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Reactions >> Protecting Groups >> Stability

Methyl esters

T. W. Green, P. G. M. Wuts,
Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 372-381, 383-387, 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


A convenient and efficient sonochemical method for methyl esterification of carboxylic acids is catalyzed by polymer-supported triphenylphosphine in the presence of 2,4,6-trichloro-1,3,5-triazine and Na2CO3. Methyl esters of various carboxylic acids bearing reactive hydroxyl groups as well as acid- or base-labile functionalities could be rapidly prepared within short times in good to excellent yields in high purities without column chromatography.
S. Jaita, W. Phakhodee, M. Pattarawarapan, Synlett, 2015, 26, 2006-2008.


Sc(OTf)3 catalyses a direct transesterification of carboxylic esters in boiling alcohols. Methyl, ethyl, isopropyl, and allyl esters were prepared from various substrates in high yields. The application of microwave irradiation led to significantly reduced reaction times.
N. Remme, K. Koschek, C. Schneider, Synlett, 2007, 491-493.


A copper-catalyzed O-methylation of carboxylic acids using dimethyl sulfoxide (DMSO) as the methyl source exhibits a broad substrate scope and excellent functional group tolerance. Mechanistic studies indicate that a methyl radical is generated from dimethyl sulfoxide.
J. Jia, Q. Jiang, A. Zhao, B. Xu, Q. Liu, W.-P. Luo, C.-C. Guo, Synthesis, 2016, 48, 421-428.


A highly effective synthesis of methyl esters from benzylic alcohols, aldehydes, or acids via copper-catalyzed C-C cleavage from tert-butyl hydroperoxide is easily accessible and practical and offers an alternative to the traditional way.
Y. Zhu, H. Yan, L. Lu, D. Liu, G. Rong, J. Mao, J. Org. Chem., 2013, 78, 9898-9905.


Dimethylcarbonate is a nontoxic and green methylating reagent. A base-catalyzed methyl transfer from dimethylcarbonate to carboxylic acids offers high selectivity for esterification and mild reaction conditions, that enable conservation of stereochemistry at epimerizable stereocenters. Isotope-labeling studies suggest a mechanism via direct methyl transfer from dimethylcarbonate to the substrate.
Y. Ji, J. Sweeney, J. Zoglio, D. J. Gorin, J. Org. Chem., 2013, 78, 11606-11611.


A Cu-catalyzed nondecarboxylative methylation of carboxylic acids with methylboronic acid proceeds in air as sole oxidant and offers a strategy for replacing toxic, electrophilic alkylating reagents. An isotope-labeling study supports an oxidative cross-coupling mechanism, in analogy to that proposed for Chan-Lam arylation.
C. E. Jacobson, N. Martinez-Muņoz, D. J. Gorin, J. Org. Chem., 2015, 80, 7305-7310.


Other Syntheses of Methyl Esters


A readily accessible catalyst system consisting of Pd/charcoal in combination with bismuth(III) nitrate and tellurium metal enables an efficient aerobic oxidative methyl esterification of primary alcohols, exhibits a broad substrate scope, and is effective with both activated and unactivated alcohols bearing diverse functional groups. The Bi and Te additives significantly increase the reaction rate, selectivity, and overall product yields.
A. B. Powell, S. S. Stahl, Org. Lett., 2013, 15, 5072-5075.


Deprotection


N,N-diarylammonium pyrosulfate efficiently catalyzes the hydrolysis of esters under organic solvent-free conditions. This reverse micelle-type method is successfully applied to the hydrolysis of various esters without the decomposition of base-sensitive moieties and without any loss of optical purity for α-heterosubstituted carboxylic acids.
Y. Koshikari, A. Sakakura, K. Ishihara, Org. Lett., 2012, 14, 3194-3197.