Categories: C=C Bond Formation >
Synthesis of enones
Allyl-nickel catalysis enables α,β-dehydrogenation of carbonyl compounds. In addition, an oxidative cycloalkenylation reaction provides access to bicycloalkenones with fused, bridged, and spirocyclic ring systems using unactivated ketone and alkene precursors.
D. Huang, S. M. Szewczyk, P. Zhang, T. R. Newhouse, J. Am. Chem. Soc., 2019, 141, 5669-5674.
A Julia-Kocienski reaction of 2,2-dimethoxyethyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfone with various aldehydes, followed by acid hydrolysis in one pot, provides (E)-α,β-unsaturated aldehydes in a short time and with high yields.
K. Ando, H. Watanabe, X. Zhu, J. Org. Chem., 2021, 86, 6969-6973.
An iron-catalyzed α,β-dehydrogenation of carbonyl compounds converts a broad range of aldehydes, ketones, lactones, lactams, amines, and alcohols to their α,β-unsaturated counterparts in a simple one-step reaction with high yields.
X.-W. Zhang, G.-Q. Jiang, S.-H. Lei, X.-H. Shan, J.-P. Qu, Y.-B. Kang, Org. Lett., 2021, 23, 1611-1615.
A highly efficient and practical Pd(II)/Cu(OAc)2 catalyzed Saegusa oxidation converts enol ethers to the corresponding enals at extremely low catalyst loadings under ligand-free and aqueous conditions. Its synthetic utility was demonstrated with a number of diverse substrates and large-scale applications.
Q. Zhu, Y. Luo, Y. Guo, Y. Zhang, Y. Tao, J. Org. Chem., 2021, 86, 5463-5476.
A triphenylphosphine oxide catalyzed reductive halogenation of an α,β-unsaturated ketone with trichlorosilane as the reducing reagent and an N-halosuccinimide as the electrophilic halogen source enables a selective synthesis of unsymmetrical α-haloketones.
Z. Lao, H. Zhang, P. H. Toy, Org. Lett., 2019, 21, 8149-8152.
A simple and efficient method converts aldehydes into α,β-unsaturated aldehydes with a two-carbon homologation. Hydroboration of ethoxy acetylene with BH3 • SMe2 generates tris(ethoxyvinyl) borane. Transmetalation with diethylzinc, addition to aldehydes or ketones, and acidic workup affords enals or protected derivatives depending on the workup procedure.
P. Valenta, N. A. Drucker, J. W. Bode, P. J. Walsh, Org. Lett., 2009, 11, 2117-2119.
Two optimal catalytic systems for the convenient and fast α-methylenation of aldehydes with aqueous formaldehyde are described that allow short reaction times and afford the methylenated products in good to excellent yields and chemoselectivity.
A. Erkkilä, P. M. Pihko, J. Org. Chem., 2006, 71, 2538-2541.
An I(III)-mediated skeletal reorganization of silyl enol ethers enables a formal enone α-arylation. This metal-free transformation offeres mild conditions, good yields, and high stereoselectivities for β-substituted enones.
B. S. Martins, D. Kaiser, A. Bauer, I. Tiefenbrunner, N. Maulide, Org. Lett., 2021, 23, 2094-2098.
A one-pot procedure enables the conversion of various ketones into α,β-unsaturated ketones in very good yields under mild conditions via treatment of lithium enolates with N-tert-butyl phenylsulfinimidoyl chloride.
T. Mukaiyama, J.-i. Matsuo, H. Kitagawa, Chem. Lett., 2000, 1250-1251.
Regioselective C-C bond fragmentation of cyclopropanes followed by desulfonylation enables a one-step strategy for the synthesis of α-methenyl ketones from β-keto sufones. Success of the methodology is elaborated for the synthesis of chromanones and isoflavanones in one-step.
G. Pandey, J. Vaitla, Org. Lett., 2015, 17, 4890-4893.
The application of the 1-butyl-3-methylimidazolium-based ionic liquid [BMIM][NTf2] as solvent enabled clean α-methylenations of carbonyl compounds in a short time and good yields. This ionic liquid was reused without affecting the reaction rates or yields over seven runs.
J. A. Vale, D. F. Zanchetta, P. J. S. Moran, J. A. R. Rodrigues, Synlett, 2009, 75-78.
Gold catalysis enables a chemoselective α-methylenation of aromatic ketones using Selectfluor as a methylenating agent to provide various 1,2-disubstituted propenone derivatives in good yields. This reaction offers simple operation, good functional group tolerance, and broad scope of substrates.
