Organic Chemistry Portal
Reactions >> Protecting Groups >> Stability

tert-Butyl esters

T. W. Green, P. G. M. Wuts,
Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 372-381, 404-408, 728-731.



H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C
Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2
Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3
Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH
Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4
Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2


Aqueous phosphoric acid is an effective, environmentally benign, selective and mild reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers are tolerated. The reactions are high yielding, and the workup is convenient.
B. Li, M. Berliner, R. Buzon, C. K.-F. Chiu, S. T. Colgan, T. Kaneko, N. Keene, W. Kissel, T. Le, K. R. Leeman, B. Marquez, R. Morris, L. Newell, S. Wunderwald, M. Witt, J. Weaver, Z. Zhang, Z. Zhang, J. Org. Chem., 2006, 71, 9045-9050.

The combination of the tris-4-bromophenylamminium radical cation, commonly known as magic blue (MB•+), and triethylsilane mediates a mild OtBu deprotection. Magic blue catalytically facilitates the cleavage of the C-O bond in tert-butyl carbamates, carbonates, esters, and ethers in a high isolated yield under mild conditions, and sacrificial triethylsilane accelerates the reaction.
D. Hidasová, Tomáš Slanina, J. Org. Chem., 2023, 88, 6932-6938.

The hazardous Schmidt procedure for tert-butyl benzoate ester cleavage using NaH in DMF involves BAC2 ester cleavage by NaH-derived NaOH, rather than the proposed E2 elimination of isobutylene by DMF-derived NaNMe2. Powdered KOH in THF is a significantly safer and simpler alternative that effects cleavage of tert-butyl benozoates at ambient temperature in excellent yield.
E. Filali, G. C. Lloyd-Jones, D. A. Sale, Synlett, 2009, 205-208.

E. Filali, G. C. Lloyd-Jones, D. A. Sale, Synlett, 2009, 205-208.

An interesting example of a selective deprotection of tert-butyl esters is reported.
E. Marcantoni, M. Massaccesi, E. Torregiani, G. Bartoli, M. Bosco, L. Sambri, J. Org. Chem, 2001, 66, 4430-4432.

Conversion of tert-butyl esters to other functional groups

The reaction of tert-butyl esters with SOCl2 at room temperature provides acid chlorides in very good yields, whereas benzyl, methyl, ethyl, and isopropyl esters are essentially unreactive.
J. A. Greenberg, T. Sammakia, J. Org. Chem., 2017, 82, 3245-3251.