R. S. Navath et al. / Tetrahedron Letters 47 (2006) 389–393
393
5. Brosse, N.; Pinto, M.-F.; Gregoire, B. J. Tetrahedron Lett.
2000, 41, 205–207.
known to be hygroscopic and undergoes hydrolysis to
form water-insoluble bismuth oxychloride (BiOCl) and
HCl.19 This instability and reactivity of BiCl3 in the
presence of water might partially explain the need to
add fresh BiCl3 a second time after 1 h to improve the
conversion yield. But, attempts to mimic the result of
such hydrolysis by reducing the amount of BiCl3 used
and adding the expected amount of HCl failed to effect
the desired deprotection. Additional experiments are
necessary to fully understand the mechanistic aspects
of the reaction.
6. Stafford, J. A.; Brackeen, M. F.; Karanewsky, D. S.;
Valvano, N. L. Tetrahedron Lett. 1993, 34, 7873–7876.
7. Carpino, L. A. J. Org. Chem. 1964, 29, 2820–2824.
8. Allan, R. D.; Johnston, G. A.; Kazlauskas, R.; Tran, H.
W. J. Chem. Soc., Perkin Trans. 1 1983, 2983–2985.
9. Degerbeck, F.; Fransson, B.; Grehn, L.; Ragnarsson, U.
J. Chem. Soc., Perkin Trans. 1 1992, 245–253.
10. Lin, L. S.; Lanza, T.; Laszlo, S. E. d.; Truoung, Q.;
Kamenecka, T.; Hagmann, W. K. Tetrahedron Lett. 2000,
41, 7013–7016.
11. Strazzolini, P.; Melloni, T.; Glumanini, A. G. Tetrahedron
2001, 57, 9033–9043.
12. Green, T. W.; Wuts, P. G. M. In Protecting Groups in
Organic Synthesis, 3rd ed.; John Wiley & Sons: New York,
1999; pp 518–525, and 617–618.
13. Ramesh, K.; Yann, B.; Zohreh, S.; Karl, A. H.; William,
D. L. J. Org. Chem. 2004, 69, 6131–6133.
14. Yadav, J. S.; Reddy, B. V. S.; Reddy, K. S.; Reddy, K. B.
Tetrahedron Lett. 2002, 43, 1549–1551.
In summary, we developed a new procedure for the
deprotection of N-Boc that offers mild reaction condi-
tions, excellent yield, and high chemo-selectivity. The
deprotection procedure uses inexpensive catalyst
(BiCl3) and a simple experimental work-up procedure.
In addition, no alkylated side reactions of tryptophan,
methionine, and cysteine residues were observed. This
BiCl3-mediated N-Boc deprotection should find
general application in the synthesis of amino acids and
peptides.
15. Routier, S.; Sauge, L.; Ayerbe, N.; Coudert, G.; Merour,
J. Y. Tetrahedron Lett. 2002, 43, 589–591.
16. Atherton, E.; Sheppard, R. C. Solid Phase Peptide
Synthesis: A Practical Approach; IRL Press: Oxford, 1989.
17. Like other group 15 elements, bismuth has +3 and +5
oxidation states. In the +3 state, the two 6s electrons are
increasingly less available as one goes down from N to Bi.
Thus, Bi(III) derivatives are much less basic than other
E(III) derivatives in the same group.
Acknowledgements
We gratefully acknowledge the financial support of
grant GM62752 from the National Institutes of Health.
18. Le Roux, C.; Dubac, J. Synlett 2002, 181–200, and
references cited therein.
19. Briand, G. G.; Burford, N. Chem. Rev. 1999, 99, 2601–
2657.
References and notes
20. Swamy, N. R.; Venkateswarlu, Y. Tetrahedron Lett. 2002,
43, 7549–7552.
1. Jarowinski, K.; Kocienski, P. J. Chem. Soc., Perkin Trans.
1 2001, 2109–2135.
21. Swamy, N. R.; Gondaji, G.; Nagaiah, K. Synth. Commun.
2002, 32, 2307–2312.
2. Green, T. W.; Wuts, P. G. M. In Protecting Groups in
Organic Synthesis; John Wiley & Sons: New York, 1999;
pp 65–67, and 404–408.
3. Bodanszky, M.; Bodanszky, A. The Practice of Peptide
Synthesis, 2nd ed.; Springer: Berlin, Germany, 1994.
4. Connell, R. D.; Rein, T.; Akermark, B.; Helquist, P.
J. Org. Chem. 1988, 53, 3845–3849.
22. Swamy, N. R.; Venkateswarlu, Y. Synth. Commun. 2003,
33, 547–554.
23. Komatsu, N.; Uda, M.; Suzuki, H.; Takahashi, T.;
Domae, T.; Wada, M. Tetrahedron Lett. 1997, 38, 7215–
7218.
24. Swamy, N. R.; Venkateswarlu, Y. Synthesis 2002, 598–
600.