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Reactions >> Protecting Groups >> Stability

Benzyl esters

T. W. Green, P. G. M. Wuts,
Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 372-381, 415-419, 728-731.



H2O: pH < 1, 100C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100C
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 of carboxylic acids

Triethylamine mediates esterification reactions between 2-benzyloxy-1-methylpyridinium triflate and carboxylic acids. Alcohols, phenols, amides, and other sensitive functionality are not affected; a dual role for triethylamine as a promoter and a scavenger is postulated.
J. Tummatorn, P. A. Albiniak, G. B. Dudley, J. Org. Chem., 2007, 72, 8962-8964.

A direct benzylation of carboxylic acids with toluene via palladium-catalyzed C-H acyloxylation under 1 atm of oxygen demonstrates good functional group tolerance and high yields. The method provides a facile, atom-economic, and efficient synthesis of benzyl esters.
H. Liu, G. Shi, S. Pan, Y. Jiang, Y. Zhang, Org. Lett., 2013, 15, 4098-4101.

An esterification of primary benzylic C-H bonds with carboxylic acids using di-tert-butyl peroxide as an oxidant is catalyzed by novel ionic iron(III) complexes containing an imidazolinium cation. The reaction offers a broad generality and tolerates sterically hindered starting materials.
B. Lu, F. Zhu, H.-M. Sun, Q. Shen, Org. Lett., 2017, 19, 1132-1135.

Other Syntheses of Benzyl esters

A catalytic transesterification is promoted by a tetranuclear zinc cluster. The mild reaction conditions enabled the reactions of various functionalized substrates to proceed in very good yield. A large-scale reaction under solvent-free conditions offers high environmental and economical advantages.
T. Iwasaki, Y. Maegawa, Y. Hayashi, T. Ohshima, K. Mashima, J. Org. Chem., 2008, 73, 5147-5150.

Copper(II) catalyzes a cross dehydrogenative coupling (CDC) reaction of aldehydes with alkylbenzenes in the presence of TBHP to yield benzylic esters.
S. K. Rout, S. Guin, K. K. Ghara, A. Banerjee, B. K. Patel, Org. Lett., 2012, 14, 3982-3985.


In situ generation of molecular hydrogen by addition of triethylsilane to palladium on charcoal results in rapid and efficient reduction of multiple bonds, azides, imines, and nitro groups, as well as deprotection of benzyl and allyl groups under mild, neutral conditions.
P. K. Mandal, J. S. McMurray, J. Org. Chem., 2007, 72, 6599-6601.

In situ preparation of an active Pd/C catalyst from Pd(OAc)2 and charcoal in methanol enables a simple, highly reproducible protocol for the hydrogenation of alkenes and alkynes and for the hydrogenolysis of O-benzyl ethers. Mild reaction conditions and low catalyst loadings, as well as the absence of contamination of the product by palladium residues, make this a sustainable, useful process.
F.-X. Felpin, E. Fouquet, Chem. Eur. J., 2010, 12440-12445.

Ammonia, pyridine and ammonium acetate were extremely effective as inhibitors of Pd/C catalyzed benzyl ether hydrogenolysis. While olefin, Cbz, benzyl ester and azide functionalities were hydrogenated smoothly, benzyl ethers were not cleaved.
H. Sajiki, Tetrahedron Lett., 1995, 36, 3465-3468.

Benzyl esters of various acids can be chemoselectively cleaved on treatment with nickel boride in methanol at ambient temperature to give the parent carboxylic acids in high yields. Esters such as methyl, ethyl, tert-butyl, and trityl esters as well as benzyl ethers, tert-butyl ethers, and N-benzylamides remain unaffected under these conditions.
J. M. Khurana, R. Arora, Synthesis, 2009, 1127-1130.