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Synlett 2004(1): 137-139  
DOI: 10.1055/s-2003-43371
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 2-Monosubstituted Pyrroles by Intramolecular Addition of Amines via Reductive Amination with Dibutyliodotin Hydride Complex (Bu2SnIH-HMPA)

Ikuya Shibata, Hirofumi Kato, Nobuaki Kanazawa, Makoto Yasuda, Akio Baba*
Department of Molecular Chemistry, Science and Technology Center of Molecules, Atoms and Ions Control, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Fax: +81(6)68797387; e-Mail: shibata@chem.eng.osaka-u.ac.jp;
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Publication History

Received 22 October 2003
Publication Date:
04 December 2003 (online)

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Abstract

Various 2-monosubstituted pyrroles were prepared in a one-pot procedure via the reductive amination of formyl groups of multifunctional substrates 1 by using Bu2SnIH-HMPA system.

Key words

pyrroles - reductive amination - tin hydride - complex

    References

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7

Typical Experimental Procedure (see Table [1] , entry 3).
To a dry nitrogen-filled 10 mL round-bottomed flask containing di-n-butyltin dihydride (Bu2SnH2, 0.166 g, 0.5 mmol) in 1,4-dioxane (1 mL) was added di-n-butyltin diiodide (Bu2SnI2, 0.243 g, 0.5 mmol) and HMPA (0.180 g, 1 mmol) at r.t. After stirring at r.t. for 10 min, the resulting solution of di-n-butyliodotin hydride (Bu2SnIH, 1 mmol) was cooled to 0 °C. Carbonyl substrate(1a) (0.196 g, 1 mmol), and p-chloroaniline (0.128 g) were added successively, and stirring was continued at 0 ºC for 2 h. The IR absorption band of Sn-H (1850 cm-1) disappeared, which indicated the formation of stannylamide (II). The mixture was heated to 80 ºC and stirred for 2 h. The reaction was quenched with MeOH (0.5 mL), and the residue was chromatographed on silica-gel column [FL100-DX (Fuji silysia)]. Elution with hexane gave pyrrole 2a (0.234 g, 81%).
Spectral data of representative products are as follows.
Compound 2a. IR: 1596, 1496 cm-1. 1H NMR (CDCl3): δ = 0.86 (t, J = 6.83 Hz, 3 H), 1.21-1.30 (m, 10 H), 1.44-1.55 (m, 2 H), 2.49 (t, J = 7.81 Hz, 2 H), 6.04-6.06 (m, 1 H), 6.21 (t, J = 2.93 Hz, 1 H), 6.67-6.69 (m, 1 H), 7.22 (d, J = 8.79 Hz, 2 H), 7.39 (d, J = 8.79 Hz, 2 H). 13C NMR (CDCl3): δ = 14.08, 22.63, 26.65, 29.13, 29.27, 29.30, 31.57, 31.80, 107.10, 108.26, 121.30, 127.30, 129.18, 132.77, 134.21, 139.06. HRMS: calcd for C18H24NCl: 289.1597. Found: 289.1597.
Compound 2e. IR: 1496 cm-1. 1H NMR (CDCl3): δ = 1.75-1.87 (m, 2 H), 2.51-2.59 (m, 4 H), 6.06-6.09 (m, 1 H), 6.18-6.21 (m, 1 H), 6.66-6.68 (m, 1 H), 7.05-7.35 (m, 9 H). 13C NMR (CDCl3): δ = 26.09, 30.67, 35.29, 107.39, 108.32, 121.46, 125.71, 127.19, 128.25, 128.31, 129.20, 132.76, 133.49, 138.87, 141.86. HRMS: calcd for C19H18NCl: 295.1128. Found: 295.1125.
Compound 2f. IR: 1600, 1492 cm-1. 1H NMR (CDCl3): δ = 6.35-6.38 (m, 1 H), 6.42-6.44 (m, 1 H), 6.90-6.91 (m, 1 H), 7.09 (d, J = 8.40 Hz, 2 H), 7.13-7.24 (m, 5 H), 7.28 (d, J = 8.40 Hz, 2 H). 13C NMR (CDCl3): δ = 109.60, 110.99, 124.16, 126.49, 126.76, 128.18, 128.32, 129.13, 132.19, 132.59, 133.79, 139.01. HRMS: calcd for C16H12NCl: 253.0658. Found: 253.0653.

10

It seems that chlorodibutyltin amide moiety (Bu2ClSnN-) does not has enough nucleophilicity to cause cyclization because of the electron withdrawing character of Cl-substituent (entry 4).