Categories: C=O Bond Formation > Synthesis of ketones >
Synthesis of ketones by oxidation of benzylic substrates
Cost-effective and widely applicable protocols for controlled and predictably selective oxidation of methyl-/alkylarenes to corresponding value-added carbonyls have been developed, using a surfactant-based oxodiperoxo molybdenum catalyst in water and hydrogen peroxide (H2O2) as an environmentally benign green oxidant without any external base, additive, or cocatalyst.
P. Thiruvengetam, D. K. Chand, J. Org. Chem., 2022, 87, 4061-4077.
The presence of KBr enabled a direct benzylic oxidation of alkylarenes via C-H bond abstraction using oxone as oxidant under mild conditions. This reaction proceeded with excellent selectivity by thermal oxidation or photooxidation to provide a broad range of aryl ketones in high yields.
K. Moriyama, M. Takemura, H. Togo, Org. Lett., 2012, 14, 2414-2417.
The use of NaClO/TEMPO/Co(OAc)2 enabled a benzylic oxidation of alkyl arenes to yield various aromatic aldehydes and ketones in very good yields. The reaction reactivity, selectivity, and scope of the reaction were investigated.
C. Jin, L. Zhang, W. Su, Synlett, 2011, 1435-1438.
Ru complexes with tridentate hybrid ligands showed a very strong catalytic activity in water at room temperature for benzylic C-H oxidation. Whereas NHCs with a stronger donor ability stabilize the Ru center; nitrogen ligands with a relatively weaker donor ability release from the Ru center, so that they induce a reaction.
C.-B. Bo, Q. Bu, X. Li, G. Ma, D. Wei, C. Guo, B. Dai, N. Liu, J. Org. Chem., 2020, 85, 4324-4334.
The cationic complex [(pymox-Me2)RuCl2]+BF4- is a highly effective catalyst for the C-H bond oxidation of aryl alkanes in water using tert-butyl hydroperoxide as oxidant to yield various aryl ketones at room temperature in water as solvent. A solvent-caged oxygen rebounding mechanism via a Ru(IV)-oxo intermediate species is suggested.
C. S. Yi, K.-H. Kwon, D. W. Lee, Org. Lett., 2009, 11, 1567-1569.
o-Iodoxybenzoic acid (IBX) was found to be highly effective in oxidations adjacent to carbonyl and benzylic functionalities to form either α,β-unsaturated carbonyl compounds or conjugated aromatic carbonyl systems. Fine-tuning of the reaction conditions allowed remarkably selective transformations within multifunctional substrates.
K. C. Nicolaou, T. Montagnon, P. S. Baran, Y.-L. Zhong, J. Am. Chem. Soc., 2002, 124, 2245-2258.
Permanganate supported on active manganese dioxide can be used effectively for the oxidation of arenes, alcohols and sulfides under heterogeneous or solvent-free conditions.
A. Shaabania, P. Mirzaeia, S. Naderia, D. G. Leeb, Tetrahedron, 2004, 60, 11415-11420.
The bismuth and picolinic acid-catalyzed oxidation of alkyl arenes with tert-butyl hydroperoxide in pyridine and acetic acid gave benzylic ketones in good yields. Alternatively, oxidation of methyl arenes gave the corresponding substituted benzoic acids. A radical mechanism is discussed.
Y. Bonvin, E. Callens, I. Larrosa, D. A. Henderson, J. Oldham, A. J. Burton, A. G. M. Barrett, Org. Lett., 2005, 7, 4549-4552.
Autoxidative sp3 C-H transformation of diarylmethanes in the presence of oxygen mediated by t-BuONa provides diaryl ketones in very good yields under mild reaction conditions, without transition metal catalysts or additional chemical oxidants.
J.-S. Li, F. Yang, Q. Yang, Z.-W. Li, Z.-Q. Chen, Y.-D. Da, P.-M. Huang, C. Chen, Y. Zhang, L-Z. Huang, Synlett, 2017, 28, 994-998.
CrO3 is an efficient catalyst for benzylic oxidation with periodic acid as the terminal oxidant in acetonitrile. Substituted electron-poor toluenes and diarylmethanes were oxidized to the corresponding substituted benzoic acids and ketones in excellent yields. Benzyl ethers such as isochroman and phthalan were converted to 3,4-dihydroisocoumarin and phthalide in quantitative yields.
S. Yamazaki, Org. Lett., 1999, 1, 2129-2132.
Aryl radicals generated in situ from arene diazonium fluoroborates promoted by ascorbic acid enable a convenient and general oxidative arylation of vinyl arenes in air at room temperature in the absence of any additive and visible light irradiation. Various 2-aryl acetophenones have been obtained in good yields.
B. Majhi, D. Kundu, B. C. Ranu, J. Org. Chem., 2015, 80, 7739-7745.
A metal-free and green catalytic system enables an oxyfluorination of olefins for the synthesis of α-fluoroketones which is an important building block for organic synthesis. Moreover, this reaction system exhibits great functional group tolerance.
Q. Yang, L.-L. Mao, B. Yang, S.-D. Yang, Org. Lett., 2014, 16, 3460-3463.
Reactivity at the homobenzylic position can be accomplished using dual organic photoredox/cobalt catalysis. Through a two-part catalytic system, alkyl arenes undergo dehydrogenation followed by an anti-Markovnikov Wacker-type oxidation to provide benzyl ketone products. This formal homobenzylic oxidation is accomplished with high atom economy without the use of directing groups.
J. B. McManus, J. D. Griffin, A. R. White, D. A. Nicewicz, J. Am. Chem. Soc., 2020, 142, 10325-10330.