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LETTERS
SYNLETT
R.A.; Beckman, A.; Ostresh, J.M. Int. J. Pept. Protein Res. 1986,
27, 653. (c) HF / anisole: Yamashiro, D.; Blake, J.; Li, C.H.
J. Am. Chem. Soc. 1972, 94, 2855.
4.
5.
Wasserman, H.H.; Robinson, R.P.; Carter, C.G. J. Am. Chem. Soc.
1983, 105, 1697.
(a) SiCl / phenol: Sivanandaish, K.M.; Suresh Babu, V.V.;
4
Gangadhar, B.P. Tetrahedron Lett. 1996, 37, 5989.
(b) Ce(NH ) (NO ) / acetonitrile: Hwu, J.R.; Jain, M.T.; Tsay,
4 2
3 6
S-Ch.; Hakimelahi, G.H. Tetrahedron Lett. 1996, 37, 2035.
(c) Mg(ClO ) /acetonitrile: Stafford, J.A.; Brackeen, M.F.;
4 2
Karanewsky, D.S.; Valvano, N.L. Tetrahedron Lett. 1993, 34,
7873. (d) Mg(OMe) / methanol: Wei, Z-Y.; Knaus, E.E.
Tetrahedron Lett. 1994, 35, 847.
2
Scheme 2
6.
7.
8.
Rawal, V.H.; Cava, M.P. Tetrahedron Lett. 1985, 26, 6141.
Apelqvist, T.; Wensbo, D. Tetrahedron Lett. 1996, 37, 1471.
3 (77%). Control experiments shown, see Scheme 2, that conventional
heating methods are less convenient, in particular for the removal of
Boc protecting amino groups.
a) Ezquerra, J.; Rubio, A.; Martín, J.; García-Navío, J.L.
Tetrahedron: Asymmetry 1997, 8, 669. b) Diaz, A.; Siro, J.G.;
García-Navío, J.L.; Vaquero, J.J.; Alvarez-Builla, J. Synthesis
1997, 5, 559.
Chemoselective N-Boc amide removal was also observed in the
presence of OTBDPS ether group, as in the 2-pyrrolidone derivative
(see Table, entry 9). Finally, Boc groups attached to nitrogen atoms
belonging to an aromatic system could only be eliminated in the case of
an imidazole nucleus (see Table, entry 10). Decomposition products
were obtained for other aromatic N-Boc protected heterocycles, such as
pyrrole and indole.
9.
For reviews on microwaves in organic synthesis, see: (a) Giguere,
R.J. Organic Synthesis. Theory and Applications 1989, 1, 103.
(b) Mingos, M.P.; Baghrust, D.R. Chem. Soc. Rev. 1991, 20, 1.
(c) Bram, G.; Loupy, A.; Vilemin, D. in Solid Supports and
Catalysis in Organic Synthesis, Smith, K. Ed., Ellis Horwood,
New York, pp 302, 1992. (d) Caddick, S. Tetrahedron 1995, 51,
10403.
In summary, a mild, simple, short, and efficient method for the tert-
butoxycarbonyl deprotection of nitrogen atoms has been developed by
coupling silica and microwave irradiation which it is of particular
10. A commercial microwave oven with 900 watts of power output
was used. The power generated by the oven was measured before
every experiment by the method described by Watkins, K.W.
J. Chem. Ed. 1983, 60, 1043.
success
for amino groups. The potential for chemoselective
deprotection of different N-Boc groups has been demonstrated. The
removal of other protecting groups using this procedure is currently
under investigation.
11. In a typical experiment, N-Boc derivative (1 mmol) was dissolved
in CH Cl (50 mL) and silica gel (230-400 mesh) (10 g) was
2
2
added. The solvent was taken off on vacuo and the powdered solid
obtained was irradiated in the microwave oven, in an open
erlenmeyer flask for the time described (Table) at 450 watts. The
resulting solid was thoroughly washed with acetone or methanol,
and then isolated to afford pure products.
References and notes
1.
Kocienski, P.J. In Protecting Groups; George Thieme Verlag
Stuttgart. New York, 1994.
2.
3.
Sakai, N.; Ohfune, Y.J. J. Am. Chem. Soc.1992, 114, 998.
(a) HCl / ethyl acetate: Stahl, G.L.; Walter, R.; Smith, C.W.
J. Org. Chem. 1978, 43, 2285. (b) H SO / dioxane: Houghten,
2
4