ipso-Iodocyclization
of Ethoxyethyl Ethers to Alkynes at the ortho-Position: An
Efficient Synthesis of Functionalized Spiro Compounds

Takashi Okitsu; Daisuke Nakazawa; Akihiro Kobayashi; Masahiro Mizohata; Yasuko In; Toshimasa Ishida; Akimori Wada

doi:10.1055/s-0029-1218569

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Synlett 2010(2): 203-206
DOI: 10.1055/s-0029-1218569

LETTER

ipso-Iodocyclization of Ethoxyethyl Ethers to Alkynes at the ortho-Position: An Efficient Synthesis of Functionalized Spiro Compounds

Takashi Okitsu^a, Daisuke Nakazawa^a, Akihiro Kobayashi^a, Masahiro Mizohata^a, Yasuko In^b, Toshimasa Ishida^b, Akimori Wada*^a
^a Department of Organic Chemistry for Life Science, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi,Higashinada-ku, Kobe 658-8558, Japan
Fax: +81(78)4417562; e-Mail: a-wada@kobepharma-u.ac.jp;
^b Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan

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Publikationsverlauf

Received 15 October 2009
Publikationsdatum:
11. Dezember 2009 (online)

Abstract
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Abstract

An efficient approach to the synthesis of azaspiro compounds having dissymmetric dienone cores was achieved by ipso-iodocyclization of ethoxyethyl ether to alkynes. When the linker was an ether or an ester, domino iodocyclizaion/Diels-Alder reaction proceeded to afford the dimer, which can be transformed into the bridgehead-spiro connection ring system by a domino retro-Diels-Alder/Diels-Alder process.

Key words

iodocyclization - spiro compounds - heterocycles - domino reaction - Diels-Alder reaction

References and Notes

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General Procedure for ipso -Iodocyclization: To a solution of 1a (51.0 mg, 0.150 mmol) in anhydrous CH₂Cl₂ (1.5 mL) was added NIS (142 mg, 0.600 mmol) followed by BF₃˙OEt₂ (74 µL, 0.600 mmol) at -40 ˚C. When the reaction was complete, the mixture was diluted with sat. aq Na₂S₂O₃ and the mixture was extracted with CH₂Cl₂. The organic layer was dried over Na₂SO₄, filtered, and evaporated in vacuo. The residue was purified by flash column chromatography on silica gel (hexane-EtOAc = 1:1) to give 2a (52.8 mg, 89%). N-Acetyl-3-iodo-4-phenyl-1-azaspiro[4,5]deca-3,7,9-trien-6-one (2a): yellow amorphous solid. IR (CHCl₃): 3017, 1676, 1655 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.35-7.27 (3 H, m), 7.03-7.01 (2 H, m), 6.71 (ddd, J = 10.0, 4.5, 3.0 Hz, 1 H), 6.23-6.22 (m, 2 H), 6.01 (d, J = 9.5 Hz, 1 H), 4.78 (d, J = 13.5 Hz, 1 H), 4.61 (d, J = 13.5 Hz, 1 H), 2.12 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 197.2, 167.5, 145.9, 141.1, 138.9, 132.6, 128.9, 128.8, 128.0, 126.9, 123.5, 91.2, 77.7, 62.9, 21.8. HRMS (EI): m/z [M]⁺ calcd for C₁₇H₁₄INO₂: 391.0069; found: 391.0080.

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CCDC 731726 (2m) contains the supplementary crystallographic data for this paper. This data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.