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Synthesis of epoxides


Name Reactions

Jacobsen-Katsuki Epoxidation

Prilezhaev Reaction

Sharpless Epoxidation

Shi Epoxidation

Recent Literature

2,2,2-trifluoroacetophenone is an efficient organocatalyst for a cheap, mild, fast, and environmentally friendly epoxidation of alkenes. Various olefins, mono-, di-, and trisubstituted, are epoxidized chemoselectively in high to quantitative yields utilizing low catalyst loadings and H2O2 as a green oxidant.
D. Limniois, C. G. Kokotos, J. Org. Chem., 2014, 79, 4270-4276.

Trifluoroacetone catalyzes a mild and operationally simple epoxidation of various alkens in good yields using hydrogen peroxide as primary oxidant at high pH. The use of H2O2 as oxidant significantly reduces the amount of solvent and salts introduced.
L. Shu, Y. Shi, J. Org. Chem., 2000, 65, 8807-8810.

An effective epoxidation of lipophilic alkenes using hydrogen peroxide was accomplished with a manganese sulfate/bicarbonate catalytic system in an ionic liquid at room temperature.
K.-H. Tong, K.-Y. Wong, T. H. Chan, Org. Lett., 2003, 5, 3423-3425.

Methyltrioxorhenium (MTO) catalyzes an epoxidation of alkenes with 30% aqueous hydrogen peroxide. The addition of 1-10 mol % of 3-cyanopyridine increases the system's efficiency resulting in high isolated yields of the corresponding epoxides. Alkenes yielding epoxides more sensitive to nucleophilic ring opening require a mixture of 3-cyanopyridine and pyridine.
H. Adolfsson, C. Copéret, J. P. Chiang, A. K. Yudin, J. Org. Chem., 2000, 65, 8651-8658.

Organometallic rhenium species (e.g., CH3ReO3) can be replaced by less expensive inorganic rhenium oxides (e.g., Re2O7, ReO3(OH), and ReO3) using bis(trimethylsilyl) peroxide (BTSP) as oxidant in place of aqueous H2O2. Using a catalytic amount of a proton source, controlled release of hydrogen peroxide helps preserve sensitive peroxorhenium species and enables catalytic turnover to take place.
A. K. Yudin, J. P. Chiang, H. Adolfsson, C. Copéret, J. Org. Chem., 2000, 65, 4713-4718.

In MTO-catalyzed epoxidation, aqueous hydrogen peroxide is typically added dropwise to a dichloromethane solution of the olefin, pyrazole as accelerant, and MTO. The use of sodium percarbonate (SPC) offers a slow release of hydrogen peroxide, that can be accelerated using trifluoroacetic acid.
A. R. Vaino, J. Org. Chem., 2000, 65, 4210-4212.

The complex [MnII(R,R-mcp)(CF3SO3)2] is a very efficient and practical catalyst for the epoxidation of a wide scope of olefins including terminal, tertiary, cis and trans internal, enones, and methacrylates using peracetic acid as the terminal oxidant.
A. Murphy, G. Dubois, T. D. P. Stack, J. Am. Chem. Soc., 2003, 125, 5250-5251.

A bench-stable, solid triazine-based oxidizing reagent, 2-hydroperoxy-4,6-diphenyl-1,3,5-triazine (Triazox) can be synthesized from inexpensive starting materials. This reagents has been used for epoxidation of alkenes possessing acid-sensitive functionalities in good to excellent yields. The accompanying nonacidic triazinone coproduct can be easily removed by filtration.
K. Yamada, Y. Igarashi, T. Betuyaku, M. Kitamura, K. Hirata, K. Hioki, M. Kunishima, Org. Lett., 2018, 20, 2015-2019.

An in situ generated catalyst system based on Mn(CF3SO3)2, picolinic acid, and peracetic acid converts a broad scope of olefins to epoxides at 0 °C in <5 min. The reaction offers remarkable oxidant efficiency.
R. A. Moretti, J. Du Bois, T. D. P. Stack, Org. Lett., 2016, 18, 2528-2531.

Bubbling SO2F2 gas into a solution of olefin, 30% aqueous hydrogen peroxide, and 2 M aqueous potassium carbonate in 1,4-dioxane at room temperature for 1 h provides the corresponding epoxides in good to excellent yields. This inexpensive, mild, and highly efficient epoxidizing system is suitable to a variety of olefinic substrates including electron-rich and electron-deficient ones.
C. Ai, F. Zhu, Y. Wang, Z. Yan, S. Lin, J. Org. Chem., 2019, 84, 11928-11934.

