Yield is based on conversion to the dienone. Table 7. However, less reactive reagents such as lithium dimethylcuprate give poor yields whilst more hindered enol phosphates are unreactive <76TL4405>. However, two α carbon atoms may form enols of a ketone. Asymmetric hydrogenation of α-(acyloxy) acrylates, Although high hydrogen pressure is required, BINAP and its analogous ligands have shown superior results in the Ru-catalyzed hydrogenation of four- and five-membered cyclic lactones or carbonates bearing an exocyclic methylene group.233 An (S)-SEGPHOS–Ru catalyst provides 93.8% ee in the hydrogenation of a diketene with high turnover numbers (Equation (38)).236 With an (S)-BINAP–Ru catalyst, 94% ee is obtained in the hydrogenation of 4-methylene-γ-butyrolactone (Equation (39)). The primary work with enol acetates108 displayed solely the prototropic ene reaction generating the corresponding enones. The amount of enol in equilibrium with the carbonyl compound depends on structural factors that affect the stability of both the carbonyl compound and the enol. The reaction proceeds in most polar solvents, for example, DMF, DMSO, HMPA and N,N′-dimethyl-propyleneurea (DMPU), which not only solubilise LiCl but also act as ligands for the intermediate complexes in the catalytic cycle <86JA3033>. We use cookies to help provide and enhance our service and tailor content and ads. Although perhaps not widely applicable, these processes could find useful application in some instances. 540420 [(1E)-1 … = 54–55 °C) while perfluoroethenol (perfluoroacetaldehyde enol) (25) is not known. Finally, electrochemical acetoxylation of enol acetates occurs in moderate yield.118. Reactions C–C bond formation Subsequent hydrolysis of the enol silane during acid-base work-up affords the Mannich base (59). These reactions are highly stereospecific and a range of organoaluminum compounds can be used with alkenyl- and alkynylaluminum ligands showing greater migratory aptitude than alkyl groups. Me–PennPhos is found to be efficient for the Rh-catalyzed hydrogenation of five- or six-membered ring cyclic enol acetates (Equation (37)).66a Hydrogenation of acyclic enol acetates is also possible. Table 9. Greater selectivity can be achieved through the use of NiCl2(dppp) or related chelating phosphines. In the corresponding reactions of TBDMS enol silanes (60), Akiba and coworkers have shown that the more stable TBDMS group is able to survive the work-up, affording Mannich bases as their TBDMS enol silane derivatives (62; Scheme 12).56 Interestingly, acyclic TBDMS enol silanes react with migration of the position of the enol silane double bond (Table 7, entries 1–4). For further examples, see the mini-review by Holy.35, Table 8. A wide range of 2-(acyloxy)acrylates has been hydrogenated with an Et–DuPhos–Rh catalyst with excellent ee.229 High selectivities are also obtained in the hydrogenation of the E/Z-isomeric mixtures of β-substituted substrates. This reaction is completely supressed in acetonitrile (86BCJ3625). Treatment of enol acetates with LTA in acetic acid affords α-acetoxy ketones.112,113 For example the tetracyclic substrate (82) is converted to the α-acetoxy derivative (83) in 95% yield and provides a step in the total synthesis of cycloneosamandione.114 Vinyl ethers react similarly, suggesting that alkyl enol ethers should follow suit. Alternatively, enolate salts react with silyl electrophiles. Most commonly, fluorinated enols are prepared by the acid hydrolysis of benzyl enol ethers. Enzymes, Enzyme Mechanisms, Proteins, and Aspects of NO Chemistry. One example involves the racemization of mandelic acid catalyzed by the enzyme mandelate racemase (Equation (3), ).15 The enol of mandelic acid is believed to be an intermediate in the enzymatic reaction. Enol triflates couple with the allyl or benzyl Grignard reagent in the presence of Li2MnCl4 as a catalyst to give coupling products in high yields (equation 59). This reaction often involves a nucleophilic solvent to give an addition product. The enol tautomerizes rapidly and only the corresponding ketone is obtained. FeCl3, SnCl4 or BF3-OEt2) gives moderate yields of α-acetoxy and α-hydroxy ketones.117 A similar transformation is possible for some large ring enols. (Scheme B.2.4). Add to Cart. Enol ethers have oxonium ion character. However, in contrast to many highly enantioselective examples of the asymmetric hydrogenation of enamides, only a few successful results have been reported for the hydrogenation of enol esters. Various vinyl ethers may also be converted to substituted alkenes on treatment with Grignard reagents in the presence of nickel catalysts. We recall that conjugation of two carbon-carbon double bonds of butadiene results in resonance stabilization of approximately 15 kJ mole− 1. The discussion outlined above (Section 2.3.2.1.3.ii) for the interaction of singlet oxygen with silyl enol ethers is equally relevant here. β-Diketones provide a more dramatic demonstration of the effect of double bond stability on the concentration of the enol form. We recall that a ketone is more stable than an aldehyde because two alkyl groups donate electron density to the carbonyl carbon atom of a ketone versus only one for an aldehyde. Kinetic studies of enolpyruvate indicate that it undergoes buffer-catalyzed ketonization.8,9 These solution studies also provide a partial explanation for the energy released by the hydrolysis of phosphoenolpyruvate (Equation (4)), an intermediate in glycolysis.4 The energy of phosphoenolpyruvate is derived from a two-step process: the first step involves hydrolysis of phosphoenolpyruvate and the second ketonization of enolpyruvate. Furthermore, the newly formed alkene may be introduced in a regioselective fashion via trapping of the regioselectively