One-pot Sequence for the Decarboxylation of α-Amino Acids

Abstract

Treatment of an α-amino acid with N-bromosuccinimide in water at pH 5 or in an alcoholic-aqueous ammonium chloride mixture, followed by addition of nickel(II) chloride and sodium borohydride, effected an overall decarboxylation via an intermediate nitrile to afford the corresponding amine in good yield.

α-amino acid - nitrile - amine - decarboxylation

References

1 Curtius T. Lederer A. Chem. Ber.  1886,  19:  2462 

See for example:

2a Pasini A. Zunio F. Angew. Chem., Int. Ed. Engl.  1987,  26:  615 

2b Miyadera T. Sugimura Y. Hashimoto T. Tanaka T. Iino K. Shibata T. Sugawara S. J. Antibiotics  1983,  36:  1034 

3 See for example: Martens J. Top. Curr. Chem.  1984,  125:  165 

4 Chatelus G. Bull. Soc. Chim. Fr.  1964,  2533 

5a Hashimoto M. Eda Y. Osanai Y. Iwai T. Aoki S. Chem. Lett.  1986,  6:  893 

5b Wallbaum S. Mehler T. Martens J. Synth. Commun.  1994,  24:  1381 

6a Boeker EA. Snell EE. In The Enzymes   3rd ed. Vol. 6:  Boyer PD. Academic Press; New York: 1972.  p.217-254  

6b Werle E. Angew. Chem.  1951,  63:  550 

6c Gale EF. Adv. Enzymol.  1946,  6:  1 

7a Nakai H. Kanaoka Y. Synthesis  1982,  141 

7b Flemming K. Strahlentherapie  1964,  123:  457 

7c Photochemical decarboxylation of N-arenesulfonyl amino acids: Papageorgiou G. Corrie JET. Tetrahedron  1999,  237 

8 Kametani T. Takano S. Hibino S. Takeshita M. Synthesis  1972,  475 

9a Rossen K. Simpson PM. Wells K. Synth. Commun.  1993,  23:  1071 

9b Kanao S. Shinozuka S. J. Pharm. Soc. Jpn.  1947,  67:  218 

10 Laval G. Clegg W. Crane CG. Hammershøi A. Sargeson AM. Golding BT. Chem. Commun.  2002,  1874 

11a Gowda BT. Mahadevappa DS. J. Chem. Soc., Perkin Trans. 2  1983,  323 

11b For the oxidative decarboxylation of N-protected amino acids see for example: Boto A. Hernandez R. De Leon Y. Suarez E. J. Org. Chem.  2001,  66:  7796 

12 Gopalakrishnan G. Hogg JL. J. Org. Chem.  1985,  50:  1206 

13 Satoh T. Suzuki S. Tetrahedron Lett.  1969,  4555 

Typical Procedures.

14a

l-Asparagine (2.90 g, 19.3 mmol) was taken up in a pH 5 phosphate buffer (prepared from 100 mL of a 0.1 M solution of citric acid and 100 mL of a 0.2 M solution of disodium hydrogen orthophosphate dodecahydrate) (90 mL). To the stirred amino acid solution was added NBS (10.3 g, 57.9 mmol) in DMF (20 mL) at r.t., where upon CO₂ gas was evolved immediately. After 30 min, nickel(II) dichloride hexahydrate (22.9 g, 96.5 mmol) was dissolved into the reaction mixture and NaBH₄ (5.84 g, 154 mmol) was added in portions with vigorous stirring. Addition of the latter was exothermic and hydrogen gas was vigorously evolved. After 20 min at r.t., the reaction mixture was filtered through Celite® and diluted with distilled H₂O (500 mL). The light green filtrate was loaded on a column (25 cm × 2 cm) of Dowex 50WX8-200 ion exchange resin, the column was washed well with H₂O (400 mL) and the amine was eluted with a concentration gradient of ammonium hydroxide. Removal of the solvent under reduced pressure afforded the amine, which was treated with 1.0 M HCl to give 3-aminopropionamide (12) as its hydrochloride (1.68 g, 13.5 mmol).

14b

l-Phenylalanine (400 mg, 2.42 mmol) was taken up in a mixture of EtOH (40 mL), H₂O (2 mL) and a sat. aq solution of NH₄Cl (1.5 mL). To the stirred amino acid solution was added NBS (1.07 g, 6.05 mmol) in DMF (5 mL) at r.t., whereupon CO₂ was evolved immediately. After 20 min, nickel(II) dichloride hexahydrate (2.30 g, 9.68 mmol) was dissolved into the reaction mixture and NaBH₄ (915 mg, 24.2 mmol) was added in portions with vigorous stirring. Addition of the latter was exothermic and hydrogen was vigorously evolved. After 30 min at r.t., the reaction was filtered through Celite®, and the ethanol was removed. The liquid residue was taken up in water (20 mL) and basified to pH 10 with aq 1.0 M NaOH. The aq solution was extracted with Et₂O (2 × 30 mL). The combined organic extracts were washed with a sat. aq solution of NaHCO₃ (20 mL) and dried over MgSO₄. Removal of the solvent afforded 2-phenylethylamine (9a) (208 mg, 71%) as a colourless oil.

15 Amino alcohol 15 is a building block for the synthesis of the antidepressant fluoxetine: Hilborn JW. Lu Z.-H. Jurgens AR. Fang QK. Byers P. Wald SA. Senanayake CH. Tetrahedron Lett.  2001,  8919