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

doi:10.1055/s-2003-43371

LETTER

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;

Abstract

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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

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References

1 Shibata I. Moriuchi-Kawakami T. Tanizawa D. Suwa T. Sugiyama E. Matsuda H. Baba A. J. Org. Chem. 1998, 63: 383

2 Suwa T. Sugiyama E. Shibata I. Baba A. Synlett 2000, 556

3 For most recent work, see: Lee C.-F. Yang L.-M. Hwu T.-Y. Feng A.-S. Tseng J.-C. Luh T.-Y. J. Am. Chem. Soc. 2000, 122: 4992 ; and references therein

For a review see:

4a Gossauer A. In Pyrrole, Houben-Weyl, Methods in Organic Chemistry Vol. E6a/1: Thieme; Stuttgart: 1994. p.556

4b See also: Boger DL. Boyce CW. Labroli MA. Sehon CA. Jin Q. J. Am. Chem. Soc. 1999, 121: 54

4c Fürstner A. Weintritt H. J. Am. Chem. Soc. 1998, 120: 2817

4d See further: Sayah B. Pelloux-Leon N. Vallee Y. J. Org. Chem. 2000, 65: 2824

4e Liu J.-H. Yang Q.-C. Mak TCW. Wong HNC. J. Org. Chem. 2000, 65: 3587

For formation of the 2-monosubstituted pyrrole ring from γ-keto aldehydes or related precursors, see:

5a

Ref. [4a]

5b See also: Gadzhily RA. Fedoseev VM. Dzhafarov VG. Chem. Heterocycl. Compd. 1990, 26: 874

5c Engel N. Steglich W. Angew. Chem., Int. Ed. Engl. 1978, 17: 676

5d For syntheses of 2-monosubstituted pyrroles via acylation-reduction or alkylation of pyrrole see, for example: Garrido DOA. Buldain G. Frydman B. J. Org. Chem. 1984, 49: 2619

5e Muchowski JM. Solas DR. J. Org. Chem. 1984, 49: 203

5f See also: Kel’in AV. Sromek AW. Gevorgyan V. J. Am. Chem. Soc. 2001, 123: 2074

6 For preparation of 1, see: Kobayashi Y. Nakano M. Kumar GB. Kishihara K. J. Org. Chem. 1998, 63: 7505

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.

8 Kawakami T. Shibata I. Baba A. J. Org. Chem. 1996, 61: 82

We have already reported the increase of nucleophilicity of Sn-N bonds by pentacoordination, see:

9a Shibata I. Baba A. Iwasaki H. Matsuda H. J. Org. Chem. 1986, 51: 2177

9b Baba A. Kishiki H. Shibata I. Matsuda H. Organometallics 1984, 4: 1329

9c Shibata I. Baba A. Matsuda H. J. Chem. Soc., Chem. Commun. 1986, 1703

9d Shibata I. Nakamura K. Baba A. Matsuda H. Bull. Chem. Soc. Jpn. 1989, 62: 853

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).