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Synthesis of hydroxy ketones and related compounds


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Rubottom Oxidation

Recent Literature

A direct asymmetric benzoyloxylation of aldehydes with benzoyl peroxide catalyzed by (S)-2-(triphenylmethyl)pyrrolidine provides optically active α-benzoyloxyaldehydes as useful chiral building blocks.
T. Kano, H. Mii, K. Maruoka, J. Am. Chem. Soc., 2009, 131, 3450-3451.

Oxidation of alkyl aryl ketones in the presence of Oxone, trifluoroacetic anhydride and a catalytic amount of iodobenzene affords α-hydroxyalkyl aryl ketones in good yield. This method provides an effective and economical entry for the α-hydroxylation of ketones.
C. Chen, X. Feng, G. Zhang, Q. Zhao, G. Huang, Synthesis, 2008, 3205-3208.

An unprecedented α-hydroxylation strategy using inexpensive N,N-dimethylformamide (DMF) as an oxygen source enables the synthesis of α-hydroxy arones. This reaction provides an alternative strategy for the α-hydroxylation of arones.
W. Liu, C. Chen, P. Zhou, J. Org. Chem., 2017, 82, 2219-2222.

In an efficient α-hydroxylation of carbonyls compounds, readily available I2 or NBS was used as catalyst and DMSO as terminal oxidant. The reaction is mild, less toxic, easy to perform and allows the conversion of a diverse range of tertiary as well as secondary Csp3-H bonds.
Y.-F. Liang, K. Wu, S. Song, X. Li, X. Huang, N. Jiao, Org. Lett., 2015, 17, 876-879.

Various ketones could be reacted into α-tosyloxy ketones in the presence of MCPBA, PTSA•H2O, catalytic amounts of iodine and tert-butylbenzene in a mixture of acetonitrile and 2,2,2-trifluoroethanol. In the reaction, 4-tert-butyl-1-iodobenzene is formed at first and then converted into the α-tosyloxylation reagent 4-tert-butyl-1-[(hydroxy)(tosyloxy)iodo]benzene by the reaction with MCPBA and PTSA•H2O.
A. Tanaka, K. Moriyama, H. Togo, Synlett, 2011, 1853-1854.

The reactivity of iodoarene amide catalysts in the α-oxytosylation of propiophenone is influenced by steric and electronic properties. A very reactive meta-substituted benzamide catalyst was employed in the α-oxytosylation of a series of substituted propiophenones to provide α-tosyloxy ketones in excellent isolated yield.
T. R. Lex, M. I. Swasy, D. C. Whitehead, J. Org. Chem., 2015, 80, 12234-12243.

Various α-tosyloxyketones were efficiently prepared in high yields from the reaction of ketones with m-chloroperbenzoic acid and p-toluenesulfonic acid in the presence of a catalytic amount of iodobenzene.
Y. Yamamoto, H. Togo, Synlett, 2006, 798-800.

α-Tosyloxyketones and α-tosyloxyaldehydes were directly prepared from alcohols by treatment with iodosylbenzene and p-toluenesulfonic acid monohydrate in good yields. Modified methods gave thiazoles, imidazoles and imidazo[1,2-a]pyridines from alcohols in good to moderate yields.
M. Ueno, T. Nabana, H. Togo, J. Org. Chem., 2003, 68, 6424-6426.

α-Acetoxylation of ketones catalyzed by iodobenzene using acetic anhydride and 30% aqueous hydrogen peroxide as the oxidant is an effective and economical method for the preparation of α-acetoxy ketones in good yields.
J. Sheng, Y. Li, M. Tang, B. Gao, G. Huang, Synthesis, 2007, 1165-1168.

Dess-Martin periodine in combination with organosulfonic acids reacted with ketones and dicarbonyl compounds under reflux temperature in acetonitrile to give α-organosulfonyloxylated compounds in good yields.
U. S. Mahajan, K. G. Akamanchi, Synlett, 2008, 987-990.

Enol esters were rapidly converted in high yields to their corresponding α-tosyloxy ketones in the presence of [hydroxy(tosyloxy)iodo]benzene (HTIB). Aromatic, aliphatic, and cyclic enol esters were found to be suitable substrates for the reaction.
B. Basdevant, C. Y. Legault, J. Org. Chem., 2015, 80, 6897-6902.

Bench stable N-Methyl-O-alkoxyformate hydroxylamine hydrochloride reagents can be prepared in two high-yielding steps from N-Boc-N-methyl hydroxyl­amine. Subsequent reaction with various carbonyl compounds give the corresponding α-functionalised products in good yield via a proposed [3,3]-sigmatropic rearrangement.
A. Hall, K. L. Jones, T. C. Jones, N. M. Killeen, R. Pörzig, P. H. Taylor, S. C. Yau, N. C. O. Tomkinson, Synlett, 2006, 3435-3438.

