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

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

• 1 Wuts PGM. Greene TW. Protective Groups in Organic Synthesis   4th ed.:  Wiley; New York: 2007.  Chap. 7.
• 2 Ravinder K. Reddy AV. Mahesh KC. Narasimhulu M. Venkateswarlu Y. Synth. Commun.  2007,  37:  281 ; and references cited therein
• 3a Grehn L. Ragnarsson U. Angew. Chem., Int. Ed. Engl.  1984,  23:  296 
• 3b Franzen H. Grehn L. Ragnarsson U. J. Chem. Soc., Chem. Commun.  1984,  1699 
• 3c Ragnarsson U. Grehn L. Acc. Chem. Res.  1998,  31:  494 
• For recent examples using this protocol for the N-tert-butoxycarbonylation of indoles, see:
• 3d Baran PS. Shenvi RA. Mitsos CA. Angew. Chem. Int. Ed.  2005,  44:  3714 
• 3e Roy S. Gribble GW. Synth. Commun.  2006,  36:  3487 
• 3f Pedras MSC. Zheng Q.-A. Sarwar MG. Org. Biomol. Chem.  2007,  5:  1167 
• 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 
• 4b NaH + BocOC₆H₅: Dhanak D. Reese CB. J. Chem. Soc., Perkin Trans. 1  1986,  2181 
• 5a Sweet DV. Registry of Toxic Effects of Chemical Substances 1985-86   U. S. Govt. Printing Office; Washington D. C.: 1988.  p.3336 
• 5b Sweet DV. Registry of Toxic Effects of Chemical Substances 1985-86   U. S. Govt. Printing Office; Washington DC: 1988.  p.4049 
• 8 CsF-promoted desilylation of tert-butyldimethylsilyl ethers was reported: Cirillo PF. Panek JS. J. Org. Chem.  1990,  55:  6071 

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.