Enophiles

Fluoroalkyl acetylenes are powerful enophiles and Diels-Alder dienophiles but also can give good yields of cyclobutenes in their cycloadditions [115,116,117] (equations 48 and 49)... 

Several highly enantioselective Diels-Alder reactions are known for which the di-enophile does not fit any of the above classes. Corey and coworkers applied the chiral aluminum reagent 36 with a C2-symmetric stilbenediamine moiety (videsu-pra) to the Diels-Alder reaction of maleimides as dienophiles [54] (Scheme 1.68). In most asymmetric Diels-Alder reactions the reactants are usually relatively simple dienes such as cyclopentadiene or monosubstituted butadienes, and unsym-... 

The ene reaction as a reaction principle has been first recognized and systematically investigated by Alder It is a thermal addition reaction of a double bond species 2—the enophile—and an alkene 1—the ene—that has at least one allylic hydrogen. The intramolecular variant is of greater synthetic importance than is the intermolecular reaction. 

The overall reaction includes allylic transposition of a double bond, migration of the allylic hydrogen and formation of a bond between ene and enophile. Experimental findings suggest a concerted mechanism. Alternatively a diradical species 4 might be formed as intermediate however such a species should also give rise to formation of a cyclobutane derivative 5 as a side-product. If such a by-product is not observed, one might exclude the diradical pathway ... 

A primary allylic hydrogen at the ene 1 is especially reactive a secondary hydrogen migrates less facile, and a tertiary one is even less reactive. The enophile unit should be of an electron-poor nature it can consist of a carbon-carbon double or triple bond, a carbonyl group or an azo group. Mixtures of regioisomeric products may be obtained with substituted enophiles. The acrylic ester 6 reacts with... 

Interestingly, in the inverse-electron-demand Diels-Alder reactions of oxepin with various enophiles such as cyclopentadienones and tetrazines the oxepin form, rather than the benzene oxide, undergoes the cycloaddition.234 236 Usually, the central C-C double bond acts as dienophile. Oxepin reacts with 2,5-dimethyl-3,4-diphenylcyclopenta-2,4-dienone to give the cycloadduct 6 across the 4,5-C-C double bond of the heterocycle.234 The adduct resists thermal carbon monoxide elimination but undergoes cycloreversion to oxepin and the cyclopenta-dienone.234... 

Phthalocyanines with side groups which can undergo Diels-Alder reactions can be synthesized as precursors for ladder polymers (see pp772, 773).344-345 For these kinds of compounds an intrinsic conductivity is predicted.346 Both dienophilic and enophilic phthalocyanines have been prepared. The possibility to undergo a Diels-Alder reaction was tested with fumaronitrile and 2,3-dimethylbutadiene.345 Via a Diels-Alder reaction, a connection between a phthalocyanine and [60]fullercne was also achieved.336... 

Lewis acid-mediated asymmetric Diels-Alder reactions between 2H-azirines 59, bearing chiral auxiliaries, with enophiles such as 60 afforded mixtures of bicyclic aziridine-2-carboxylates 61 (Scheme 3.20) [68]. 8-Phenylmenthol appeared to be the auxiliary of choice in this reaction in terms of yield and diastereoselectivity. 

Enhancement of dienophilic and enophilic reactivity of the giyoxyiic acid by bismuth (III) triflate in the presence of water [28]... 

Racemic pyrone sulfoxide 52 undergoes a diastereoselective inverse-electron-demand 2 -f 4-cycloaddition with 1,1-dimethoxyethylene to afford adduct 53 in > 95% yield (equation 49) this is the first example of an asymmetric Diels-Alder cycloaddition using a sulfinyldiene as an electron-deficient enophile . 

Ene and Carbonyl-Ene Reactions. Certain double bonds undergo electrophilic addition reactions with alkenes in which an allylic hydrogen is transferred to the reactant. This process is called the ene reaction and the electrophile is known as an enophile A When a carbonyl group serves as the enophile, the reaction is called a carbonyl-ene reaction and leads to [3,-y-unsalurated alcohols. The reaction is also called the Prins reaction. 

The concerted mechanism shown above is allowed by the Woodward-Hoffmann rules. The TS involves the tt electrons of the alkene and enophile and the cr electrons of the allylic C-H bond. The reaction is classified as a [tt2 + tt2 + cr2] and either an FMO or basis set orbital array indicates an allowed concerted process. 