An efficient epoxidation of a broad range of olefins using hydrogen peroxide as the oxidant has been accomplished in the presence of acetic acid and a manganese catalyst that exhibits an uncommon chemoselectivity.
I. Garcia-Bosch, X. Ribas, M. Costas, Adv. Synth. Catal., 2008, 351, 348-352.

A manganese catalyst containing a tetradentate ligand derived from triazacyclononane exhibits high catalytic activity in epoxidation reactions using peracetic acid as oxidant. The system exhibits broad substrate scope and is remarkably selective toward aliphatic cis-olefins. Mechanistic studies point toward an electrophilic oxidant delivering the oxygen atom in a concerted step.
I. Garcia-Bosch, A. Company, X. Fontrodona, X. Ribas, M. Costas, Org. Lett., 2008, 10, 2095-2098.

A non-heme iron complex catalyzes highly enantioselective epoxidation of olefins with H2O2 in the presence of catalytic amounts of carboxylic acid additives. Ligand and carboxylic acid synergistically cooperate in promoting efficient O-O cleavage and creating highly chemo- and enantioselective epoxidizing species which provide a broad range of epoxides in synthetically valuable yields and short reaction times.
O. Cussó, I. Garcia-Bosch, X. Ribas, J. Lloret-Fillol, M. Costas, J. Am. Chem. Soc., 2013, 135, 14871-14878.

An epoxidation of alkenes using hydrogen peroxide as the terminal oxidant is promoted by catalytic amounts (1.0-0.1 mol %) of manganese(2+) salts, and must be performed using at least catalytic amounts of bicarbonate buffer. Various aryl-substituted, cyclic, and trialkyl-substituted alkenes were epoxidized under these conditions using 10 equiv of hydrogen peroxide, but monoalkyl-alkenes were not. Additives such as sodium acetate and salicylic acid enhanced the rate of the desired epoxidation reaction by 2-3 times. Possible mechanisms for the reaction are discussed.
B. S. Lane, M. Vogt, V. J. DeRosa, K. Burgess, J. Am. Chem. Soc., 2002, 124, 11946-11954.

Enantioselective epoxidations of alkenes were achieved using a Shi-type carbohydrate-derived hydrate and Oxone. The chiral platform provided by the catalyst tolerates a wide range of substituents providing high yields and enantioselectivities. However, styrene derivatives were only converted with poor selectivities.
N. Nieto, I. J. Munslow, H. Fernández-Pérez, A. Vidal-Ferran, Synlett, 2008, 2856-2858.

Aryl benzyl selenoxides are efficient catalysts for the epoxidation of various olefinic substrates and the Baeyer-Villiger oxidation of aldehydes and ketones with hydrogen peroxide.
M. A. Goodman, M. R. Detty, Synlett, 2006, 1100-1104.

A tungsten-bishydroxamic acid complex promotes a simple, efficient, and environmentally friendly asymmetric epoxidation of allylic, and homoallylic alcohols at room temperature using aqueous hydrogen peroxide as oxidant.
C. Wang, H. Yamamoto, J. Am. Chem. Soc., 2014, 136, 1222-1225.

A new catalytic system for the asymmetric epoxidation of allylic alcohols has been developed featuring high enantioselectivity for Z olefins, catalyst loading of less than 1 mol%, reaction temperatures of 0°C to room temperature over a shorter time, use of aqueous tert-butyl hydroperoxide (TBHP) instead of anhydrous TBHP as an achiral oxidant, and simple workup procedures for small expoxy alcohols.
W. Zhang, A. Basak, Y. Kosugi, Y. Hoshino, H. Yamamoto, Angew. Chem. Int. Ed., 2005, 44, 4389-4391.

Chiral amino acid-based hydroxamic acids can be effective asymmetric catalysts for the epoxidation of allylic alcohols, especially disubstituted allylic alcohols. The mild reaction conditions, e.g., reasonable temperature, low degree of catalyst loading, and halogen-free solvent, extend the scope of this process.
Y. Hoshino, H. Yamamoto, J. Am. Chem. Soc., 2000, 122, 10452-10453.

Homoallylic alcohols were efficiently epoxidized to the corresponding 3,4-epoxy alcohols in excellent yields in the presence of methyltrioxorhenium (MTO) as catalyst, aqueous hydrogen peroxide as the terminal oxidant, and 3-methylpyrazole as an additive. Organic solvent-free conditions accelerate the reaction.
S. Yamazaki, J. Org. Chem., 2012, 77, 9884-9888.

Chiral bishydroxamic acid ligands provided good yields and high enantioselectivities in the vanadium-catalyzed asymmetric epoxidation of homoallylic alcohols.
W. Zhang, H. Yamamoto, J. Am. Chem. Soc., 2007, 129, 286-287.

