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Synlett 2010(2): 203-206  
DOI: 10.1055/s-0029-1218569
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Takashi Okitsua, Daisuke Nakazawaa, Akihiro Kobayashia, Masahiro Mizohataa, Yasuko Inb, Toshimasa Ishidab, 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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Publication History

Received 15 October 2009
Publication Date:
11 December 2009 (online)

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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

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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.