Synlett 2003(11): 1752-1754
DOI: 10.1055/s-2003-41438
LETTER
© Georg Thieme Verlag Stuttgart · New York

Transition Metal Complexes in Organic Synthesis, Part 69. [1] Total Synthesis of the Amaryllidaceae Alkaloids Anhydrolycorinone and Hippadine Using Iron- and Palladium-Mediated Coupling Reactions

Hans-Joachim Knölker*, Salima Filali
Institut für Organische Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany
Fax: +49(351)46337030; e-Mail: hans-joachim.knoelker@chemie.tu-dresden.de;
Further Information

Publication History

Received 30 June 2003
Publication Date:
22 September 2003 (online)

Abstract

A novel synthesis of the Amaryllidaceae alkaloids anhydrolycorinone and hippadine has been developed using an iron-mediated oxidative alkylamine cyclization and an intramolecular palladium-mediated biaryl coupling as the key steps.

14

All new compounds have been fully characterized (IR, 1H NMR, 13C NMR, MS, and elemental analysis or HRMS). 13C NMR and DEPT spectral data (125 MHz, CDCl3) of representative compounds. 17: δ = 30.75 (CH2), 35.90 (CH), 40.27 (CH2), 47.66 (CH2), 57.97 (CH2), 59.76 (CH), 66.57 (CH), 84.39 (CH), 85.53 (CH), 86.99 (C), 101.53 (CH2), 109.71 (CH), 118.46 (CH), 135.61 (C), 147.35 (C), 148.34 (C), 212.06 (3 CO). 5: δ = 34.64 (CH2), 43.22 (CH), 54.31 (CH2), 60.16 (CH), 60.85 (CH2), 63.78 (CH), 66.32 (CH), 85.85 (CH), 86.70 (CH), 87.25 (C), 101.53 (CH2), 110.19 (CH), 118.45 (CH), 135.01 (C), 147.36 (C), 148.44 (C), 211.75 (3 CO). 18: δ = 32.95 (CH2), 36.46 (CH), 49.25 (CH2), 59.56 (CH), 62.43 (CH2), 87.26 (C), 101.50 (CH2), 110.51 (CH), 118.25 (CH), 119.80 (CH), 122.92 (CH), 124.79 (CH), 130.31 (CH), 135.29 (C), 147.33 (C), 148.43 (C). Anhydrolycorinone (1): δ = 27.45 (CH2), 46.52 (CH2), 100.89 (CH), 102.05 (CH2), 106.83 (CH), 116.79 (C), 119.46 (CH), 123.10 (C), 123.27 (CH), 123.82 (CH), 130.66 (C), 130.87 (C), 139.39 (C), 148.43 (C), 151.85 (C), 159.52 (C=O). Hippadine (2): δ = 101.75 (CH), 102.29 (CH2), 108.05 (CH), 110.82 (CH), 116.71 (C), 118.38 (CH), 122.51 (C), 122.63 (CH), 123.55 (CH), 124.00 (CH), 128.42 (C), 130.97 (C), 131.66 (C), 148.54 (C), 152.60 (C), 158.19 (C=O).

15

Iron-mediated oxidative alkylamine cyclization of 17 to 5: Ferricenium hexafluorophosphate (291 mg, 0.88 mmol) and anhyd. Na2CO3 (374 mg, 3.53 mmol) were added to a solution of complex 17 (185 mg, 0.354 mmol) in degassed anhyd CH2Cl2 (15 mL) under an argon atmosphere. The resulting dark green suspension was stirred at r.t. for 3 d. During this time the color turned to orange (formation of ferrocene). The reaction mixture was filtered through a short path of Celite which was subsequently washed with CH2Cl2. Removal of the solvent from the combined filtrates and flash chromatography (hexane-EtOAc, 9:1) of the residue on silica gel provided complex 5 as light yellow crystals, yield: 158 mg (86%), mp 122 °C.