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Alternate Names: di-t-butyl pyrocarbonate; Boc anhydride; Boc2O.
Physical Data: mp 22-24 °C; bp 56-57 °C/0.5 mm Hg; fp 37 °C; d 0.950 g cm-3; nD20 1.4103.
Solubility: insol cold H2O; sol most organic solvents such as decalin, toluene, CCl4, THF, dioxane, alcohols, acetone, MeCN, DMF.
Analysis of Reagent Purity: IR 1810 and 1765 cm-1; NMR 1.50 (CCl4).
Handling, Storage, and Precautions: the liquid is flammable and must be stored in a refrigerator in the absence of moisture. Do not heat above 80 °C.
The substitution of a secondary amino group in the presence of a primary amine has been performed by an indirect route: formation of the labile Schiff base of the primary amine and then t-butoxycarbonylation of the secondary nitrogen (eq 7).30 Selective protection of polyamines may also be achieved by an indirect route in the presence of DMAP (see below).
At pH 10.3, hydroxylamine itself gives the O-substituted product,12 whereas treatment of N-alkylhydroxylamines in dioxane furnishes the N-Boc derivatives (eq 12).43 The O-Boc hydroxylamine12,44 as well as O-Boc oximes45 are themselves efficient t-butoxycarbonylating agents.
N-Benzyloxycarbonyl (Cbz) and 9-fluorenylmethyloxycarbonyl (Fmoc) amino protecting groups are also widely used in peptide synthesis.2 The choice of protecting groups, and hence of the conditions for their cleavage (Cbz: hydrogenolysis or HBr/HOAc; Fmoc: piperidine or F-)1 plays a key role in the planning of a synthesis. For instance, orthogonal protection (Boc/Cbz or Fmoc/Boc or Cbz) is of crucial importance in the case of the trifunctional amino acids. For a given peptide segment, chemoselective transformation of an amino protecting group into another one under neutral conditions may be very useful for the synthesis.
t-Butoxycarbonylation of Phenols, Alcohols, Enols, and Thiols.
t-Butoxycarbonylation of Amides, Lactams, and Carbamates.
In the presence of 4-Dimethylaminopyridine, Boc2O is a strong acylating agent able to react with the weakly nucleophilic amide and carbamate groups under anhydrous conditions. The reaction probably involves a 1-t-butoxycarbonyl-4-dimethylaminopyridinium ion intermediate (eq 3).24 This enhanced reactivity has led to numerous interesting synthetic applications. A wide range of amides, lactams, and urethanes have been converted to the corresponding Boc derivatives using Boc2O as reagent and DMAP as catalyst.
N-t-Butoxycarbonylation of Pyrroles and Indoles.
Activation of the Carboxyl Group. Formation of Esters and Anhydrides.
1-(t-Butoxycarbonyl)imidazole; 1-N-(t-Butoxycarbonyl)-1H-benzotriazole 3-N-Oxide; 2-(t-Butoxycarbonyloxyimino)-2-phenylacetonitrile; N-(t-Butoxycarbonyloxy)phthalimide; N-(t-Butoxycarbonyloxy)succinimide; 1-t-Butoxycarbonyl-1,2,4-triazole; t-Butyl Azidoformate; t-Butyl Chloroformate.
