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Synlett 2008(2): 294-296  
DOI: 10.1055/s-2007-1000869
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient N-tert-Butoxycarbonylation of Indoles with Di-tert-butyl Dicarbonate Catalyzed by Cesium Fluoride

Nobuyuki Inahashi, Ayako Matsumiya, Tsuneo Sato*
Department of Life Science, Kurashiki University of Science and the Arts, Kurashiki 712-8505, Japan
Fax: +81(86)4401062; e-Mail: sato@chem.kusa.ac.jp;
Further Information

Publication History

Received 29 October 2007
Publication Date:
21 December 2007 (online)

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Abstract

An environmentally friendly process for the tert-butoxycarbonylation of indoles with di-tert-butyl dicarbonate has been developed. Catalytic amount of cesium fluoride can accelerate this tert-butoxycarbonylation.

Key words

catalysis - cesium fluoride - di-tert-butyl dicarbonate - indoles - protecting groups

    References and Notes

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  • For recent examples using this protocol for the N-tert-butoxycarbonylation of indoles, see:
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  • For other methods for the N-tert-butoxycarbonylation of indoles, see:
  • 4a NaH + BocN3: Hasan I. Marinelli ER. Lin L.-CC. Fowler FW. Levy AB. J. Org. Chem.  1981,  46:  157 
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6

CsF was the best catalyst among the cesium salts examined under the identical conditions: CsCl (0%), CsBr (6%), CsI (0%).

7

Typical Procedure (Table [2] , entry 1): Boc2O (284 mg, 1.3 mmol) was added dropwise to a stirred mixture of indole (117 mg, 1.0 mmol) and CsF9 (30 mg, 0.2 mmol) in DMF (1 mL) at r.t. The reaction was complete in 6 h at the same temperature. The reaction mixture was poured into H2O and extracted with EtOAc. The organic layer was dried (Na2SO4) and evaporated. Column chromatography of the residue on silica gel (7% EtOAc-hexane) afforded tert-butyl indole-1-carboxylate (202 mg, 93%).10

9

Purchased from Mitsuwa Chemicals Co., Ltd.

10

The selected spectroscopic data are shown as follows:
tert -Butyl 3-Formylindole-1-carboxylate: 1H NMR (CDCl3): δ = 1.71 (s, 9 H), 7.38 (t, J = 8.3 Hz, 1 H), 7.42 (t, J = 8.3 Hz, 1 H), 8.15 (d, J = 8.3 Hz, 1 H), 8.24 (s, 1 H), 8.29 (d, J = 8.3 Hz, 1 H), 10.11 (s, 1 H). 13C NMR (CDCl3): δ = 28.0, 85.6, 115.1, 121.5, 122.1, 124.6, 126.0, 126.1, 135.9, 136.4, 148.8, 185.7. tert -Butyl 7-Methylindole-1-carboxylate: 1H NMR (CDCl3): δ = 1.63 (s, 9 H), 2.64 (s, 3 H), 6.53 (d, J = 4.0 Hz, 1 H), 7.09 (d, J = 7.6 Hz, 1 H), 7.14 (t, J = 7.6 Hz, 1 H), 7.38 (d, J = 7.6 Hz, 1 H), 7.51 (d, J = 4.0 Hz, 1 H). 13C NMR (CDCl3): δ = 22.1, 28.0, 83.2, 107.3, 118.5, 123.1, 125.3, 127.5, 128.0, 131.9, 134.7, 149.5. tert -Butyl 3-[3-( tert -Butyldimethylsilanyloxy)butyl]indole-1-carboxylate: 1H NMR (CDCl3): δ = 0.08 (s, 3 H), 0.09 (s, 3 H), 0.92 (s, 9 H), 1.20 (d, J = 6.1 Hz, 3 H), 1.67 (s, 9 H), 1.76-1.89 (m, 2 H), 2.61-2.70 (m, 1 H), 2.75-2.82 (m, 1 H), 3.88-3.96 (m, 1 H), 7.23 (t, J = 7.9 Hz, 1 H), 7.30 (t, J = 7.9 Hz, 1 H), 7.34 (s, 1 H), 7.52 (d, J = 7.9 Hz, 1 H), 8.12 (br, 1 H). 13C NMR (CDCl3): δ = -4.7, -4.3, 18.1, 21.1, 23.8, 25.9, 28.2, 39.0, 68.2, 83.2, 115.2, 119.0, 121.2, 122.1, 122.2, 124.2, 130.7, 149.9. tert -Butyl 3-[2-Acetylamino-2-(methoxycarbonyl)ethyl]indole-1-carboxylate: 1H NMR (CDCl3): δ = 1.67 (s, 9 H), 1.98 (s, 3 H), 3.23 (dd, J = 5.2, 14.7 Hz, 1 H), 3.30 (dd, J = 5.5, 14.7 Hz, 1 H), 3.71 (s, 3 H), 4.95 (dt, J = 5.2, 7.7 Hz, 1 H), 6.02 (d, J = 7.7 Hz, 1 H), 7.23 (t, J = 7.6 Hz, 1 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.36 (s, 1 H), 7.47 (d, J = 7.6 Hz, 1 H), 8.11 (d, J = 7.6 Hz, 1 H). 13C NMR (CDCl3): δ = 22.7, 27.0, 27.9, 52.1, 52.3, 83.4, 114.9, 115.0, 118.5, 122.3, 123.7, 124.2, 130.3, 135.0, 149.3, 169.7, 172.0. tert -Butyl 3-(3-Hydroxybutyl) indole-1-carboxylate: 1H NMR (CDCl3): δ = 1.26 (d, J = 6.1 Hz, 3 H), 1.37 (br, 1 H), 1.67 (s, 9 H), 1.83-1.89 (m, 2 H), 2.72-2.80 (m, 1 H), 2.80-2.88 (m, 1 H), 3.91 (br s, 1 H), 7.23 (t, J = 7.6 Hz, 1 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.37 (s, 1 H), 7.54 (d, J = 7.6 Hz, 1 H), 8.12 (br, 1 H). 13C NMR (CDCl3): δ = 21.0, 23.5, 28.1, 38.4, 67.4, 83.2, 115.1, 118.9, 120.7, 122.2, 124.2, 130.6, 135.5, 149.7.