formed enolate.67, The success of the reaction is dependent upon the presence of Pd(Ph3)4, since the addition fails in the absence of Pd or in the presence of either nickel or Pd(acac)2.66, Peter Goekjian, ... Claire Coiffier, in C-Furanosides, 2018. Furthermore, the use of a basic solvent (ether, dioxane or THF) is essential. The carbon-carbon double bond of the enol of cyclohexanone is more highly substituted than the carbon-carbon double bond of the enol of acetone. Similarly, treatment of the (1,2-dialkoxyethylene) iron complexes (17) with cuprates, Grignard reagents or enolates affords moderate yields of either the cis or trans alkenes (Scheme 21) <84JA7264>. Similarly, they undergo inverse demand Diels-Alder reactions. The enol with the more substituted double bond predominates because alkyl groups stabilize double bonds. Palladium catalysis is also required for the displacement of enol phosphates with trialkylmanganates, R3MnM (M = Li, MgBr), prepared in situ from Li2MnCl4 and the organometallic species <87CL2203>. In general, pyran substrates are less reactive requiring higher catalyst loadings, longer reaction times and give more modest yields (50–60%), failing completely with Grignard reagents possessing β-hydrogen atoms <92JCS(P1)3431>. Here however the ene process seems to be less inevitable when allylic protons are available and the product distribution may be effectively controlled by manipulation of solvent and temperature combinations.110 Best results are nonetheless achieved where the competitive processes are restricted.111 Thus enol ether (79) produces hydroxylated dimethoxy acetal (80) via direct incorporation of methanol or through reduction of the 1,2-dioxetane (81). Numerous other examples are available.100 Where dienol acetates are utilized, the product is derived from epoxidation of the more nucleophilic, remote unsaturation.101 Both thermodynamic and kinetic enol acetates may be prepared102 (although with less precision than the silyl equivalent), allowing a useful degree of regiocontrol. Reagents derived from organolithiums are superior to those from the corresponding Grignard reagent whilst higher alkyl reagents tend to give side-products from reduction and vinyl coupling. Akin to enamines, enol ethers are electron-rich alkenes by virtue of the electron-donation from the heteroatom via pi-bonding. Enol Ethers. Table 2. Grignard reagents possessing β-hydrogen atoms are considerably less reactive, giving product mixtures containing reduction and isomerised by-products. Keto–enol tautomerization represents a classical area of study in organic chemistry.1 The enolization of carbonyl compounds in the presence of acid or base has been studied extensively and the mechanisms and the supporting evidence are reviewed elsewhere.1–3 The stability of the transition state in either acid- or base-catalyzed enolization or ketonization is influenced by a number of factors resulting in an effect on the rate of enolization and ketonization.2 Among these factors is stereoelectronic control. The most reactive pentachloropyridinium reagent (5b) causes fluorination of styrene, substituted styrenes such as 25, 1,1-disubstituted ethylenes, and trisubstituted ethylenes. Mannich Reactions of Enol Silanes Using N,N-Dimethyl(methylene)iminium Salts. Unlike the corresponding nickel-catalysed Grignard displacements, a variety of other vinyl leaving groups are stable, notably vinyl sulphides, and this can lead to the stereocontrolled synthesis of tri- and tetrasubstituted alkenes. Enol alkyl ethers, enol silyl ethers, vinyl esters, and enamines undergo reactions with N-fluoropyridinium salts to give α-fluoroketones, as illustrated for the selected substrates 21–24. ).8,9 The compound has been generated by the action of acid phosphatase on phosphoenolpyruvate in acidic solutions and by the silylation of deprotonated pyruvic acid.8,9 The latter compound, bis-TMS-enolpyruvate, is stable for several weeks at −20 °C. Although vinyl Grignard reagents are not suitable, a range of other alkyl and aryl Grignards are effective and provided the reaction is quenched efficiently almost complete stereoselectivity can be observed <92JCS(P1)3419>. Reaction of enol acetates with hexamethyldisilyl peroxide in the presence of a Lewis acid (e.g. An intramolecular hydrogen bond can stabilize a structure by approximately 20 kJ mole− 1. Copyright © 2020 Elsevier B.V. or its licensors or contributors. Only one α carbon atom exists in an aldehyde. With higher alkyl Grignard reagents, competing reduction through β-hydrogen elimination can be suppressed through the use of the ferrocenyl ligand (dppf). Table 5. The presence of β-hydrogen atoms in the Grignard component can be problematical although the use of bidentate phosphine ligands, for example, NiCl2(dppp), can circumvent this difficulty <83TL5137>. Patrick G. Steel, in Comprehensive Organic Functional Group Transformations, 1995. A similar stabilization is reasonable for a carbon-carbon double bond in conjugation with a carbonyl group. Synthesis. Both alkyl enol ethers <84JOC4894>, and silyl enol ethers <80TL3915> undergo the reaction with aryl and alkyl Grignard reagents. In the presence of ≤2 mol% of tetrakis(triphenylphosphine)palladium and at least one equivalent of LiCl, a variety of organostannanes (alkyl, vinyl, acetylenic and aryl) couple efficiently <93S735>. In general, the relative stabilities of the double bonds of the two enols account for the amount of each enol formed. Edward F. Kleinman, in Comprehensive Organic Synthesis, 1991. The ketal is lost during work-up; yield is based on conversion to the methiodide salt. Molecular Formula. Enol phosphates may be simply converted to the corresponding alkenes on treatment with reactive cuprates such as lithium dibutylcuprate.