1. Greene, T. W.; Wuts, G. M. Protective Groups in Organic Synthesis 2nd ed.; Wiley: New York, 1991; p 327.
2. Bodansky, M. Principles of Peptide Chemistry; Springer; New York, 1984; p 99.
3. Flynn, D. L.; Zelle, R. E.; Grieco, P. A. JOC 1983, 48, 2424.
4. Gunnarsson, K.; Grehn, L.; Ragnarsson, U. AG(E) 1988, 27, 400.
5. Grehn, L.; Ragnarsson, U. AG(E) 1984, 23, 296.
6. Pope, B. M.; Yamamoto, Y.; Tarbell, D. S. OS 1977, 57, 45.
7. Benoiton, N. L.; Lee, Y. C.; Steinaur, R.; Chen, F. M. F. Int. J. Pept. Protein Res. 1992, 40, 559.
8. Pozdnev, V. F. Khim. Prir. Soedin. 1971, 384 (CA 1971, 75, 110 568x).
9. Pope, B. M.; Yamamoto, Y.; Tarbell, D. S. PNA 1972, 69, 730.
10. Moroder, L.; Hallett, A.; Wünsch, E.; Keller, O.; Wersin, G. Z. Physiol. Chem. 1976, 357, 1652.
11. Keller, O.; Keller, W. E.; van Look, G.; Wersin, G. OS 1985, 63, 160.
12. Harris, R. B.; Wilson, I. B. TL 1983, 24, 231.
13. Einhorn, J.; Einhorn, C.; Luche, J. L. SL 1991, 37.
14. Guzman, A.; Quintero, C.; Muchowski, J. M. CJC 1991, 69, 2059.
15. Beak, P.; Lee, W. K. JOC 1993, 58, 1109.
16. Muchowski, J. M.; Venuti, M. C. JOC 1980, 45, 4798.
17. Dalla Croce, P.; La Rosa, C.; Ritieni, A. JCR(S) 1988, 346.
18. Fishwick, C. W. G.; Storr, R. C.; Manley, P. W. CC 1984, 1304.
19. Fiakpui, C. Y.; Knaus, E. E. CJC 1987, 65, 1158.
20. Hofmann, K.; Finn, F.; Kiso, Y. JACS 1978, 100, 3585.
21. Stanetty, P.; Koller, H.; Mihovilovic, M. JOC 1992, 57, 6833.
22. Clark, R. D.; Muchowski, J. M.; Fisher, L. E.; Flippin, L. A.; Rebke, D. B.; Souchet, M. S 1991, 871.
23. Kerrick, S. T.; Beak, P. JACS 1991, 113, 9708.
24. Guibé-Jampel E.; Wakselman, M. S 1977, 772.
25. Shai, Y.; Kirk, K. L.; Channing, M. A.; Dunn, B. B.; Lesniak, M. A.; Eastman, R. C.; Finn, R. D.; Roth, J.; Jakobsen, K. A. B 1989, 28, 4801.
