tert-Butyloxycarbonyl protecting group

Tert-butyloxycarbonyl protecting group

The tert-butyloxycarbonyl protecting group (BOC group) is a protecting group used in organic synthesis.

The BOC group can be added to the amine under aqueous conditions using di-tert-butyl dicarbonate in the presence of a base such as sodium bicarbonate. Protection of the amine can also be accomplished in acetonitrile solution using 4-dimethylaminopyridine (DMAP) as the base.

Removal of the BOC in amino acids can be accomplished with strong acids such as trifluoroacetic acid neat or in dichloromethane, or with HCl in methanol.[1][2][3] A complication may be the tendency of the t-butyl cation intermediate to alkylate other nucleophiles; scavengers such as anisole or thioanisole may be used.[4][5] Selective cleavage of the N-Boc group in the presence of other protecting groups is possible when using AlCl3.

Trimethylsilyl iodide followed by methanol can also be used for Boc deprotection,[6][7] especially where other deprotection methods are too harsh for the substrate.[8] The mechanism involves silylation of the carbonyl oxygen and elimination of tert-butyl iodide (1), methanolysis of the silyl ester to the carbamic acid (2) and finally decarboxylation to the amine (3).[9]

(1) R2NCO2tBu + Me3SiI → R2NCO2SiMe3 + tBuI
(2) R2NCO2SiMe3 + MeOH → R2NCO2H + MeOSiMe3
(3) R2NCO2H → R2NH + CO2

References

  1. ↑ R. M. Williams, P. J. Sinclair, D. E. DeMong, D. Chen, and D. Zhai (2003). "4-Morpholinecarboxylic acid, 6-oxo-2,3-diphenyl-, 1,1-dimethylethyl ester, (2S,3R)-". Org. Synth. 80: 18.
  2. ↑ E. A. Englund, H. N. Gopi, D. H. Appella (2004). "An Efficient Synthesis of a Probe for Protein Function: 2,3-Diaminopropionic Acid with Orthogonal Protecting Groups". Org. Lett. 6 (2): 213–215. doi:10.1021/ol0361599. PMID 14723531.
  3. ↑ D. M. Shendage, R. Fröhlich, G. Haufe (2004). "Highly Efficient Stereoconservative Amidation and Deamidation of α-Amino Acids". Org. Lett. 6 (21): 3675–3678. doi:10.1021/ol048771l. PMID 15469321.
  4. ↑ Lundt, Behrend F.; Johansen, Nils L.; Vølund, Aage; Markussen, Jan (1978). "Removal of t-Butyl and t-Butoxycarbonyl Protecting Groups with Trifluoroacetic acid". International Journal of Peptide and Protein Research 12 (5): 258–268. doi:10.1111/j.1399-3011.1978.tb02896.x. PMID 744685.
  5. ↑ Andrew B. Hughes. "1. Protection Reactions". In Vommina V. Sureshbabu, Narasimhamurthy Narendra. Amino Acids, Peptides and Proteins in Organic Chemistry: Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis 4. doi:10.1002/9783527631827.ch1.
  6. ↑ Richard S. Lott, Virander S. Chauhan, Charles H. Stammer (1979). "Trimethylsilyl iodide as a peptide deblocking agent". J. Chem. Soc., Chem. Commun.: 495–496. doi:10.1039/C39790000495.
  7. ↑ Olah, G; Narang, S. C. (1982). "Iodotrimethylsilane—a versatile synthetic reagent". Tetrahedron 38 (15): 2225. doi:10.1016/0040-4020(82)87002-6.
  8. ↑ Zhijian Liu, Nobuyoshi Yasuda, Michael Simeone, Robert A. Reamer (2014). "N-Boc Deprotection and Isolation Method for Water-Soluble Zwitterionic Compounds". J. Org. Chem. 79: 11792–11796. doi:10.1021/jo502319z.
  9. ↑ Michael E. Jung, Mark A. Lyster (1978). "Conversion of alkyl carbamates into amines via treatment with trimethylsilyl iodide". J. Chem. Soc., Chem. Commun.: 315–316. doi:10.1039/C39780000315.
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