H. Zhu, X. Meng, Y. Zhang, G. Chen, Z. Cao, X. Sun, J. You, J. Org. Chem., 2017, 82, 12059-12065.
A one-step reaction of trisubstituted olefins provides enones in good yields with high regioselectivity under visible-light irradiation in the presence of molecular oxygen and a photocatalyst. The reaction tolerates oxygen- and nitrogen-containing functional groups, heteroaromatic rings, and cyclopropanes.
S. Harada, D. Matsuda, T. Morikawa, A. Nishida, Synlett, 2020, 31, 1372-1377.
Various aryl ketone derivatives react readily with DMSO under transition metal-free reaction condition, producing the α,β-unsaturated carbonyl compounds in good yields. This direct α-Csp3-H methylenation offers wide substrate scope and provides an efficient and expeditious approach to an important class of α,β-unsaturated carbonyl compounds.
Y.-F. Liu, P. Yi Ji, J.-W. Xu, Y.-Q. Hu, Q. Liu, W.-P. Luo, C.-C. Guo, J. Org. Chem., 2017, 82, 7161-7164.
A phosphorous acid promoted alkyne-aldehyde hydration-condensation enables a simple and environmentally benign synthesis of chalcones in high to excellent yields in an oil/water two-phase system.
Y. Zhou, Z. Li, X. Yang, X. Chen, M. Li, T. Chen, S.-F. Yin, Synthesis, 2016, 48, 231-237.
The combination of a copper-catalyzed oxidation in the presence of oxygen, a deprotonation, and a Wittig reaction enables the synthesis of α,β-unsaturated esters, ketones, and nitriles from alcohols and functionalized phosphonium salts. The solvent mixture of acetonitrile and formamide (1:1) is optimized for all part reactions.
W. Ding, J. Hu, H. Jin, X. Yu, S. Wang, Synthesis, 2018, 50, 107-118.
The combination of cerium(III) chloride heptahydrate with sodium iodide mediates a useful dehydration of β-hydroxy ketones and β-hydroxy esters to the corresponding α,β-unsaturated derivatives in refluxing acetonitrile. This method, which uses cheap and friendly reagents, provides the corresponding (E)-isomers in good yields as the only isolable products.
G. Bartoli, M. C. Bellucci, M. Petrini, E. Marcantoni, L. Sambri, E. Torregiani, Org. Lett., 2000, 2, 1791-1793.
A sequential PdCl2/CrO3-promoted Wacker process followed by an acid-mediated dehydration enables the synthesis of β-substituted and β,β-disubstituted α,β-unsaturated methyl ketones from homoallyl alcohols with a terminal double bond, whereas internal homoallyl alcohols delivered regioselectively nonconjugated unsaturated carbonyl compounds under the same protocol.
V. Bethi, R. A. Fernandes, J. Org. Chem., 2016, 81, 8577-8584.
A sequential nucleophilic addition of lithio-trimethylsilylmethylphosphonate to an acyl fluoride followed by generation of a lithio-β-ketophosphonate by desilylation and a Horner-Wadsworth-Emmons reaction of an aldehyde took place cleanly in a one-pot operation. Various E- and Z-enones were obtained in high yields with high stereoselectivities by this one-pot procedure.
T. Umezawa, T. Seino, F. Matsuda, Org. Lett., 2012, 14, 4206-4209.
A domino oxidation of primary alcohols gives α,β-unsaturated compounds using the combination of PCC-NaOAc and stabilized Wittig reagents.
J. Shet, V. Desai, S. Tilve, Synthesis, 2004, 1859-1863.
Water is an effective medium for the Wittig reaction over a wide range of stabilized ylides and aldehydes including especially substrates with large hydrophobic entities. Despite sometimes poor solubility of the reactants, good yields and high E-selectivities are achieved, and the rate of the reactions in water is unexpectedly accelerated.
A. El-Batta, C. Jiang, W. Zhao, R. Anness, A. L. Cooksy, M. Bergdahl, J. Org. Chem., 2007, 72, 5244-5259.
A Ba/Pd cooperative catalysis system enables a dehydrative cross-coupling of allylic alcohols with P-ylides followed by a Wittig reaction in one pot. Various multisubstituted 1,4-dienes were isolated in very good yields with a broad range of P-ylides and aldehydes with excellent E selectivity.
P. Xie, W. Fu, X. Cai, Z. Sun, Y. Wu, S. Li, C. Gao, X. Yang, T.-P. Loh, Org. Lett., 2019, 21, 7055-7059.
Ketone-stabilized phosphonium ylides were allylated with high regioselectivity by primary allylic amines in the presence of 5 mol % Pd(PPh3)4 and 10 mol % B(OH)3. A subsequent one-pot Wittig olefination gave structurally diverse α,β-unsaturated ketones in good to excellent overall yields. Ester- and nitrile-stabilized phosphonium ylides can be converted if B(OH)3 is replaced with TsOH.
