Categories: C-O Bond Formation > Synthesis of alcohols (hydroxylation) >
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 (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.
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.
Related
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.