A palladium-catalyzed, environmentally friendly dioxygenation reaction of simple alkenes enables a rapid assembly of valuable α-hydroxy ketones with high atom economy.
J. Huang, J. Li, J. Zheng, W. Wu, W. Hu, L. Ouyang, H. Jiang, Org. Lett., 2017, 19, 3354-3357.

Gold-catalyzed intermolecular oxidation enables an efficient conversion of various terminal alkynes into the corresponding α-acetoxy ketones in the presence of 8-methylquinoline 1-oxide as the oxidant. The reaction probably proceeds through an α-oxo gold carbene intermolecular O-H insertion.
C. Wu, Z. Liang, D. Yan, W. He, J. Xiang, Synthesis, 2013, 45, 2605-2611.

Phenyliodonium diacetate mediates a synthesis of α-oxygenated ketones from styrenes in the presence of molecular oxygen and N-hydroxyphthalimide or N-hydroxybenzotriazole under metal-free conditions. The present method is applicable for wide range of styrenes with various functional groups.
S. Samanta, R. R. Donthiri, C. Ravi, S. Adimurthy, J. Org. Chem., 2016, 81, 3457-3463.

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 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.

The direct asymmetric α-benzoyloxylation of β-ketocarbonyls catalyzed by a chiral primary amine demonstrates excellent enantioselectivity for a broad range of substrates, which allows convenient access to highly enantioenriched α-hydroxy-β-ketocarbonyls.
D. Wang, C. Xu, L. Zhang, S. Luo, Org. Lett., 2015, 17, 576-579.

An I2-catalyzed hydroxylation of β-dicarbonyl moieties using air as the oxidant under photoirradiation gives α-hydroxy-β-dicarbonyl compounds. With α-unsubstituted malonates, the hydroxylated dimerization product was afforded as the predominant product along with a minor product, α,α-dihydroxyl malonate.
C.-B. Miao, Y.-H. Wang, M.-L. Xing, X.-W. Lu, X.-Q. Sun, H.-T. Yang, J. Org. Chem., 2013, 78, 11584-11589.

An efficient method for the 2-hydroxylation of 1,3-diketones by using inexpensive atmospheric oxygen as an oxidant under transition-metal-free and ecofriendly conditions provides products in high yields.
Z. Li, T. Li, J. Li, L. He, X. Jia, J. Yang, Synlett, 2015, 26, 2863-2865.

β-Ketoesters can directly be transformed to the corresponding α-hydroxymalonic esters, tartronic esters, with molecular oxygen catalyzed by calcium iodide under visible light irradiation from a fluorescent lamp. This convenient tandem oxidation/rearrangement reduces consumption of energy, time, and solvents.
N. Kanai, H. Nakayama, N. Tada, A. Itoh, Org. Lett., 2010, 12, 1948-1951.

The α-hydroxylation of α-alkynyl carbonyl compounds using IBX (o-iodoxybenzoic acid) gave various tertiary alcohols without dehydrogenation products under mildly acidic conditions.
S. F. Kirsch, J. Org. Chem., 2005, 70, 10210-10212.

S. F. Kirsch, J. Org. Chem., 2005, 70, 10210-10212.

Mn(OAc)3 based regioselective oxidation of various 2-cyclopentenone, 2-cyclohexenone and aromatic ketone derivatives in benzene afforded the corresponding tertiary α'-acetoxy oxidation products in good yields.
C. Tanyeli, C. Iyiguen, Tetrahedron, 2003, 59, 7135-7139.

A new mild RuO4-catalyzed ketohydroxylation of olefins is reported. α-Hydroxy ketones were obtained with high regioselectivity and in good to excellent yields.
B. Plietker, J. Org. Chem., 2003, 68, 7123-7125.

The reaction of alkenyl trichloromethyl carbinols with various nucleophiles under protic basic conditions reveals that mercaptans participate by α-substitution (SN2), wheareas hydroxide prefers γ-substitution with stereoselective allylic transposition (SN2'). Regioselectivity with alkoxides depends upon alkene substitution.
J. L. Shamshina, T. S. Snowden, Org. Lett., 2006, 8, 5881-5884.

A chiral (1S,2S)-cyclohexanediamine backbone salen-zirconium(IV) complex as the catalyst enables a highly enantioselective α-hydroxylation of β-keto esters using cumene hydroperoxide (CHP) as the oxidant to provide chiral α-hydroxy β-keto esters in excellent yields and enantioselectivities. The zirconium catalyst is recyclable and the reaction can be performed in gram scale.
F. Yang, J. Zhao, X. Tang, G. Zhou, W. Song, Q. Meng, Org. Lett., 2017, 19, 448-451.


A new and efficient chiral catalyst system, lanthanum-chiral BINOL-tris(4-fluorophenyl)phosphine oxide-cumene hydroperoxide, was developed for the epoxidation of α,β-unsaturated ketones, thus providing the corresponding epoxy ketones with excellent enantioselectivities (up to >99% ee) in good to excellent yields at room temperature.
R. Kino, K. Daikai, T. Kawanami, H. Furuno, J. Inanaga, Org. Biomol. Chem., 2004, 2, 1822-1824.