X.-T. Ma, Y. Wang, R.-H. Dai, C.-R. Liu, S.-K. Tian, J. Org. Chem., 2013, 78, 11071-11075.
A highly efficient α alkylation of ketones with primary alcohols by the use of a recyclable palladium catalyst has been demonstrated.
M. S. Kwon, N. Kim, S. H. Seo, I. S. Park, R. K. Cheedrala, J. Park, Angew. Chem. Int. Ed., 2005, 42, 6913-6915.
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.
A mild oxidation of alkyl enol ethers to enals employs low loadings of a palladium catalyst and tolerates a diverse array of functional groups, while allowing the formation of di-, tri-, and tetrasubtituted olefins. The application of this methodology to intramolecular reactions of alkyl enol ethers containing pendant alcohols provides furan and 2,5-dihydrofuran products.
M. G. Lauer, W. H. Henderson, A. Awad, J. P. Sambuli, Org. Lett., 2012, 14, 6000-6003.
(PCy3)2Cl2Ru=CHPh-catalyzed Kharasch additions of trihaloalkanes across olefins provide polyhalogenated adducts, which upon hydrolysis furnish α,β-unsaturated ketones, aldehydes, or γ-hydroxybutenolides. This two-step process represents an overall acylation or carbonylation of an olefin.
B. T. Lee, T. O. Schrader, B. Martin-Matute, C. R. Kauffman, P. Zhang, M. L. Snapper, Tetrahedron, 2004, 60, 7391-7396.
The combination of Mo and cationic Au catalysts dramatically accelerated the rearrangement of diverse propargyl alcohols to yield α,β-unsaturated compounds under mild conditions, and high product yields. A practical application to the highly challenging primary propargyl alcohols and the N-alkynyl amides is achieved.
M. Egi, Y. Yamaguchi, N. Fujiwara, S. Akai, Org. Lett., 2008, 10, 1867-1870.
The use of cationic silver (AgSbF4) as a catalyst for intra- and intermolecular alkyne-carbonyl coupling is described. Intermolecular coupling proceeds stereoselectively to afford trisubstituted enones.
J. U. Rhee, M. J. Krische, Org. Lett., 2005, 7, 2493-2495.
A novel, convenient and stereoselective synthesis of trisubstituted E-alkenones has been achieved by InCl3-mediated chemoselective reduction of Baylis-Hillman adducts with NaBH4 as reductant.
B. Das, J. Banerjee, N. Chowdhury, A. Majhi, H. Holla, Synlett, 2006, 1879-1882.
Various α,β-unsaturated ketones were stereoselectively synthesized in high yields by a condensation of alkenyl trichloroacetates with aldehydes using the mild base dibutyltin dimethoxide as a catalyst in the presence of methanol.
A. Yanagisawa, R. Goudu, T. Arai, Org. Lett., 2004, 6, 4281-4283.
A proazaphosphatrane is a very efficient catalyst for Mukaiyama aldol reactions of aldehydes with trimethylsilyl enolates in THF solvent. The reaction conditions are mild and operationally simple, and a variety of aryl functional groups, such as nitro, amino, ester, chloro, trifluorometh yl, bromo, iodo, cyano, and fluoro groups, are tolerated.
V. R. Chintareddy, K. Wadhwa, J. G. Verkade, J. Org. Chem., 2009, 74, 8118-8132.
Palladium-catalyzed oxygenation of allyl arenes or alkenes produce (E)-alkenyl aldehydes with high yields. Allylic C-H bond cleavages occur under mild conditions during this process. Mechanistic studies show that oxygen source is water.
H. Chen, H. Jiang, C. Cai, J. Dong, W. Fu, Org. Lett., 2011, 13, 992-994.
A synthesis of β,γ-unsaturated α-keto esters directly from aldehydes and pyruvates is promoted by BF3•Et2O in the presence of Ac2O or by Ti(OEt)4 under mild conditions. Various aldehydes afford the desired products in good yield. Moreover, aliphatic aldehydes and Isatin were also employed to give the γ-alkyl β,γ-unsaturated α-keto esters in moderate yield with use of the Ti(OEt)4 system.
J. K. Mansaray, J. Sun, S. Huang, W. Yao, Synlett, 2019, 30, 809-812.
A palladium-catalyzed oxidative dehydrogenation enables an efficient synthesis of 1,4-enediones from saturated ketones in the presence of molecular oxygen as the sole oxidant. This atom- and step-economic process offers broad substrate scope, good functional group tolerance, and complete E-stereoselectivity.
