Di-tert-butyl dicarbonate

Di-tert-butyl dicarbonate is a reagent widely used in organic synthesis.^[1] This carbonate ester reacts with amines to give N-tert-butoxycarbonyl or so-called t-BOC derivatives. These derivatives do not behave as amines, which allows certain subsequent transformations to occur that would have otherwise affected the amine functional group. The t-BOC can later be removed from the amine using acids. Thus, t-BOC serves as a protective group, for instance in solid phase peptide synthesis. It is stable to most bases and nucleophiles, allowing for an orthogonal Fmoc protection.

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Protection and deprotection of amines

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 t-BOC in amino acids can be accomplished with strong acids such as trifluoroacetic acid neat or in dichloromethane, or with HCl in methanol.^{[2] [3]}

Other uses

The synthesis of 6-acetyl-1,2,3,4-tetrahydropyridine, an important bread aroma compound from 2-piperidone was accomplished using t-boc anhydride.^[4] (See Maillard reaction). The first step in this reaction sequence is the formation of the carbamate from the reaction of the secondary amine with boc anhydride in acetonitrile with DMAP as a base.

Preparation

Di-tert-butyl dicarbonate is inexpensive, so it is usually purchased. Classically, this compound is prepared from tert-butanol, carbon dioxide, phosgene, using DABCO as a base:^[5]

References

1. ^ Wakselman, M. “Di-t-butyl Dicarbonate” in Encyclopedia of Reagents for Organic Synthesis (Ed: L. Paquette) 2004, J. Wiley & Sons, New York. doi:10.1002/047084289.
2. ^ Robert M. Williams, Peter J. Sinclair, Duane E. DeMong, Daimo Chen, and Dongguan Zhai, 4-Morpholinecarboxylic acid, 6-oxo-2,3-diphenyl-, 1,1-dimethylethyl ester, (2S,3R)-, Organic Syntheses, Vol. 80, p.18 (2003)
3. ^ E. A. Englund, H. N. Gopi, D. H. Appella, Org. Lett., 2004, 6, 213-215. doi:10.1021/ol0361599
   D. M. Shendage, R. Fröhlich, G. Haufe, Org. Lett., 2004, 6, 3675-3678. doi:10.1021/ol048771l
4. ^ Tyler J. Harrison and Gregory R. Dake, An Expeditious, High-Yielding Construction of the Food Aroma Compounds 6-Acetyl-1,2,3,4-tetrahydropyridine and 2-Acetyl-1-pyrroline, J. Org. Chem., 2005; 70(26) pp 10872 - 10874. doi:10.1021/jo051940a
5. ^ Barry M. Pope, Yutaka Yamamoto, and D. Stanley Tarbell, Dicarbonic acid, bis(1,1-dimethylethyl) ester, Organic Syntheses, Coll. Vol. 6, p.418 (1988); Vol. 57, p.45 (1977).