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Synlett 2002(11): 1803-1806
DOI: 10.1055/s-2002-34947
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Approach to some Novel 16-Methylated and 16-Halomethylated Tetrahydropyran and δ-Lactone Derivatives in both the Normal and the 13α-Estrone Series

Éva Frank, Erzsébet Mernyák, János Wölfling, Gyula Schneider*
Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary
Fax: +36(62)544200; e-Mail: schneider@chem.u-szeged.hu;
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Publication History

Received 11 July 2002
Publication Date:
21 October 2002 (online)

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Abstract

Intramolecular cyclizations of the 3-methyl ether of an unsaturated d-secoestrone alcohol and secoestrone carboxylic acid in both the normal and the 13α-estrone series are reported. The ring-closure reactions furnished substituted, new oxa-d-homoestrone derivatives stereoselectively.

Key words

cyclizations - etherification - esterification - diastereo­selectivity - estrone derivatives

11

General Procedure for the Synthesis of 16-Methyl Tetrahyropyrans: Compound 3 or 4 (300 mg, 1.00 mmol) was dissolved in CH2Cl2 (5 mL) and BF3·OEt2 (48% solution in Et2O, 0.47 mL, 1.5 mmol) was added drop wise during stirring of the mixture under reflux for 72 h. The solution was then diluted with water (10 mL) and extracted with CH2Cl2 (3 × 10 mL), and the combined organic phases were dried over Na2SO4. Evaporation in vacuo and purification by column chromatography (silica gel, CH2Cl2) afforded 5 (261 mg, 87%) or 9 (168 mg, 56%) and 10 (90 mg, 30%). 5: A colorless oil; Rf = 0.43 (CH2Cl2). 1H NMR (500 MHz, CDCl3): δ = 1.15 (s, 3 H, 18-H3), 1.16 (d, 3 H, J = 6.8 Hz, 16a-H3), 2.83 (m, 2 H, 6-H2), 3.15 (d, 1 H, J = 11.3 Hz, one of 17-H2), 3.54 (m, 1 H, 16α-H), 3.76 (s, 3 H, 3-OMe), 3.81 (d, 1 H, J = 11.3 Hz, the other17-H2), 6.63 (d, 1 H, J = 2.3 Hz, 4-H), 6.70 (dd, 1 H, J = 8.6 Hz, J = 2.3 Hz, 2-H) and 7.18 (d, 1 H, J = 8.6 Hz, 1-H). 13C NMR (125 MHz, CDCl3): δ = 22.1 (C-16a), 26.8, 27.3, 27.8 (C-18), 30.2, 30.7, 32.6 (C-13), 37.0, 37.6, 43.0, 45.0, 55.2 (3-OMe), 68.1 (C-16), 71.6 (C-17), 111.6 (C-2), 113.4 (C-4), 126.4 (C-1), 132.8 (C-10), 138.1 (C-5) and 157.6 (C-3). MS (EI): m/z (relative intensity) = 300 (M+, 100). - C20H28O2. 9: Mp 99-101 °C.
Rf = 0.47 (CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 0.98 (s, 3 H, 18-H3), 1.22 (d, 3 H, J = 6.0 Hz, 16a-H3), 2.84 (m, 2 H, 6-H2), 3.22 (d, 1 H, J = 10.6 Hz, one 17-H2), 3.46 (m, 1 H, 16α-H), 3.47 (d, 1 H, J = 10.6 Hz, the other 17-H2), 3.78 (s, 3 H, 3-OMe), 6.62 (d, 1 H, J = 2.4 Hz, 4-H), 6.72 (dd, 1 H, J = 8.6 Hz, J = 2.4 Hz, 2-H) and 7.21 (d, 1 H, J = 8.6 Hz, 1-H). 13C NMR (125 MHz, CDCl3): δ = 16.7 (C-18), 22.1 (C-16a), 25.6 (C-11), 25.7 (C-7), 30.0 (C-6), 32.3, 34.0 (C-13), 35.4, 38.6 (C-8), 43.8 (C-9), 47.7 (C-14), 55.2 (3-OMe), 74.9 (C-16), 80.0 (C-17), 111.6 (C-2), 113.6 (C-4), 126.1 (C-1), 132.8 (C-10), 137.9 (C-5), 157.5 (C-3). IR (KBr): 1080, 1238, 1502, 1606, 2864, 2922, 2940 cm-1. MS (EI): m/z (relative intensity) = 300 (M+, 100), 173(27). - C20H28O2. 10: A colorless oil. Rf = 0.42 (CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 1.02 (s, 3 H, 18-H3), 1.29 (d, 3 H, J = 6.9 Hz, 16a-H3), 2.84 (m, 2 H, 6-H2), 3.15 (d, 1 H, J = 11.0 Hz) and 3.40 (d, 1 H, J = 11.0 Hz, 17-H2), 3.78 (s, 3 H, 3-OMe), 4.30 (m, 1 H, 16β-H), 6.63 (d, 1 H, J = 2.5 Hz, 4-H), 6.72 (dd, 1 H, J = 8.6 Hz, J = 2.5 Hz, 2-H) and 7.21 (d, 1 H, J = 8.6 Hz, 1-H). 13C NMR (125 MHz, CDCl3): δ = 16.2 and 17.3
(C-16a and C-18), 25.6 (C-11), 25.8 (C-7), 28.6, 30.0, 34.5 (C-13), 35.8, 38.6 (C-8), 41.5 (C-9), 43.8 (C-14), 55.2 (3-OMe), 69.3 (C-16), 72.2 (C-17), 111.6 (C-2), 113.6 (C-4), 126.1 (C-1), 132.9 (C-10), 137.9 (C-5), 157.6 (C-3).
- C20H28O2. The compounds give correct elemental analyses.