Use of a solvent with greater density than the fluorous phase is an alternative to the U-tube method in phase-vanishing reactions in cases where both reactants are less dense than the fluorous phase.
N. K. Jana, J. G. Verkade, Org. Lett., 2003, 5, 3787-3790.

N. K. Jana, J. G. Verkade, Org. Lett., 2003, 5, 3787-3790.

A highly chemo- and enantioselective epoxidation of conjugated cis-enynes using readily available glucose-derived ketones as catalysts and Oxone as oxidant forms cis-propargyl epoxides in high ee's. The interaction between the alkyne substrate and the oxazolidinone moiety of the ketone catalyst are important for the stereodifferentiation.
C. P. Burke, Y. Shi, J. Org. Chem., 2007, 72, 4093-4097.

Highly enantio- and diastereoselective one-pot procedures for the synthesis of epoxy alcohols involve either asymmetric addition of an alkylzinc reagent to an enal or asymmetric vinylation of an aldehyde with divinylzinc reagents. Exposure of the reaction mixtures to dioxygen and addition of catalytic titanium tetraisopropoxide yields epoxy alcohols with good to excellent yields.
A. E. Lurain, A. Maestri, A. R. Kelli, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2004, 126, 13608-13609.

A. E. Lurain, A. Maestri, A. R. Kelli, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2004, 126, 13608-13609.

A series of 20 chiral epoxides were obtained with excellent yields and enantioselectivities within short reaction times using hybrid amide-based Cinchona alkaloids as catalysts at very low loading. Moreover, the catalyst solution can be reused 10times, without further catalyst addition to the reaction mixture.
M. Majdecki, A. Tyszka-Gumkowska, J. Jurczak, Org. Lett., 2020, 22, 8687-8691.

A simple and efficient enantioselective epoxidation of α,β-unsaturated ketones is catalyzed by rare-earth metal amides in the presence of phenoxy-functionalized chiral prolinols at room temperature using tert-butylhydroperoxide (TBHP) as the oxidant. The combination of an Yb-based amide and a chiral proligand provided chiral epoxides in excellent yields and enantiomeric excess of up to 99%.
C. Zeng, D. Yuan, B. Zhao, Y. Yao, Org. Lett., 2015, 17, 2242-2245.

An aerobic photoepoxidation of α,β-unsaturated ketones is driven by visible light in the presence of tetramethylguanidine (TMG), tetraphenylporphine (H2TPP), and molecular oxygen under mild conditions to provide α,β-epoxy ketones in good yields in 96 h. The reaction time can be shortened to 5 h using flow synthesis.
Y. Wu, G. Zhou, Q. Meng, X. Tang, G. Liu, H. Yin, J. Zhao, F. Yang, Z. Yu, Y. Luo, J. Org. Chem., 2018, 83, 13051-13062.

A chiral N,N'-dioxide/ScIII complex catalyzes an enantioselective epoxidation of α-substituted vinyl ketones in the presence of H2O2 as the oxidant to provide key epoxide intermediates for the synthesis of various triazole antifungal agents. The reaction proceeded efficiently in high yields and with good enantioselectivities.
Q. He, D. Zhang, F. Zhang, X. Liu, X. Feng, Org. Lett., 2021, 23, 6795-6800.

Using cinchona alkaloid-derived primary amines as catalysts and aqueous hydrogen peroxide as the oxidant, highly enantioselective Weitz-Scheffer-type epoxidation and hydroperoxidation reactions of α,β-unsaturated carbonyl compounds take place. Acyclic enones, cyclic enones, and α-branched enals can be converted. Intermediates have been characterized by MS and NMR. DFT calculations explain the activation of H2O2.
O. Lifchits, M. Mahlau, C. M. Reisinger, A. Lee, C. Farès, I. Polyak, G. Gopakumar, W. Thiel, B. List, J. Am. Chem. Soc., 2013, 135, 6677-6693.

Using cinchona alkaloid-derived primary amines as catalysts and aqueous hydrogen peroxide as the oxidant, highly enantioselective Weitz-Scheffer-type epoxidation and hydroperoxidation reactions of α,β-unsaturated carbonyl compounds take place. Acyclic enones, cyclic enones, and α-branched enals can be converted. Intermediates have been characterized by MS and NMR. DFT calculations explain the activation of H2O2.
O. Lifchits, M. Mahlau, C. M. Reisinger, A. Lee, C. Farès, I. Polyak, G. Gopakumar, W. Thiel, B. List, J. Am. Chem. Soc., 2013, 135, 6677-6693.

Heterobimetallic complexes stabilized by chiral phenoxy-functionalized prolinolate are highly active in catalyzing the epoxidation of α,β-unsaturated ketones, while the enantioselectivity varies according to the ionic radii of the rare earth center. A series of chalcone derivatives were converted to chiral epoxides in good ee at 0°C using TBHP as the oxidant.
Q. Qian, Y. Tan, B. Zhao, T. Feng, Q. Shen, Y. Yao, Org. Lett., 2014, 16, 4516-4519.

