,7a,8,8a-dodecahydro-2,6,8-trimethyl-1,3,5,7-tetraoxo-4,8-ethenobenzo[1,2- c : 4,5- c ′]dipyrrol -4-yl]benzamide ( 3b). Mp 294-296 °C (EtOH); IR (KBr): 1767, 1697, 1679, 1661, 1540 cm-1; 1H NMR (DMSO-d 6): δ = 1.90 (s, 3 H, Me), 2.08 (s, 3 H, COMe), 2.69 (s, 6 H, 2 × Me), 3.11 (d, 2 H, J = 8.2 Hz, 7a-H, 8a-H), 4.31 (d, 2 H, J = 8.2 Hz, 3a-H, 4a-H), 7.20 (s, 1 H, 10-H), 7.56 (m, 3 H, Ph), 7.91 (m, 2 H, Ph), 8.75 (s, 1 H, NH); 13C NMR (DMSO-d 6): δ = 18.2, 24.3, 27.9, 41.2, 43.0, 49.0, 57.7, 127.5, 128.1, 131.2, 135.3, 138.1, 142.4, 167.7, 174.3, 175.5, 196.3; MS: m/z (%) = 449 (M+, 15), 105 (100); Anal. Calcd for C24H23N3O6·EtOH: C, 63.02; H, 5.90; N, 8.48. Found: C, 62.66; H, 5.55; N, 8.68.

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The Rh precursor [Rh(cod)Cl]2 (0.25 mmol metal) and TPPTS or m-TPPTC ligand (1 mmol) were dissolved in deionized water (50 mL) and stirred for 12 h. After stirring, LDH (0.5 g) was added to the solution, and the resulting solution was stirred for 24 h. The solution was filtered, the solid was washed with deionized water, and dried under vacuum at r.t. The catalysts structures and the chemical composition were confirmed by XRD analysis and XPS spectroscopy.

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Catalyst Tests; General Procedure. The tests were performed in a stirred stainless-steel autoclave using H2 pressures in the range 20-40 atm, catalyst (30 mg), and substrate 3 (30 mg) at different temperatures. All experiments were carried out in EtOAc. The reaction products were analyzed on a Knauer HPLC equipped with a chiral column EC 150/4 RESOLVOSIL BSA-7, UV-VIS detectors [MeCN-H3PO4 (0.1%), 1:3].
N -[9-Acetyl-1,2,3,3a,4,4a,5,6,7,7a,8,8a-dodecahydro-8-methyl-1,3,5,7-tetraoxo-4,8-ethanobenzo[1,2- c :4,5- c ′]dipyrrol -4-yl]benzamide ( 4a). 1H NMR (DMSO-d 6): δ = 1.66 (s, 3 H, Me), 1.90 (s, 3 H, COMe), 2.14 (d, 2 H, J = 6.4 Hz, 10-H), 2.42 (t, 1 H, J = 6.4 Hz, 9-H) 2.90 (d, 2 H, J = 8.1 Hz, 7a-H, 8a-H), 4.15 (d, 2 H, J = 8.1 Hz, 3a-H, 4a-H), 7.55 (m, 3 H, Ph), 7.90 (m, 2 H, Ph), 8.50 (s, 1 H, NHCOPh), 11.10 (s, 2 H, 2 × NH); 13C NMR (DMSO-d 6): δ = 18.0, 27.2, 32.4, 41.0, 41.8, 43.9, 49.7, 57.3, 127.6, 128.1, 131.3, 135.6, 167.9, 174.2, 175.6, 192.1; Anal. Calcd for C22H21N3O6: C, 62.41; H, 5.00; N, 9.92. Found: C, 62.53; H, 4.94; N, 9.90.
N -[9-Acetyl-1,2,3,3a,4,4a,5,6,7,7a,8,8a-dodecahydro-2,6,8-trimethyl-1,3,5,7-tetraoxo-4,8-ethanobenzo[1,2- c :4,5- c ′]dipyrrol -4-yl]benzamide ( 4b). 1H NMR (DMSO-d 6): δ = 1.69 (s, 3 H, Me), 1.83 (s, 3 H, COMe), 2.09 (d, 2 H, J = 6.6 Hz, 10-H), 2.40 (t, 1 H, J = 6.6 Hz, 9-H) 2.75 (s, 6 H, 2 × Me), 2.98 (d, 2 H, J = 8.1 Hz, 7a-H, 8a-H), 4.22 (d, 2 H, J = 8.1 Hz, 3a-H, 4a-H), 7.57 (m, 3 H, Ph), 7.89 (m, 2 H, Ph), 8.53 (s, 1 H, NHCOPh); 13C NMR (DMSO-d 6): δ = 17.9, 24.2, 27.5, 32.9, 40.8, 41.5, 44.2, 48.5, 56.6, 127.4, 128.0, 131.3, 135.1, 167.0, 173.5, 175.1, 190.1. Anal. Calcd for C24H25N3O6: C, 63.85; H, 5.58; N, 9.31. Found: C, 63.50; H, 5.55; N, 9.08.
N -[1,2,3,3a,4,4a,5,6,7,7a,8,8a-dodecahydro-9-(1-hydroxyethyl)-2,6,8-trimethyl-1,3,5,7-tetraoxo-4,8-ethenobenzo[1,2- c :4,5- c ′]dipyrrol -4-yl]benzamide ( 5b). 1H NMR (DMSO-d 6): δ = 1.23 (d, 3 H, J = 6.8 Hz, CH 3CHOH), 1.83 (s, 3 H, Me), 2.72 (s, 6 H, 2 × Me), 2.80 (s, 1 H, OH), 3.01 (d, 2 H, J = 8.1 Hz, 7a-H, 8a-H), 4.06 (q, 1 H, J = 6.8 Hz, CHOH), 4.29 (d, 2 H, J = 8.1 Hz, 3a-H, 4a-H), 6.71 (s, 1 H, 10-H), 7.55 (m, 3 H, Ph), 7.90 (m, 2 H, Ph), 8.74 (s, 1 H, NHCOPh); 13C NMR (DMSO-d 6): δ = 18.1, 24.1, 24.5, 40.9, 42.7, 50.1, 57.4, 74.6, 127.5, 128.1, 131.0, 135.2, 138.0, 143.7, 167.6, 174.8, 176.6. Anal. Calcd for C24H25N3O6: C, 63.85; H, 5.58; N, 9.31. Found: C, 64.04; H, 5.97; N, 9.68.