Electron deficient enol silyl ethers

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

Silyl enol ethers are inherently less reactive than silyl ketene acetals but are competent partners in this reaction with increased reaction times. Electron- deficient aldehydes provide the highest yields while 4-methoxybenzaldehyde proceeds in only 10% yield after 65 h (Eq. 36). 

Several examples of Bi(0Tf)34H20-catalyzed Mannich-type reactions of various A-benzyloxycarbonylamino sulfones 1 with silyl enol ethers are summarized in Table 5. A-Benzyloxycarbonylamino sulfones 1 derived from differently substituted benzaldehydes were reacted with trimethyl(l-phenylvinyloxy)silane in dichloromethane at room temperature. The corresponding (3-amino ketones 24 were smoothly obtained (Table 5, entries 1-6). The reaction was efficient using electron-deficient benzaldehyde-derived sulfones, and the corresponding (3-amino ketones 24... 

Palladium-catalyzed three-component coupling of dimethylsilacyclobutane, carbon monoxide, and aromatic iodides also yields cyclic silyl enol ethers via a ring/expansion/-insertion process <1996CC1207>. Electron-rich and electron-deficient aromatic iodides are suitable substrates, giving rise to the corresponding cyclic silyl enol ethers in excellent yields (Scheme 50). 

Substrates containing an electron-rich double bond, such as enol ethers and enol acetates, are easily oxidized by means of PET to electron-deficient aromatic compounds, such as dicyanoanthracene (DCA) or dicyanonaphthalene (DCN), which act as photosensitizers. Cyclization reactions of the initially formed silyloxy radical cation in cyclic silyl enol ethers tethered to an olefinic or an electron-rich aromatic ring, can produce bicyclic and tricyclic ketones with definite stereochemistry (Scheme 9.14) [20, 21]. 

For both types of substituent, the effects are more marked on the more distant ((3) proton. If these shifts reflect the true electron distribution, we can deduce that nucleophiles will attack the electron-deficient site in the nitroalkene, while electrophiles will be attacked by the electron-rich sites in silyl enol ethers and enamines. These are all important reagents and do indeed react as we predict, as you will see in later chapters. Look at the difference—there are nearly 3 p.p.m. between the nitro compound and the enamine ... 

Coupling of ketones with electron-deficient alkenes via a methylene group (cf. II, 315-316). This modified Giese reaction involves cyclopropanation of the silyl enol ether of a ketone, mcrcuration, and finally demercuration and coupling with an alkcnc via a radical chain reaction. 

N-Acyliminium ion pools react with various carbon nucleophiles as summarized in Scheme 5.16. For example, allylsilanes, silyl enol ethers, Grignard reagents, and 1,3-dicarbonyl compounds serve as good nucleophiles. Aromatic and heteroaromatic compounds also react as nucleophiles with N-acyliminium ion pools to give Friedel-Crafts-type alkylation products.N-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4 -F 2] cycloaddition with alkenes and alkynes. Usually these reactions take place very quickly, and therefore N-acyliminium ion pools serve as effective reagents for flash chemistry. 

Mizuno, Pac, and co-workers reported photo-Michael reactions via the 2n+2n photocycloaddition-hydrolysis sequences of silyl enol ethers with electron-deficient alkenes such as acrylonitrile, methyl acrylate, and 1-cyanonaphthalene. - Similarly, regioselective 2jr+27l-photocycloaddition of 1-trimethylsiloxynaphthalene with... 

Shibasaki and co-workers used a ring-closing metathesis approach to prepare a number of five-, six-, and seven-membered rings from electron-deficient olefins. Treatment of acyclic enol ether 18 with 7 mol % of 3 in refluxing benzene provided the corresponding cyclic enol ether 19 in 94% yield. Deprotection of the silyl ether 19 (not shown) resulted in the corresponding cyclic ketone, a valuable synthetic intermediate in natural products synthesis and a number of industrial processes. The authors reported additional examples of the synthesis of five-membered ring carbocycles as part of this study. 

The proposed catalytic cycle for the above-described conjugate reduction is outlined in Scheme 17. Initial coordination of the nucleophilic Pd(0)-phosphine complex to the electron-deficient olefin to form complex I is a reversible process that occurs rapidly at room temperature. Oxidative addition of the sihcon hydride moiety to complex I would result in the hydrido olefin complex II. Migratory insertion of the hydride ligand into the electrophilic /S-carbon of the coordinated olefin can result in the palladium enolate intermediate in. Reductive elimination of the silicon moiety and the enolate completes the catalytic cycle and forms the silyl enol ether IV. The latter is prone to acid-catalyzed hydrolysis to produce the saturated ketone. "" ... 

As a direct route for the constructing carbon-carbon bonds, catalytic asymmetric Michael additions with various carbon-based nucleophiles including malonic esters, cyanide, electron-deficient nitrile derivatives, a-nitroesters, nitroalkanes, Horner-Wadsworth-Emmons reagent, indoles, and silyl enol ethers have attracted considerable attention. 

Photoinduced reactions of cyclic a-diketones with different alkenes takes place via [2 + 2], [4 + 2] or [4 + 4] photocycloaddition pathways. Photoaddition of electron deficient silyl ketene acetals to 2-, 3- and 4-acetylpyridine generates oxetanes as major products. The reaction is favoured in non polar solvents. The photoreaction between silyl enol ethers and henzil affords [2 + 2] cycloaddition products, while in the case of 9,10-phenanthrenequinone [4 + 2] cycloacidition predominates. Photocycloaddition of p-henzoquinones to hicyclopropylidene affords spirooxetanes (21) as the primacy products further irradiation leads to rearranged spiro[4.5]deca-6,9-diene-2,8-diones. With 9,10-anthraqui-none, in addition to the spirooxetane, a spiro[indan-l,l -phthalan]-3 -one is also obtained. ... 

In the early 1960s, Brannock et al. reported a thermal [2+2] cycloaddition of enamines. Enamines react with a variety of electron-deficient alkenes such as acrylates, nitro-olefines, acetonitriles, vinylsulfones, fumarates, and malei-mides to give aminocyclobutanes [4]. The reaction generally does not require the assistance of an acid catalyst. Narasaka et al. exploited asymmetric thermal [2+2] cycloaddition of vinyl and aUenyl sulfides with electron-deficient alkenes catalyzed by Lewis acid [5]. Yamazaki et al. have reported that a stoichiometric amount of Lewis acid activates [2+2] cycloaddition of vinylselenides with highly electron-deficient olefins [6]. These reactions proceed via a stepwise annulation to give mercapto- and seleno-cyclobutanes, respectively. However, cyclobutane formation from silyl enol ethers, which are one of the most easily prepared ketone... 

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