Visible-light-driven hydroacylations and epoxyacylations in water using methylene blue as photoredox catalyst and persulfate as oxidant deliver ketones and epoxyketones from a range of aromatic and aliphatic aldehydes as well as conjugated and nonconjugated olefins as abundant and inexpensive chemical feedstocks.
G. F. P. de Souza, J. A. Bonacin, A. G. Salles, Jr., J. Org. Chem., 2018, 83, 8331-8340.

Under the synergistic actions of photocatalyst Ru(bpy)3Cl2, tert-butyl hydroperoxide, cesium carbonate, and visible light irradiation, a range of styrenes and benzaldehydes smoothly form α,β-epoxy ketones via visible-light-enabled photocatalytic generation of acyl radicals as key intermediates.
J. Li, D. Z. Wang, Org. Lett., 2015, 17, 5260-5263.

Chiral primary amine salts catalyze highly enantioselective epoxidations of cyclic enones with hydrogen peroxide.
X. Wang, C. M. Reisinger, B. List, J. Am. Chem. Soc., 2008, 130, 6070-6071.

An asymmetric 1,2-addition of alkyl groups to conjugated cyclic enones gave allylic alcohols with chiral quaternary centers. The resultant allylic alcohols are converted into epoxy alcohols with excellent diastereoselectivities. A semipinacol rearrangement provided α,α-dialkyl-β-hydroxy ketones with all-carbon chiral quaternary centers.
S.-J. Jeon, P. J. Walsh, J. Am. Chem. Soc., 2003, 125, 9544-9545.

The catalytic asymmetric addition of alkyl groups to ketones under highly concentrated and solvent-free conditions permits reduction in catalyst loading by a factor of 2- to 40-fold compared with standard reaction conditions employing toluene and hexanes. Using cyclic conjugated enones, solvent-free asymmetric addition followed by a diastereoselective epoxidation using 5.5 M decane solution of tert-butyl hydroperoxide generated epoxy alcohols.
S.-J. Jeon, H. Li, P. J. Walsh, J. Am. Chem. Soc., 2005, 127, 16416-16425.

A chiral bisaryl-silyl-protected pyrrolidine acts as a very selective epoxidation organocatalyst using simple oxidation agents. The scope of the reaction is demonstrated by the formation of optically active α,β-epoxy aldehydes in high yields and enantioselectivities. The asymmetric epoxidation reactions proceed also under environmental friendly reaction conditions in, for example, water mixtures of alcohols.
M. Marigo, J. Franzen, T. B. Poulsen, W. Zhuang, K. A. Jorgensen, J. Am. Chem. Soc., 2005, 127, 6284-6289.

A catalytic asymmetric epoxidation reaction of various α,β-unsaturated esters via a conjugate addition of an oxidant using an yttirium-chiral biphenyldiol catalyst yielded the corresponding α,β-epoxy esters in up to 97% yield and 99% ee.
H. Kakei, R. Tsuji, T. Ohshima, M. Shibasaki, J. Am. Chem. Soc., 2005, 127, 8962-8963.

Promising, dual-functioning chiral catalysts for the highly enantioselective epoxidation of α,β-unsaturated ketones gave epoxy chalcones in excelllent yield and high enantioselectivity using 13% NaOCl as oxidizing agent in toluene under mild phase-transfer conditions.
T. Ooi, D. Ohara, M. Tamura, K. Maruoka, J. Am. Chem. Soc., 2004, 126, 6844-6845.

A highly enantioselective catalytic epoxidation of α,β-unsaturated diaryl enones was achieved with high chemical yield by using aqueous hydrogen peroxide in the presence of a guanidine-urea bifunctional organocatalyst. The catalyst performs cooperatively by interaction of the guanidine group with hydrogen peroxide and the urea group with the enone or vice versa.
S. Tanaka, K. Nagasawa Synlett, 2009, 667-670.

The epoxidation of trans-chalcones proceeds under mild conditions at room temperature in alkaline solution to afford the corresponding epoxides in excellent yields using trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane as an efficient oxygen source.
D. Azarifar, K. Khosravi, Synlett, 2010, 2755-2758.

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.

1-Trifluoroboratoalkenes are oxidized by dioxirane, providing air-stable, crystalline oxiranyltrifluoroborates without cleavage of the carbon-boron bond. The first Suzuki-Miyaura coupling of an epoxytrifluoroborate has been accomplished.
G. A. Molander, M. Ribagorda, J. Am. Chem. Soc., 2003, 125, 11148-11149.