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Synthesis of hydroxy ketones, esters, nitriles and related compounds

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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.

An enantiomerically pure (camphorsulfonyl)oxaziridine enables a reagent-controlled asymmetric oxidation of tri- and tetrasubstituted ketone enolate anions. Whereas the stereoselectivities for trisubstituted enolates are very good, those for tetrasubstituted enolates are lower.
F. A. Davis, A. C. Sheppard, B. C. Chen, M. S. Haque, J. Am. Chem. Soc., 1990, 112, 6679-6690.

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.

The combination of electrochemical synthesis and aerobic oxidation enables a transition-metal-free dioxygenation of alkenes to provide α-oxygenated ketones in an eco-friendly fashion. A wide range of alkenes and N-hydroxyimides provided α-oxygenated ketones in good yields.
C. Dai, Y. Shen, Y. Wei, P. Liu, P. Sun, J. Org. Chem., 2021, 86, 13711-13719.

Treatment of α-iodocarboxylic acid derivatives with 2 equiv of triethylborane under oxygen atmosphere gives the corresponding α-hydroxy acid derivatives. Tertiary iodides and substrates sensitive to nucleophiles are efficiently converted to alcohols.
N. Kihara, C. Ollivier, P. Renaud, Org. Lett., 1999, 1, 1419-1422.

Methyltrioxorhenium (MTO) catalyzes an oxidation of methyl trimethylsilyl ketene acetals with urea hydrogen peroxide to afford α-hydroxy and α-siloxy esters. On treatment with potassium fluoride, the α-hydroxy esters are obtained in high yields.
S. Stanković, J. H. Espenson, J. Org. Chem., 2000, 65, 5528-5530.

α-Oxidation of a variety of carboxylic acids, which preferentially undergo undesired decarboxylation under radical conditions, proceeded efficiently under optimized conditions via a chemoselective enolization without stoichiometric amounts of Brønsted base. The formed redox-active heterobimetallic enediolate efficiently coupled with free radical TEMPO.
T. Tanaka, R. Yazaki, T. Ohshima, J. Am. Chem. Soc., 2020, 142, 4517-4524.

By rendering the α-position of amides electrophilic through a mild and chemoselective umpolung transformation, a broad range of widely available oxygen, nitrogen, sulfur, and halogen nucleophiles can be used to generate α-functionalized amides.
C. R. Gonçalves, M. Lemmerer, C. J. Teskey, P. Adler, D. Kaiser, B. Maryasin, L. González, N. Maulide, J. Am. Chem. Soc., 2019, 141, 18437-18443.

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.

The combination of achiral dirhodium complexes and chiral phosphoric acids or chiral phosphoramides enables highly enantioselective O-H bond insertion reactions between water and α-alkyl- and α-alkenyl-α-diazoesters as carbene precursors. This protocol represents an efficient new method for preparation of multifunctionalized chiral α-alkyl and α-alkenyl hydroxyl esters.
Y. Li, Y.-T. Zhao, T. Zhou, M.-Q. Chen, Y.-P. Li, M.-Y. Huang, Z.-C. Xu, S.-F. Zhu, Q.L. Zhou, J. Am. Chem. Soc., 2020, 142, 10557–10566.

Functionalization of carboxylic acids with sulfoxonium ylides in the presence of [VO(acac)₂] provides α-carbonyloxy esters in good yield. Diazo compounds as usual carbene source failed.
F. F. Koothradan, A. S. Babu, K. P. Pushpakaran, A. Jayarani, C. Sivasankar, J. Org. Chem., 2022, 87, 10564-10575.

Nonbenzenoid aromatic carbocation can be used as organic Lewis acid catalysts in O-H functionalization reactions of diazoalkanes with benzoic acids. The reported protocol with tropylium is applicable to a wide range of diazoalkanes and carboxylic acids with excellent efficiency.
C. Empel, T. V. Nguyen, R. M. Koenigs, Org. Lett., 2021, 23, 548-553.

A catalytic, metal-free O-H bond insertion of α-diazoesters in water in the presence of a catalytic amount of B(C₆F₅)₃ provides a series of α-hydroxyesters in very good yields.
H. H. San, S.-J. Wang, M. Jiang, X.-Y. Tang, Org. Lett., 2018, 20, 4672-4676.

