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.
Stability
| 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 |
Protection
Treatment of various free amino acids with 1.1 equivalents of
bis(trifluoromethanesulfonyl)imide in tert-butyl acetate directly
afforded tert-butyl esters with free amino groups quickly and in good
yields. In addition, various carboxylic acids and alcohols without amino groups
were converted into tert-butyl esters and ethers, respectively, in high
yields in the presence of catalytic amounts of Tf2NH.
C. Ogasa, K. Kayano, K. Namba, Synlett, 2024,
35,
235-239.
Treatment of various free amino acids with 1.1 equivalents of
bis(trifluoromethanesulfonyl)imide in tert-butyl acetate directly
afforded tert-butyl esters with free amino groups quickly and in good
yields. In addition, various carboxylic acids and alcohols without amino groups
were converted into tert-butyl esters and ethers, respectively, in high
yields in the presence of catalytic amounts of Tf2NH.
C. Ogasa, K. Kayano, K. Namba, Synlett, 2024,
35,
235-239.
Deprotection
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
Reactions of tert-butyl esters with α,α-dichlorodiphenylmethane as the
chlorinating agent and SnCl2 as catalyst generate acid chloride
intermediates in situ, that were subsequently used in reactions with a variety
of alcohols and amines to afford the corresponding esters and amides in high
yields under mild reaction conditions.
V. H. Tran, A. T. Nguyen, H.-K. Kim, J. Org. Chem., 2023, 88,
13291-13302.
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.
