Synthesis of α-keto carboxylic acids, esters and amides
A chemoselective oxidation of α-hydroxy acids to α-keto acids is catalyzed by 2-azaadamantane N-oxyl (AZADO), a nitroxyl radical catalyst. The use of molecular oxygen as a cooxidant enables the desired chemoselective oxidation to α-keto acids, that are labile and can easily release CO2 under oxidation conditions.
K. Furukawa, H. Inada, M. Shibuya, Y. Yamamoto, Org. Lett., 2016, 18, 4230-4233.
Natural sunlight and air enable an efficient oxidation of α-aryl halogen derivatives to the corresponding α-aryl carbonyl compounds at room temperature through the combination of photocatalysis and organocatalysis. A plausible mechanism was proposed on the basis of the mechanistic studies.
Y. Su, L. Zhang, N. Jiao, Org. Lett., 2011, 13, 2168-2171.
The reaction of aryl diazoacetates with H2O and diethyl azodicarboxylate (DEAD) catalyzed by dirhodium acetate gives aryl α-keto esters in high yields.
Z. Guo, H. Huang, Q. Fu, W. Hu, Synlett, 2006, 2486-2488.
An efficient intermolecular interception of alkyl azides by diazo(aryl)acetates in the presence of dirhodium tetraoctanoate gives unstable α-imino esters without overaddition of carbenoids to the C-N double bonds. After acidic workup, the corresponding α-keto esters were obtained in very good yields.
P. Gu, X.-P. Wu, Y. Su, X.-Q. Li, P. Xue, R. Li, Synlett, 2014, 25, 535-538.
A copper-catalyzed one-pot strategy for the synthesis of α-ketoamides from 1-arylethanols is highly efficient and delivers product in very good yields via alcohol oxidation, sp3 C-H oxidation, and oxidative amidation.
N. Sharma, S. S. Kotha, N. Lahiri, G. Sekar, Synthesis, 2015, 47, 726-736.
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.
A conjugate addition of ethyl cyanoacetates to chalcones and subsequent iodine-promoted aerobic oxidation provides various α,δ-dicarbonyl esters. The present protocol features mild reaction conditions, high efficiency, easily available starting materials, and broad substrate scope.
H. Xu, M.-Y. Weng, H. Chen, Z. Zhang, Synthesis, 2020, 52, 1841-1846.
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.