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Overview of commonly used protective groups–di-tert-butyl carbonic anhydride (Boc)2O
[English name]Di-t-Butyl Dicarbonate
[Molecular formula] C10H18O5
[Molecular weight] 218.25
【CA registration number】24424-99-5
[Abbreviation and alias](Boc)2O
[Physical properties] Low melting point colorless crystal or colorless liquid, mp 22~24 lepidolite℃, bp 56~57°C/0.5 mmHg (66.66 Pa), d 0.950 g/cm3. Soluble in most organic solvents, such as carbon tetrachloride, tetrahydrofuran, dioxane, alcohol, acetone, acetonitrile, N,N-dimethylformamide, etc., and insoluble in cold water.
【Preparation and Products】Sold by domestic and foreign reagent companies. It can also be prepared by directly reacting phosgene with tert-butyl carbonate under the catalysis of 1,4-diazabicyclo[2.2.2]octane.
【Precautions】It is sensitive to moisture and flammable. It needs to be stored in the refrigerator and used at temperatures below 80 °C.
Application of commonly used protective groups–di-tert-butyl carbonic anhydride (Boc)2O
In organic chemical reactions, (Boc)2O is often used as a tert-butoxy carbonylation reagent for substrates such as amines, phenols, thiols, amides, lactams, and carbamates. The reaction rate is very fast and the yield is relatively high.
tert-butoxycarbonylation reaction (protection of functional groups) Due to the poor stability of acid halide reagents, (Boc)2O is widely used as the protecting group of amino groups [1,2]. This protective group can be removed by the action of trifluoroacetic acid. Aliphatic amines, alicyclic amines, aromatic amines and heterocyclic amines can all react with (Boc)2O. Under appropriate conditions, multifunctional compounds such as diamines (formula 1), aminoalcohols, amino acids, etc. can also react selectively with (Boc)2O [3].
For other nitrogen-containing compounds (such as amides, lactams, carbamates, etc.), (Boc)2O can also be used as a better protective reagent. Under anhydrous conditions, it can react with amides and carbamates which are weakly nucleophilic. In solutions of triethylamine and N,N-dimethylaminopyridine (DMAP) in CH2Cl2, secondary amide and lactam compounds can also be protected by Boc (formula 2) [4,5].
Both carbanions and Schiff bases can react with (BOC)2O under appropriate conditions to generate the corresponding tert-butoxycarbonyl compound (Formula 3) [6].
Exchange of amino protecting groups Benzyloxycarbonyl (Cbz) and Fmoc are also often used as protecting groups for amino groups. In the presence of a slight excess of (Boc)2O, the amino compound protected by Cbz or Fmoc can undergo protective group exchange and be converted into a Boc-protected amino compound (Formula 4) [7].
Activation of carboxyl group (Boc)2O can not only be used as a protecting group, but also can be used as an activating group of carboxyl group (Formula 5). This is mainly because the Boc- group is a better leaving group. It can leave under appropriate conditions after reacting with the carboxyl group, leaving the carboxyl part in a non-electronic neutral state with better electrophilicity [8].
Under appropriate conditions, phenols, alcohols, enols and thiols can also react with (Boc)2O on functional groups such as hydroxyl groups to form O-Boc protecting groups.
References
1. Liu, G.; Sieburth, S. M. Org. Lett, 2003,5,4677.
2. Ouchi, T.; Uchida, T.; Arimura, H.; Ohya, Y. Biomacromolecules 2003, 4, 477.
3. Busnel, 0.; Carreaux, F.; Carboni, B.; Pethe, S.; Goff, S. V.-L.; Mansuy, D.; Boucher, J.-L. Bioorg.Med Chem. 2005 ,13, 2373.
4. Gyonfalvi, S.; Szakonyi, Z.; Fulop, F. Tetrahedron: Asymmetry 2003,14,3965.
5. Janetka, J. W.; Furness, M. S.; Zhang, X.; Coop, A.; Folk, J. E.; Mattson, M. V,; Jacobson, A. E.; Rice, K. C.J. Org. Chem. 2003, 68, 3976 .
6. Robifluoroborate, A.; Julienne, K.; Meslin, J. C.; Deniaud, D. Tetrahedron Lett. 2004, 45, 9557.
7. Lloyd, R. C.; Smith, M. E. B.; Brick, D.; Taylor, S. J. C.; Chaplin, D. A.; McCague, R. Org. Proc. Res.Dev. 2002, 6, 762.
8. Ma, D. W.; Xia, C. F. Org. Lett. 2001,3,2583.
