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Synlett 2012; 23(9): 1349-1352
DOI: 10.1055/s-0031-1291047
letter
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of (–)-9-epi-Metazocine

Qiang Chen
a   State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912582   eMail: shexg@lzu.edu.cn
,
Xing Huo
a   State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912582   eMail: shexg@lzu.edu.cn
,
Huaiji Zheng
a   State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912582   eMail: shexg@lzu.edu.cn
,
Xuegong She*
a   State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912582   eMail: shexg@lzu.edu.cn
b   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
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Publikationsverlauf

Received: 08. März 2012

Accepted after revision: 28. März 2012

Publikationsdatum:
08. Mai 2012 (online)

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Abstract

(–)-9-epi-Metazocine was synthesized through an Evans syn aldol reaction, ring-closing metathesis reaction and intramolecular radical cyclization.

Key word

asymmetric - drug development - aldol - ring-closing ­metathesis - radical cyclization

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

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  • 21 Preparation of compound 18 (Scheme 4): To a solution of 3 (43 mg, 0.12 mmol) in benzene (10 mL) at reflux, was added dropwise a solution of Bu3SnH (51 mg, 0.18 mmol) and AIBN (30 mg, 0.18 mmol) in benzene (10 mL) over 1 h by using a syringe. The mixture was then heated at reflux for 3 h. After evaporation of the solvent, the residue was purified by chromatography on silica gel (hexane–EtOAc, 2:1) to give 18 (27 mg, 87%); [α] d 22 –77 (c 1.0, CHCl3); 1H NMR (CDCl3, 400 MHz): δ = 6.96 (d, J = 8.0 Hz, 1 H), 6.90 (d, J = 2.4 Hz, 1 H), 6.72 (dd, J = 2.4, 8.0 Hz, 1 H), 3.78 (s, 3 H), 3.53 (s, 1 H), 2.96 (s, 2 H), 2.93 (s, 3 H), 2.48 (d, J = 17.6 Hz, 1 H), 2.30 (d, J = 19.2 Hz, 1 H), 2.04 (q, J = 6.8 Hz, 1 H), 1.38 (s, 3 H), 1.19 (d, J = 7.2 Hz, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 169.0, 158.6, 145.3, 130.6, 123.7, 112.4, 111.5, 61.0, 55.3, 43.4, 36.9, 36.9, 34.2, 33.8, 24.1, 14.4; HRMS (ESI): m/z [M + H]+ calcd for C16H22NO2: 260.1645; found: 260.1657
  • 22 (–)-9-epi-metazocine (2b): [α] d 17 +22.0 (c 0.5, CHCl3); 1H NMR (CDCl3, 400 MHz): δ = 6.95 (d, J = 8.0 Hz, 1 H), 6.80 (d, J = 2.4 Hz, 1 H), 6.61 (dd, J = 2.4, 8.0 Hz, 1 H), 3.13 (d, J = 17.6 Hz, 1 H), 2.92 (d, J = 5.6 Hz, 1 H), 2.67 (dd, J = 5.6, 17.6 Hz, 1 H), 2.44 (d, J = 6.8 Hz, 1 H), 2.36 (s, 3 H), 2.03 (d, J = 8.4 Hz, 2 H), 1.88 (q, J = 6.8 Hz, 1 H), 1.29 (s, 3 H), 1.26 (d, J = 7.2 Hz, 3 H), 1.10 (d, J = 9.6 Hz, 1 H); 13C NMR (CDCl3, 100 MHz): δ = 154.1, 146.4, 129.1, 128.6, 113.0, 111.5, 60.1, 47.6, 43.0, 38.2, 34.9, 34.8, 27.3, 24.0, 15.0; IR: 3254, 2932, 2865, 1610, 1496, 1485, 1360, 769 cm–1; HRMS (ESI): m/z [M + H]+ calcd for C15H22NO: 232.1696; found: 232.1692