Enamine enol ethers

These compounds typically react with electrophiles on carbon and in this respect they resemble enamines, enol ethers and enol thioethers. For example, both pyrrole and 1-pyrrolidinocyclohexene can be C-acetylated (Scheme 4). 

The enamines, enol ethers and enol acetates of A -3-keto steroids provide important substrates for fluorination with FCIO3. Reaction of such A -enol ethers and acetates (6) with perchloryl fluoride results in 6a- and 6jff-fluoro-A -3-ketones (7) and (8), the latter representing the more abundant isomer. Tetrahydrofuran or dioxane-water mixtures appear to be particu-... 

Fluorination of an enamine, enol ether, or enol acetate with CF3OF gave 60-70% yields of fluoroketone (708). Bromination of an endiamine gave the bis-imonium salt (647). 

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

Very recently a number of intermolecular a-amidoalkylation reactions related to the formation of C-C bonds with simple diastereoselection have been reported only activated 7t-nucle-ophiles, such as allylsilanes, enamines, enol ethers, etc. are used83 - 88. 

Cyclobutanes can also be formed by nonconcerted processes involving zwitter-ionic intermediates. The combination of an electron-rich alkene (enamine, enol ether) and an electrophilic one (nitro- or polycyanoalkene) is required for such processes. 

In addition to the role of substituents in determining regioselectivity, several other structural features affect the reactivity of dipolarophiles. Strain increases reactivity. Norbomene, for example, is consistently more reactive than cyclohexene in 1,3-dipolar cycloadditions. Conjugated functional groups also usually increase reactivity. This increased reactivity has most often been demonstrated with electron-attracting substituents, but for some 1,3-dipoles, enamines, enol ethers, and other alkenes with donor substituents are also quite reactive. Some reactivity data for a series of alkenes with a few 1,3-dipoles are given in Table 6.3. Scheme 6.5 gives some examples of 1,3-dipolar cycloaddition reactions. 

In origin, the Mannich reaction is a three-component reaction between an eno-lizable CH-acidic carbonyl compound, an amine, and an aldehyde producing / -aminocarbonyl compounds. Such direct Mannich reactions can encompass severe selectivity problems since both the aldehyde and the CH-acidic substrate can often act as either nucleophile or electrophile. Aldol addition and condensation reactions can be additional competing processes. Therefore preformed electrophiles (imines, iminium salts, hydrazones) or nucleophiles (enolates, enamines, enol ethers), or both, are often used, which allows the assignment of a specific role to each car-... 

However, in recent years, it has become apparent that several photoinduced oxidation reactions do not involve singlet oxygen as the reactive intermediate, and, consequently, the reaction products cannot be accounted for the mechanisms shortly reported above. Moreover, since the first report on the photochemical stereospecific synthesis of the most fascinating peroxide derivatives, i.e., 1,2-dioxetanes [32], it clearly appeared, with a few notable exceptions [33,38], that only electron-rich olefins, such as enamines, enol ethers, and thio-substituted... 

One of the classic approaches toward cyclobutanes and cyclobutenes, [2+2] cycloaddition between electron-rich and electron-poor alkenes or alkynes, is mirrored by the in situ reaction of [W(CO)5] adducts of electron-deficient phosphaalkenes with enamines, enol ethers, ynamines, and ethoxyacetylene to yield the corresponding phosphetanes and 1,2-dihydrophosphetes.21 Prior... 

Whereas the allyl anion, with a plane of symmetry through the central atom, has a node at that atom in j/ j, amides, esters, enamines, enol ethers and enolate ions do not have a node precisely on the central atom. Taking planar A V-dimethylviny-lamine and the enolate of acetaldehyde as examples, simple Hiickel calculations give the n orbitals in Fig. 2.15, which includes the allyl anion for comparison. 

For additions of enamines, enol ethers and isonitriles see text. 

Enamines, enol ethers and related compounds again encompass one-site nucleophiles and two-site dipolarophiles. Where the adducts are acyclic or where a coelectrophile is involved these appear to be examples of equation (1). In equations (217)-(219), the paths to the major products seem straightforward. While a competing... 

Enolate Enamine Enol ether Vinyl halide... 

Enamines. enol ethers, or vinyl sulfides with E geometry can be obtained by thermal Cope rearrangement of 3-hetero-substituted substrates, e.g., 48, 50. and 52811. 

Aromatization also occurs easily if alcohol, thiol, or amine can be eliminated from a trans-arrangement of substituents. The cycloaddition step is especially fast if ketene aminals, enamines, enol ethers, enol esters, or trimethylsilyloxyalkenes are used as 27t-compounds. The reaction enthalpy A/f for the eycloaddition of 1,3-eyelopentadiene or 1-hexene to dimethyl tetrazinedicarboxylate is in the range of 60-70 kcal mol <93ZORi7i9>. 

