BOC Protection and Deprotection

The BOC (tert-butoxycarbonyl) group is used to protect amines in synthetic reactions.

Di-tert-butyl dicarbonate, BOC₂O (also known as di-tert-butyl pyrocarbonate or BOC anhydride), triethylamine (TEA), and tetrahydrofuran (THF) are commonly used to add the BOC group. The amine attacks a carbonyl site of BOC₂O, creating a t-butyl carbonate leaving group that breaks down to carbon dioxide gas and t-butoxide. The base then abstracts a proton from the positively charged amine.

Trifluoroacetic acid (TFA) and dichloromethane (DCM) are commonly used to remove the BOC group. The protected amine is first protonated by TFA, triggering the production of a t-butyl cation and carbamic acid, which is decarboxylated to yield the amine.

Since both protection and deprotection reactions produce CO₂ gas, closed systems should not be used.

Lab Tips

The BOC group can also be added without the use of a solvent. ^[1]
One way to selectively protect primary amines in polyamines is to use t-BuOCO₂Ph in CH₂Cl₂, or DMF. ^[2]
ZnBr₂ in CH₂Cl₂ selectively cleaves secondary N-BOC groups, leaving primary N-BOC groups untouched. ^[3]
Montmorillonite K10 clay in ClCH₂CH₂Cl selectively cleaves aromatic N-BOC groups, leaving aliphatic N-BOC amines intact. ^[4]

_{1. Jia, X., Huang, Q, Li, J., Li, S., Yang, Q. Environmentally benign N-Boc protection under solvent-and catalyst-free conditions. Synlett 2007, 5, 0806-0808.
2. Pittelkow, M., Lewinsky, R., Christensen, J.B. Selective synthesis of carbamate protected polyamines using alkyl phenyl carbonates. Synthesis 2002, 15, 2195-2202.
3. Nigama, S. C., Mann, A., Taddei, M., Wermutha, C-G. Selective removal of the tert-butoxycarbonyl group from secondary amines: ZnBr₂ as the deprotecting reagent. Synth. Commun. 1989, 19(18), 3139-3142.
4. Shaikh, N. S., Gajare, A. S., Deshpande, V. H., Bedekar, A. V. A mild procedure for the clay catalyzed selective removal of the tert-butoxycarbonyl protecting group from aromatic amines. Tetrahedron Lett. 2000, 41(3), 385-387.}