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Synlett 2013; 24(16): 2073-2076
DOI: 10.1055/s-0033-1339518
letter
© Georg Thieme Verlag Stuttgart · New York

A Formal Synthesis of (±)-Tylophorine Based on an Atom Transfer Radical Addition Reaction

Ever A. Blé-González
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Coyoacán, C.P. 04510, México, D.F., México   Fax: +52(55)56162203   eMail: acordero@unam.mx
,
Susana Porcel
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Coyoacán, C.P. 04510, México, D.F., México   Fax: +52(55)56162203   eMail: acordero@unam.mx
,
Alejandro Cordero-Vargas*
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Coyoacán, C.P. 04510, México, D.F., México   Fax: +52(55)56162203   eMail: acordero@unam.mx
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Publikationsverlauf

Received: 31. Mai 2013

Accepted after revision: 14. Juli 2013

Publikationsdatum:
21. August 2013 (online)

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Abstract

A short, formal synthesis of (±)-tylophorine was achieved using a radical–ionic sequence for the preparation of epoxides as the key step. This sequence, carried out between a phenantrenic allylic alcohol and iodoacetonitrile, provided an advanced intermediate containing most of the required elements for the final construction of the indolizidine scaffold.

Key words

tylophorine - total synthesis - free radicals - ATRA - epoxidation

Supporting Information

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

  • References and Notes

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  • 17 Synthesis of 11 from 10b To a solution of 10b (0.1 g, 0.2 mmol) on Et3N (0.04 mL, 0.4 mmol) in CH2Cl2 (5 mL) was added dropwise MsCl (0.03 mL, 0.4 mmol). The resulting mixture was stirred for 1 h at r.t. and then H2O was added. The reaction was extracted with CH2Cl2 (3 × 20 mL), the organic phase was dried with Na2SO4, and the solvent removed in vacuo. The product was used without purification for the next reaction. The crude was dissolved in DMF (1 mL) and transferred via cannula to a suspension of NaH (0.008g, 0.34 mmol, of 60% dispersion in mineral oil). The reaction mixture was stirred for 4 h at r.t. Then, H2O was added, and the reaction was extracted with Et2O (3 × 20 mL). The organic phase was dried with Na2SO4, and the solvent was removed in vacuo to yield the colorless solid 11. The product was purified by flash chromatography with hexane–EtOAc (9:1). All spectroscopic data for compound 11 fully matched with those reported by Fürstner.10 H NMR (400 MHz, CDCl3): δ = 1.26 (s, 9 H), 1.60–1.74 (m, 1 H), 1.75–1.90 (m, 2 H), 1.92–2.10 (m, 1 H), 2.55–2.65 (m 1 H), 3.27–3.37 (m, 1 H), 3.45–3.52 (m, 1 H), 3.90–3.97 (m, 1 H), 4.03 (s, 3 H), 4.11 (s, 3 H), 4.12 (s, 3 H), 4.21 (s, 3 H), 4.23–4.32 (m, 1 H), 7.17 (s, 1 H), 7.37 (s, 1 H), 7.79 (s, 1 H), 7.82 (br s, 1 H), 8.31 (br s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.7, 28.6, 29.7, 37.1, 46.8, 55.9, 56.0, 56.2, 56.7, 57.4, 79.0, 102.9, 106.8, 107.9, 123.9, 124.7, 125.2, 126.2, 126.3, 131.8, 148.7, 148.9, 149.0, 149.1, 154.7 ppm. MS (EI) m/z (%) = 481 (45) [M+], 311 (78), 170 (20), 114 (100), 70 (58), 57 (40). HRMS–FAB: m/z calcd for C28H35NO6 [M+]: 481.2464; found: 481.2459.