26. Krapcho, A. P.; Kuell, C. S. SC 1990, 20, 2559.
27. Scott, J. W.; Parker, D.; Parrish, D. R. SC 1981, 11, 303.
28. Masukiewicz, E.; Rzeszotarska, B.; Szczerbaniewicz, J. OPP 1992, 24, 191.
29. Egbertson, M. S.; Homnick, C. F.; Hartman, G. D. SC 1993, 23, 703.
30. Prugh, J. D.; Birchenough, L. A.; Egberston, M. S. SC 1992, 22, 2357.
31. Perseo, G.; Piani, S.; De Castiglione, R. Int. J. Pept. Protein Res. 1983, 21, 227.
32. Ponnusamy, E.; Fotatar, U.; Spisni, A.; Fiat, D. TL 1986, 48.
33. Kemp, D. S.; Carey, R. I. JOC 1989, 54, 3640.
34. Chen, F. M. F.; Benoiton, N. L. CJC 1987, 65, 1224.
35. Pozdnev, V. F. Khim. Prir. Soedin. 1982, 129 (CA 1983, 97, 92 706p).
36. Pozdnev, V. F. Bioorg. Khim. 1977, 3, 1604 (CA 1978, 88, 62 595y).
37. Pozdnev, V. F. ZOB 1977, 48, 476 (CA 1978, 89, 24 739m).
38. Pozdnev, V. F. Bioorg. Khim. 1986, 12, 1013.
39. Harris, R. B.; Wilson, I. B. JBC 1983, 258, 1357.
40. Losse, G.; Naumann, W.; Raddatz, H. ZC 1983, 23, 22.
41. Altman, Shoef, N.; Wilchek, M.; Warshawsky, A. CC 1985, 1133.
42. Lee, B. H.; Miller, M. J. JOC 1983, 38, 24.
43. Baldwin, J. E.; Adlington, R. M.; Birch, J. B. TL 1985, 26, 5931.
44. Harris, R. B.; Wilson, I. B. Int. J. Pept. Protein Res. 1984, 23, 55.
45. Itoh, H.; Hagiwara, D.; Kamiya, T. BCJ 1977, 50, 718.
46. Pozdnev, V. F. ZOR 1977, 13, 2531 (CA 1978, 88, 89 063k).
47. Lecoq, A.; Marraud, M.; Aubry, A. TL 1991, 32, 2765.
48. Saito, S.; Nakajima, H.; Inaba, M.; Moriwake, T. TL 1989, 30, 837.
49. Cheung, S. T.; Benoiton, N. L. CJC 1977, 55, 906.
50. Hansen, D. W.; Pilipauskas, D. JOC 1985, 50, 945.
51. Rich, D. H.; Dhaon, M. K.; Dunlap, B.; Miller, S. P. F. JMC 1986, 29, 978.
52. Pietzonka, T.; Seebach, D. AG(E) 1992, 31, 1481.
53. Sakatani, M.; Hori, K.; Ohfune, Y. TL 1988, 29, 2983.
54. Bajwa, J. S. TL 1992, 33, 2955.
55. Li, W.-R.; Jiang, J.; Joullié, M. M. TL 1993, 34, 1413.
56. Houlihan, F.; Bouchard, F.; Fréchet, J. M. F.; Wilson, C. G. CJC 1985, 63, 153.
57. Aruze, I.; Okai, H.; Kouge, K.; Yamamoto, Y.; Koizumi, T. Chem. Express 1988, 3, 45.
58. Pozdnev, V. F. Int. J. Pept. Protein Res. 1992, 40, 407.
59. Klutchko, S.; O'Brien, P.; Hodges, J. C. SC 1989, 19, 2573.
60. Grehn, L.; Gunnarsson, K.; Ragnarsson, U. ACS 1986, B40, 745.
61. Baldwin, J. E.; Adlington, R. M.; Godfrey, C. R. A.; Gollins, D. W.; Smith, M; L. Russel, A. SL 1993, 51.
62. Davidsen, S. K.; May, P. D.; Summers, J. B. JOC 1991, 56, 5482.
63. Grehn, L.; Ragnarsson, U. S 1987, 275.
64. Grehn, L.; Gunnarsson, K.; Ragnarsson, U. ACS 1987, B41, 18.
65. Hiemstra, H.; Klaver, W. J.; Speckamp, W. N. TL 1986, 27, 1411.
66. Ohta, T.; Hosoi, A.; Kimura, T.; Nozoe, S. CL 1987, 2091.
67. Giovannini, A.; Savoia, D.; Umani-Ronchi, A. JOC 1989, 54, 228.
68. Klutchko, S.; Hamby, J. M.; Reilly, M.; Taylor, M. D.; Hodges, J. C. SC 1993, 23, 971.
69. Ohta, T.; Kimura, T.; Sato, N.; Nozoe, S. TL 1988, 29, 4303.
70. Ezquerra, J.; de Mendoza, J.; Pedregal, C.; Ramírez, C. TL 1992, 33, 5589.
71. Molina, M. T.; del Valle, C.; Escribano, A. M.; Ezquerra, J.; Pedregal C. T 1993, 49, 3801.
72. Ishizuka, T.; Kunieda, T. TL 1987, 28, 4185.
73. Grehn, L.; Gunnarsson, K.; Ragnarsson, U. CC 1985, 1317.
74. Ragnarsson, U.; Grehn, L. ACR 1991, 24, 285.
75. Connell, R. D.; Rein, T.; Åkermark, B.; Helquist, P. JOC 1988, 53, 3845.
76. Grehn, L.; Bondesson, U.; Pehk, T.; Ragnarsson, U. CC 1992, 1332.
77. Degerbeck, F.; Fransson, B.; Grehn, L.; Ragnarsson, U. JCS(P1) 1993, 11.
78. Gunnarsson, K.; Grehn, L.; Ragnarsson, U. AG(E) 1988, 27, 400.
79. Gunnarsson, K.; Ragnarsson, U. ACS 1990, 44, 944.
80. (a) Savrda, J.; Wakselman, M. CC 1992, 812. (b) Carpino, L. A.; Mansour, E.-S. M. E.; El-Faham, A. JOC 1993, 58, 4162.
81. Fuller, W. D.; Cohen, M. P.; Shabankaresh, M.; Blair, R. K.; Goodman, M.; Naider, F. R. JACS 1990, 112, 7414.
82. Grehn, L.; Ragnarsson, U. AG(E) 1985, 24, 400.
83. Cavelier-Frontin, F.; Achmad, S.; Verducci, J.; Pépe, G.; Jacquier, R. J. Mol. Struct. (Theochem) 1993, 105, 125.
84. Almeida, M. L. S.; Grehn, L.; Ragnarsson, U. CC 1987, 1250.
85. Almeida, M. L. S.; Grehn, L.; Ragnarsson, U. JCS(P1) 1988, 1905.
86. Araújo, M. J. S. M. P.; Ragnarsson, U.; Almeida, M. L. S.; Amaral Trigo, M. J. S. A. JCR(S) 1992, 110.
87. Iwanowicz, E. J.; Poss, M. A.; Lin, J. SC 1993, 23, 1443.
88. Bernatowicz, M. S.; Wu, Y.; Matsueda, G. R. TL 1993, 34, 3389.
89. Grehn, L.; Ragnarsson, U. AG(E) 1984, 23, 296.
90. Rawal, V. H.; Cava, M. P. TL 1985, 26, 6141.
91. Chen, W.; Cava, M. P. TL 1987, 28, 6025.
92. Woolridge, E. M.; Rokita, S. E. TL 1989, 30, 6117.
93. Leroy, J.; Cantacuzene, D.; Wakselman, C. S 1982, 313.
94. Franzén, H.; Grehn, L.; Ragnarsson, U. CC 1984, 1699.
95. Rachon, J.; Schöllkopf, U. LA 1981, 99.
96. Teulade, M. P.; Savignac, P.; About-Jaudet, E.; Colignon, N. SC 1989, 19, 71.
97. van Es, J. J. G. S.; Jaarveld, K.; van der Gen, A. JOC 1990, 55, 4063.
98. Esch, P. M.; Hiemstra, H.; Speckamp, W. N. T 1992, 48, 3445.

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