A Ag₂O-catalyzed reaction of carboxylic acids, ynol ethers, and m-CPBA provides α-carbonyloxy esters via formation of three C-O bonds. The protocol offers use of readily available starting materials and broad substrate scope.
L. Zeng, H. Sajiki, S. Cui, Org. Lett., 2019, 21, 6423-6426.

Despite the high reactivity of alkoxyl (RO·) radicals and their propensity to easily undergo β-scission or Hydrogen Atom Transfer (HAT) reactions, an efficient photoredox-mediated intermolecular trapping of alkoxyl radicals by silyl enol ethers enables the introduction of both structurally simple and more complex alkoxy groups into a wide range of ketones and amides.
C. Banoun, F. Bourdreux, E. Magnier, G. Dagousset, Org. Lett., 2021, 23, 8921-8925.

The use of chiral α-alkyl N-tert-butanesulfinyl imidates and α-aryl N′-tert-butanesulfinyl amidines enables a diastereoselective α-hydroxylation using molecular oxygen. The aza-enolates generated from deprotonation of the imidates/amidines react with O₂ followed by transformation into α-hydroxylation products in the presence of trimethyl phosphite as reductant.
P.-J. Ma, H. Liu, Y.-J. Xu, H. A. Aisa, C.-D. Lu, Org. Lett., 2018, 20, 1236-1239.

A copper-catalyzed oxy-aminomethylation reaction of diazo compounds with readily available N,O-acetals provides α-hydroxy-β²-amino acid derivatives with quaternary carbon centers in good yields.
J. Yu, L. Chen, J. Sun, Org. Lett., 2019, 21, 1664-1667.

A cooperative primary amine and ketone dual catalytic approach enables the asymmetric α-hydroxylation of β-ketocarbonyls with H₂O₂ in excellent yield and enantioselectivity. Notably, late-stage hydroxylation for peptidyl amide or chiral esters can also be achieved with high stereoselectivity.
M. Cai, K. Xu, Y. Li, Z. Nie, L. Zhang, S. Luo, J. Am. Chem. Soc., 2021, 143, 1078-1087.

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.

A highly efficient direct α-acyloxylation of 1,3-dicarbonyl compounds with carboxylic acids is mediated by iodosobenzene. The reaction of various 1,3-dicarbonyl compounds with carboxylic acids provides the corresponding α-acyloxylated products in good to excellent yields under mild reaction conditions. The loading sequence of reactants and oxidant is crucial for the generation of the active species.
C. B. Rao, J. Yuan, Q. Zhang, R. Zhang, N. Zhang, J. Fang, D. Dong, J. Org. Chem., 2018, 83, 2904-2911.

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 electrochemically induced cross-dehydrogenative coupling of β-diketones and β-ketoesters with carboxylic acids provides intermolecular C-O coupling products in high yields using DMSO as a solvent in an undivided cell equipped with carbon and platinum electrodes at high current density. Electric current acts as a stoichiometric oxidant.
O. V. Bityukov, O. K. Matveeva, V. A. Vil', V. A. Kokorekin, G. I. Nikishin, A. O. Terent'ev, J. Org. Chem., 2019, 84, 1448-1460.

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.

A cyanide-catalyzed ring-expansion of cyclic α-hydroxy-β-oxoesters provides δ-valerolactone derivatives in up to quantitative yields. Several alkyl-substituted as well as benzo- and heteroarene-annulated starting materials are converted without problems. As an additional benefit, the substrates are straightforwardly accessed by cerium-catalyzed aerobic α-hydroxylation of readily available β-oxoesters.
D. Kieslich, J. Christoffers, Org. Lett., 2021, 23, 953-957.

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 (S_N2), wheareas hydroxide prefers γ-substitution with stereoselective allylic transposition (S_N2'). Regioselectivity with alkoxides depends upon alkene substitution.
J. L. Shamshina, T. S. Snowden, Org. Lett., 2006, 8, 5881-5884.

The arylthiolated Au₂₅(F-Ph)₁₈^- nanocluster is synthesized and characterized. Ligands avoid distortion of the geometric structure, limit the Jahn-Teller effect, and protect the nanocluster from oxidization. The low energy gap (HOMO-LUMO) of the synthetic clusters enables photocatalytic oxidative functionalization reactions mediated by near-infrared light (850 nm).
S. Wang, L. Tang, B. Cai, Z. Yin, Y. Li, L. Xiong, X. Kang, J. Xuan, Y. Pei, M. Zhu, J. Am. Chem. Soc., 2022, 144, 3787-3792.

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.

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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.