Pivalic acid esters
Pv-OR, Pivalate ester, Pivalates
T. W. Green, P. G. M. Wuts,
Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 170-173, 712-715.
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
A simple and efficient protocol for pivaloylation of alcohols without using a
catalyst under solvent-free conditions offers short reaction time, high yields,
simple workup, and no need for further purification. Selectivity was observed
between primary alcohols vs. secondary alcohols and aliphatic alcohols vs.
phenols.
C. B. Rao, B. Chinnababu, Y. Venkateswarlu, J. Org. Chem., 2009,
74, 8856-8858.
4-(N,N-Dimethylamino)pyridine hydrochloride (DMAP·HCl) was used as a
recyclable catalyst for the acylation of inert alcohols and phenols under
base-free conditions. The catalyst can be reused more than eight times without
loss in activity and works with various acylating reagents.
Z. Liu, Y. Liu, Q. Wang, Org. Lett., 2014,
16, 236-239.
Inexpensive phosphoric acid
(H3PO4) catalyzes a safe and simple acylation of alcohols with acid anhydrides.
In situ-generated diacylated mixed anhydrides are proposed as the active
species - acting as efficient
catalytic acyl transfer reagents. A
23 g scale synthesis of an ester was demonstrated.
H. Hayashi, S. Yasukochi, T. Sakamoto, M. Hatano, K. Ishihara, J. Org. Chem., 2021, 86,
5197-5212.
Bi(OTf)3 catalyzes mild acylations of alcohols with acid
anhydrides. Sterically demanding or tertiary alcohols could be acylated smoothly.
Less reactive acylation reagents such as benzoic and pivalic anhydride are also
activated. Methanolysis of the unreacted anhydrides into easily separable methyl
ester realized quite easy separations of the desired pivaloylated or benzoylated
products.
A. Orita, C. Tanahashi, A. Kakuda, J. Otera, J. Org. Chem., 2001,
66, 8926-8934.
Vanadyl triflate efficiently catalyzes a nucleophilic acyl substitution of
anhydrides with a myriad array of alcohols, amines, and thiols in high yields
and high chemoselectivity. By using mixed-anhydride technique, oleate and
peptide syntheses can be achieved.
C.-T. Chen, J.-H. Kuo, C.-H. Li, N. B. Barhate, S.-W. Hon, T.-W. Li, S.-D. Chao,
C.-C. Liu, Y.-C. Li, I.-H. Chang, J.-S. Lin, C.-J. Liu, Y.-C. Chou, Org. Lett., 2001, 3,
3729-3732.
Deprotection
Acyloxymethyl radicals, that add to imines, were generated from the
corresponding iodomethyl esters by the action of dimethylzinc or triethylborane.
A facile hydrolysis of the acyloxy moiety of the adducts gave the corresponding
amino alcohols in good yield.
K.-i. Yamada, M. Nakano, M. Maekawa, T. Akindele, K. Tomioka, Org. Lett.,
2008,
10, 3805-3808.
The reaction of different esters, thioesters and amides derived from pivalic,
benzoic and 4-tert-butylbenzoic acids with an excess of lithium and a
catalytic amount of naphthalene led, after methanolysis, to the corresponding
alcohols, thiols and amines, respectively, through a reductive non-hydrolytic
procedure.
C. Behloul, D. Guijarro, M. Yus,
Synthesis, 2006, 309-314.
Acetyl-, benzoyl- and pivoyl-protected alcohols and phenols undergo smooth
deacylation in a two-phase system of powdered NaOH and Bu4NHSO4
in THF or CH2Cl2.
R. D. Crouch, J. S. Burger, K. A. Zietek, A. B. Cadwallader, J. E. Bedison, M.
M. Smielewska, Synlett,
2003, 991-992.