B.-Y. Zhao, X.-L. Zhang, R.-L. Guo, M.-Y. Wang, Y.-R. Gao, Y.-Q. Wang, Org. Lett., 2021, 23, 1216-1221.
A palladium-catalyzed allylic C-H oxidative allylation of sulfoxonium ylides provides conjugated dienones in good yields. This conversion offers mild reaction conditions, wide substrate scope, and excellent regioselectivity.
C. Li, M. Li, W. Zhong, Y. Jin, Y. Jin, J. Li, W. Wu, H. Jiang, Org. Lett., 2019, 21, 872-875.
A Rh(I)-catalyzed propargyl Claisen rearrangement followed by stereoselective hydrogen transfer enables the synthesis of functionalized (E,Z) dienals from propargyl vinyl ethers. Z-Stereochemistry of the first double bond suggests the involvement of a six-membered cyclic intermediate whereas the E-stereochemistry of the second double bond stems from the subsequent protodemetalation step giving an (E,Z)-dienal.
D. V. Vidhani, M. E. Krafft, I. V. Alabugin, Org. Lett., 2013, 15, 4462-4465.
A domino reaction of enolizable carbonyl compounds with Me3SiCF2Br provides α-fluoroenones and α-fluoroenals via formation of difluorocarbene and silyl enol ether, difluorocyclopropanation, desilylation, ring-opening, and defluorination. Me3SiCF2Br acts as not only the difluorocarbene source but also the TMS transfer agent as well as internal bromide and fluoride anion catalyst. Only a catalytic amount of n-Bu4NBr as initiator is needed.
X. Song, J. Chang, D. Zhu, J. Li, C. Xu, Q. Liu, M. Wang, Org. Lett., 2015, 17, 1712-1715.
Titanium(IV) halides mediate a highly stereoselective vicinal difuctionalization of α,β-unsaturated ketones to provide multifunctionalized trisubstituted alkenes in very good yields and high Z:E stereoselectivity. The reaction can be performed at room temperature in a convenient vial under air.
G. Li, J. Gao, H.-X. Wei, M. Enright, Org. Lett., 2000, 2, 617-620.
A copper-amine catalyst system enables a general and facile synthetic method for β-fluoroenones from silyl enol ethers or ketones via tandem process of difluoroalkylation-hydrolysis-dehydrofluorination. This reaction offers high yields, excellent Z/E ratios, a low-cost catalyst, and a broad substrate scope.
Y. Li, J. Liu, S. Zhao, Y. Du, M. Guo, W. Zhao, X. Tang, G. Wang, Org. Lett., 2018, 20, 917-920.
Pd(DMSO)2(TFA)2 as a catalyst enables a direct dehydrogenation of cyclohexanones and other cyclic ketones to the corresponding enones, using O2 as the oxidant. α,β-Unsaturated carbonyl compounds are versatile intermediates in the synthesis of pharmaceuticals and biologically active compounds. The substrate scope includes heterocyclic ketones and several natural-product precursors.
T. Diao, S. S. Stahl, J. Am. Chem. Soc., 2011, 133, 14566-14569.
A practical and environmentally friendly method for the oxidative rearrangement of five- and six-membered cyclic tertiary allylic alcohols to α,β-unsaturated β-disubstituted ketones by IBX in DMSO is described. Several conventional protecting groups (e.g., Ac, MOM, and TBDPS) are tolerated.
M. Shibuya, S. Ito, M. Takahashi, Y. Iwabuchi, Org. Lett., 2004, 6, 4303-4306.
trans-2-Aryl-3-nitro-cyclopropane-1,1-dicarboxylates undergo ring-opening rearrangement and the Nef reaction in the presence of BF3·OEt2 to give aroylmethylidene malonates. The products are potential precursors for heterocycles, such as imidazoles, quinoxalines, and benzo[1,4]thiazines.
T. Selvi, K. Srinivasan, J. Org. Chem., 2014, 79, 3653-3658.
1,3-dicarbonyl compounds and methyl ketones or terminal aryl alkenes as simple and readily available starting materials can be efficiently converted to unsymmetrical 1,4-enediones under mild reaction conditions using a focusing domino strategy. The reaction allows an operationally simple, straightforward synthesis of various unsymmetrical 1,4-enediones.
M. Gao, Y. Yang, Y.-D. Wu, C. Deng, L.-P. Cao, X.-G. Meng, A.-X. Wu, Org. Lett., 2010, 12, 1856-1859.