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Reactions >> Protecting Groups >> Stability

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.



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


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.


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.