Aromatic and aliphatic acyl isocyanates participate in a similar range of [4 + 2] cycloadditions although [2 + 2] and simple addition reactions often are observed. The acyl isocyanate substituents may determine or alter the observed course of the reaction, and the substituent effects have been detailed in extensive reviews.7,71 Observed [4 + 2] cycloadditions of acyl isocyanates with selected olefins, p-quinones, allenes, the carbon-carbon double bond of ketenes, electron-rich acetylenes, imines, dianils, ethy-lenediimines, enamines, enol ethers, ketene acetals, carbodiimides, azirines, and vinyl sulfides have been described.7 0 The reaction of aromatic acyl isocyanates with carbodiimides is not a simple, direct [4 + 2] cycloaddition but proceeds by a kinetic [2 + 2] cycloaddition followed by a subsequent rearrangement to provide the observed [4 + 2] cycloadduct [Eq. (40)].97... 

First, we will consider oxygenation of chemical substrates, including alkenes, enamines, enol ethers, and ketenes. Subsequently we shall take up the oxygenation of biological substrates. 

Among the reactions of the 1,2,4-triazines, the hetero-DlELS-ALDER reactions with electron-rich alkenes and alkynes are of special importance in preparative chemistry [168]. The heterocyclic ring reacts with enamines, enol ethers and ketene acetals as an electron-deficient 2,3-diazadiene across the ring positions C-3 and C-6 ... 

The regiospecificity of addition of substituted alkenes to azides is not as absolute as the preceeding examples with enamines, enol ethers, and acceptor-substituted alkenes may imply in all those cases the reverse addition product was not detected. This does not mean that it cannot be formed. Ouali et al. (1980) found cases in which both isomers were indeed obtained. Methyl acrylates with an acceptor substituent at... 

Because of their predictable behavior and reactivity, thioacyl isocyanates comprise the bulk of this work, and extensive studies of their [4 -I- 2] reactions with olefins, enamines, enol ethers, thioacyl isocyanates, imines, carbodiimides, isocyanates, azirines, /3-enaminoke-tones, dianils, azines, hydrazones, imidazoline-4,5-diones, aryl cyanates, disubstituted cyanamides, aldehydes, ketones, ketenes, alkyl or aryl iminodithiocarbonates, and the carbon-carbon double bond of ketenimines have been detailed. In an extensive comparative study of the [4 + 2] cycloaddition reactions of thioacyl isocyanates, the heterocu-mulenes bearing strong electron-withdrawing substituents were found to be more stable and less prone to participate in cycloaddition reactions. Representative examples are summarized in Scheme 9-IV. 

Like enamines, enol ethers are sufficiently electron rich to undergo flZfl-Diels-Alder chemistry with high efficiency under mild conditions. For example, 2,3-dihydrofuran 90 reacts with triazines 89 to give pyridines with pendant protected alcohols 91 (09T975) (Scheme 31-A) or pyridines bearing annulated lactones 92 (04T8893) (Scheme 31-B) as the ultimate products, depending on the substitution pattern of the 1,2,4-triazine 89. 

Synthesis of enamines, enol ethers, and related compounds by cross-coupling reactions, particularly, synthesis of heterocycles including natural products 05CC973. 

Other Reactions Oxallyls, formed from a,a -dibromoketones and Fe2(CO)9, react with alkenes, enamines, enol ethers, amides, or dienes to give a variety of [3 + 2] and [3 + 4] cycloaddition products (Eq. 14.71). This provides a very short synthesis of the tropane skeleton from acetone and pyrrole (Eq. 14.72). As shown in Eq. 14.71, an oxallyl resembles trimeth-ylenemethane (5.22) except that one =CH2 of 5.22 is replaced by =0. 

Enamines, Enol Ethers, and Eiad Acetates.— Enamines and imines derived from cycloheptanone and cyclo-octanone have been used in a variety of alkyla-tions. Enol acetates of these ketones have been converted into 2-(l-acetoxy-ethyl)cycloalkanol acetates by treatment with di-isobutylaluminium hydride followed by acetic anhydride. ... 

Numerous carbon nucleophiles participate in the Nicholas reaction the most popular are electron rich aromatics, enamines, enol ethers, ketene acetals, alkenes, allylsilanes, allylstannanes, and organoaluminum compounds. Upon completion of the substitution reaction, the cobalt complex can be oxidatively removed with E, Fe(III), or Ce(IV). Additional chemistry based on cobalt-complexed alkynes, like the Pauson-Khand reaction, can also be performed to further increase molecular complexity. 

Enamine Enol Ether Enol Triflate Epoxide... 

Acylation of Enol Ethers, Ketene Acetals, and Enamines. Enol ethers, ketene acetals (eq 24), and enamines (eq 25) react with PhCOCI to provide the corresponding p-acylated products (eq 24). The acylation of enamines has been extensively studied (eq 25) the resulting P-acyl enamine is generally hydrolyzed to give p-diketones (eq 25). 

---