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Synthesis of α-keto carboxylic acids, esters and amides


Recent Literature

An efficient iodine-mediated oxidative esterification of acetophenones provides various α-ketoesters and esters in high yields in the presence of potassium xanthates. The potassium xanthate not only promotes oxidative esterification but also provides an alkoxy moiety for the reaction.
X. Luo, R. He, Q. Liu, Y. Gao, J. Li, X. Chen, Z. Zhu, Y. Huang, Y. Li, J. Org. Chem., 2020, 85, 5220-5230.

Copper-catalyzed aerobic oxidative esterification of acetophenones with alcohols using molecular oxygen gives a broad range of α-ketoesters in good yields. Mechanism studies evealed that the carbonyl oxygen in the ester mainly originated from dioxygen.
X. Xu, W. Ding, Y. Lin, Q. Song, Org. Lett., 2015, 17, 516-519.

In the presence of nucleophiles (alcohols or amines), ion-supported (di­acetoxyiodo)benzene promoted sp3 C-H oxidation of nitromethyl aryl ketones to provide the corresponding α-keto esters and amides in good yields. The reaction is ecofriendly and offers mild conditions, short reaction times, and a recyclable reagent.
X. Jang, B. Gan, J. Liu, Y. Xie, Synlett, 2016, 27, 2737-2741.

Visible light promotes a green and mild conversion of β-ketonitriles into α-ketoesters under catalyst-free conditions via singlet oxygen generation, oxidative C-H bond functionalization, and C-C σ-bond cleavage.
C. Xu, N.-N. Zhang, X.-j. Li, Y.-q. Ge, P.-h. Diao, C. Guo, Synlett, 2018, 29, 1065-1070.

A recyclable, bifunctional iron nanocomposite catalyzes an efficient synthesis of α-keto acids via oxidation of alkenes using TBHP as oxidant. A variety of alkenes with different functional groups were smoothly oxidized into their corresponding α-keto acids in good yields.
T. Song, Z. Ma, X. Wang, Y. Yang, Org. Lett., 2021, 23, 5917-5921.

A Cu-catalyzed oxidative amidation-diketonization reaction of terminal alkynes leads to α-ketoamides. In this copper-catalyzed radical process, O2 not only participates as the ideal oxidant but also undergoes dioxygen activation under ambient conditions.
C. Zhang, N. Jiao, J. Am. Chem. Soc., 2010, 132, 28-29.

Benzylimidates can directly be converted to primary α-ketoamides by using molecular oxygen as an oxidant in the presence of copper(II) salt. The reaction offers a wide substrate scope and operationally mild conditions.
Y. Kumar, M. Shaw, R. Thakur, A. Kumar, J. Org. Chem., 2016, 81, 6617-6625.

A simple and efficient oxidative coupling of diazoesters and α-diazoketones with NH4I provides primary oxamates and α-ketoamides in good yields. This metal-free protocol is performed under mild conditions and has a wide substrate scope.
H. Wang, Y. Zhao, Y. Zheng, S. Fang, J. Li, X. Wan, J. Org. Chem., 2020, 85, 3050-3058.

The use of pyridine-N-oxides as oxidants under molecular iodine catalysis enables a rapid, metal-free dioxygenation of ynamides. Furthermore, this protocol could be extended to nonactivated alkynes, such as diarylacetylenes, to provide various benzil derivatives.
S. W. Kim, T.-W. Um, S. Shin, J. Org. Chem., 2018, 83, 4703-4711.

2,3-Dichloropyridine N-oxide as oxygen transfer reagent enables gold(I)-catalyzed oxidation of alkynes to 1,2-dicarbonyls in the absence of any acid additives and under mild conditions. The developed strategy is also effective for ynamides, alkynyl ethers/thioethers, and substrates bearing highly acid-sensitive groups. A one-pot heterocyclization provides six-membered azaheterocycles.
A. Yu. Dubovtsev, N. V. Shcherbakov, D. V. Dar'in, V. Yu. Kukushkin, J. Org. Chem., 2020, 85, 745-757.

An amination reaction of in situ generated gem-difluoro-enolates with nitrosoarenes furnished α-ketoamides in very high yields. This nitroso aldol reaction is very fast (typically completed within 5 min) and scalable and tolerates various sensitive functional groups. Amination with azodicarboxylates smoothly produced fluorinated α-amino ketones.
M. K. Reddy, I. Ramakrishna, M. Baidya, Org. Lett., 2018, 20, 4579-4583.


The cross-coupling reaction of α-oxo acid chlorides with carbamoylsilanes provides vicinal tricarbonyl amides in good yields under mild conditions. The reaction of carbamoylsilanes with oxalyl chloride is accompanied by decarbonylation to give vicinal tricarbonyl amides.
Y. Han, Y. Li, S. Han, P. Zhang, J. Chen, Synthesis, 2019, 51, 2977-2983.