Synthesis of 2,3-Dialkylindoles from 2-Alkenylphenylisocyanides and Imines by Silyltelluride- and Tin Hydride-Mediated Sequential Radical Reactions

Masashi Kotani; Shigeru Yamago; Ayumu Satoh; Hidetoshi Tokuyama; Tohru Fukuyama

doi:10.1055/s-2005-871931

LETTER

Synthesis of 2,3-Dialkylindoles from 2-Alkenylphenylisocyanides and Imines by Silyltelluride- and Tin Hydride-Mediated Sequential Radical Reactions

Masashi Kotani^a, Shigeru Yamago*^a,c, Ayumu Satoh^b, Hidetoshi Tokuyama*^b,d, Tohru Fukuyama^b
^a Division of Molecular Materials Science, Graduate School of Science, Osaka City University, Osaka 558-8585, Japan
^b Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo 113-0033, Japan
^c PRESTO, Japan Science and Technology Agency, Osaka City University, Osaka 558-8585, Japan
^d PRESTO, Japan Science and Technology Agency, The University of Tokyo, Tokyo 113-0033, Japan
e-Mail: yamago@sci.osaka-cu.ac.jp; e-Mail: tokuyama@mol.f.u-tokyo.ac.jp;

Abstract

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Abstract

A new method for the synthesis of 2,3-dialkylindoles is described. The silyltelluride-mediated coupling reaction of imines and 2-alkenylphenylisocyanides selectively occurred at the isocyanide moiety to give the corresponding imidoyltelluride. Tin hydride-mediated intramolecular cyclization of the imidoyltelluride affords 2,3-dialkylindoles in good to excellent combined yields.

Key words

indoles - radical reactions - cyclization - isocyanides - tellurium

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Typical Experimental Procedures.
To a solution of isocyanide 1A (188 mg, 1.0 mmol) and imine 4a (389 mg, 2.0 mmol) in MeCN (1 mL) was added silyltelluride 5 (739 mg, 2.0 mmol) under nitrogen atmosphere, and the resulting solution was stirred at 60 °C for 10 h. Solvent was removed under reduced pressure followed by purification by silica gel column chromatography to give imidoyltelluride 6Aa-ii in 96% yield (562 mg, 0.96 mmol). ¹H NMR (600 MHz, CDCl₃): δ = 2.68 (br s, 1 H), 3.77 (s, 3 H), 3.96 (d, J = 13.2 Hz, 1 H), 4.06 (d, J = 13.2 Hz, 1 H), 4.59 (s, 1 H), 6.33 (d, J = 16.1 Hz, 1 H), 6.82 (d, J = 7.8 Hz, 2 H), 6.95 (t, J = 7.5 Hz, 2 H), 7.09 (t, J = 7.4 Hz, 1 H), 7.17-7.20 (m, 3 H), 7.27-7.31 (m, 4 H), 7.34-7.37 (m, 4 H), 7.43 (t, J = 7.3 Hz, 2 H), 7.44 (d, J = 8.0 Hz, 2 H), 7.79 (d, J = 16.0 Hz, 1 H). ¹³C NMR (150 MHz, CDCl₃): δ = 51.61, 52.15, 70.15, 112.84, 118.58, 118.76, 124.42, 125.29, 127.11, 127.71 (two peaks), 128.01, 128.38 (two peaks), 128.47, 128.59, 129.05, 130.82, 138.84, 139.72, 140.70, 141.37, 151.46, 167.26. HRMS (FAB): m/z calcd for C₃₁H₂₉O₂N₂ ¹³⁰Te (M)⁺: 591.1247; found: 591.1294. A solution of imidoyltelluride 6Aa-ii (59 mg, 0.10 mmol) and AIBN (3.3 mg, 0.02 mmol) tributyltin hydride (32 mg, 0.12 mmol) in benzene (2 mL) was heated to 80 °C with stirring under nitrogen atmosphere for 1 h. Solvent was removed under reduced pressure followed by purification by silica gel column chromatography and GPC to give indole 7Aa in 87% yield (23 mg, 0.060 mmol). ¹H NMR (600 MHz, CDCl₃): δ = 1.72 (br s, 1 H), 3.55 (s, 3 H), 3.68 (s, 2 H), 3.79 (s, 2 H), 5.22 (s, 1 H), 7.09 (t, J = 7.5 Hz, 1 H), 7.15 (t, J = 7.5 Hz, 1 H), 7.24-7.35 (m, 9 H), 7.49 (d, J = 7.6 Hz, 2 H), 7.56 (d, J = 7.9 Hz, 1 H), 8.58 (br s, 1 H). ¹³C NMR (150 MHz, CDCl₃): δ = 30.09, 51.78, 52.01, 58.21, 105.06, 110.95, 118.55, 119.63, 121.91, 127.22, 127.30, 127.67, 128.17, 128.53, 128.57, 128.78, 134.93, 136.89, 139.75, 141.52, 172.13. HRMS (FAB): m/z calcd for C₂₅H₂₄O₂N₂ [M]⁺: 384.1838; found: 384.1832.