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.
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.
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.
Flexible and chemoselective methods for the transition-metal-free oxidation of amides provide α-keto amides and α-hydroxy amides. These highly valuable motifs are accessed in good to excellent yields and stereoselectivities with high functional group tolerance.
A. de la Torre, D. Kaiser, N. Maulide, J. Am. Chem. Soc., 2017, 139, 6578-6581.
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.
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.
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 transition-metal-free oxidative C-C bond cleavage process for a broad range of ester and dicarbonyl compounds involves carbanion addition to nitrosobenzene and proceeds via fragmentation of a previously unobserved oxazetidin-4-one heterocycle.
J. N. Payette, H. Yamamoto, J. Am. Chem. Soc., 2008, 130, 12276-12278.
A direct metal-free α-hydroxylation of α-unsubstituted β-oxoesters and β-oxoamides using m-chloroperbenzoic acid as the oxidant enables straightforward metal-free access to important α-hydroxy-β-dicarbonyl moieties under mild reaction conditions. Furthermore, the hydroxylated products can readily be converted into vicinal tricarbonyl compounds, which are useful synthetic precursors.
H. Asahara, N. Nishiwaki, J. Org. Chem., 2014, 79, 11735-11739.
An efficient gold(I)-catalyzed oxidation of COR2-functionalized internal alkynes provides α,β-diketoesters, 1,2,3-triketones, and α,β-diketoamides in good yields under mild conditions in the presence of 2,6-dichloropyridine N-oxide. The utility of these compounds was demonstrated by facile one-pot syntheses of azaheterocycles.
A. Y. Dubovtsev, D. V. Dar'in, V. Y. Kukushkin, Org. Lett., 2019, 21, 4116-4119.
The use of phenyliodine(III) bis(trifluoroacetate) enables a facile and direct oxidation of readily available β-ketoamides to provide vicinal tricarbonyl amides in good yields. This approach is a valuable addition to the group of traditional methods already available.
Y. Liu, Z. Zhang, Y. Wan, G. Zhang, Z. Li, J. Bi, N. Ma, T. Liu, Q. Liu, J. Org. Chem., 2017, 82, 3901-3907.
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.
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.
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.