Because the enophiles are normally the electrophilic reagent, their reactivity increases with addition of EWG substituents. Ene reactions between unsubstituted alkenes have high-energy barriers, but compounds such as acrylate or propynoate esters... 

Scheme 10.2 gives some examples of ene and carbonyl-ene reactions. Entries 1 and 2 are thermal ene reactions. Entries 3 to 7 are intermolecular ene and carbonyl-ene reactions involving Lewis acid catalysts. Entry 3 is interesting in that it exhibits a significant preference for the terminal double bond. Entry 4 demonstrates the reactivity of methyl propynoate as an enophile. Nonterminal alkenes tend to give cyclobutenes with this reagent combination. The reaction in Entry 5 uses an acetal as the reactant, with an oxonium ion being the electrophilic intermediate. 

The reaction of dienes bearing an A-dienyl lactam moiety with activated olefins was examined by Smith.94 The lactams were excellent enophiles and provided exclusively the ortho regioisomer with good selectivity for the endo (Z) product (Eq. 12.33). 

Ene reactions tended to occur as alternative reaction pathways to [2 + 4] cycloaddition, especially when sterically bulky silenes had substituents on the sp2-hybridized carbon atom and dimethylbutadiene served as the diene component. In the ene reactions studied the silene acted as the enophile as often as it acted as the ene. 

Even the 2,3-dimethyl-l,3-butadiene reacts as an enophile, not as a diene1428-29 ... 

For the components with a conjugated diene system, derivatization with MTAD is useful to determine the unsaturated positions [168]. Adducts of the di-enophile MTAD, which is formed with conjugated dienes via Diels-Alder cyclo-... 

In a comparative study, Jacobson et al. have shown that for the cis-fused cyclohexadiene, l,2,3,4,4a,8a-hexahydronaphthalene, the dienophilic reactivity follows the order PTAD > cis-DEAZD > trans-DEAZD, while the order is reversed for their reactivity as enophiles.67 Other studies have produced similar conclusions.21,54 In general, azo compounds give more ene product than the corresponding C=C compounds. 

This review has attempted to bring together the reactions of ADC compounds which are useful in heterocyclic synthesis, and to develop the general trends that have so far appeared in their reactivity. Thus, in general, ADC compounds are more powerful dienophiles than the corresponding C=C compounds, particularly when the azo bond is in the cis configuration. However, they are also more reactive as enophiles and electrophiles, and may react as such even in cases where Diels-Alder (or other) cycloaddition is formally possible, and where the corresponding C=C compounds do react as dienophiles. Nevertheless, despite this added complication, the major use of ADC compounds has been as dienophiles in the synthesis of pyridazines... 

Other reactions shown to occur at the same rate under the two heating methods include the acid-catalyzed isomerization of carvone 40 to carvacrol 41 [33], and ene reactions involving carbonyl enophiles (Scheme 4.21) [32], The former reaction was performed in a mixture of chlorobenzene (slightly polar) and dioxane (nonpolar) and in the latter reaction a large excess of 1-decene was used and so the reaction was effectively performed in a solution of low polarity. 

The ene reaction (or Alder reaction) is a cycloaddition which requires an activation energy higher than that of the Diels-Alder reaction [41]. Without a catalyst it usually occurs under pressure and/or at high temperature. The reaction with an allcene (ene) is much easier if the latter is more substituted (high HOMO) and the enophile is more electron-poor (low LUMO). 

Sulfur compounds are renowned for unpleasant odors beginning with the rotten egg smell of H2S and many are responsible for the off-flavors of various foods. Nevertheless, some sulfur compounds provide the pleasant odors associated with many plants and are also prominent in desirable food flavors. The determination of flavor or aroma is very complex since large numbers of components may be involved both for microorganisms and plants. Many flavor compounds, of course, do not contain sulfur. Much has been and continues to be written. We can only convey an eclectic flavor of the many situations involving sulfur compounds - a tasting menu. The colorful language of experts in aroma and taste bears a close resemblance to that of enophiles. 

Song and Beak161 have used intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects to investigate the mechanism of the tin tetrachloride catalysed ene-carbonyl enophile addition reaction between diethyloxomalonate and methylenecy-clohexane (equation 105). These ene reactions with carbonyl enophiles can occur by a concerted (equation 106) or a stepwise mechanism (equation 107), where the formation of the intermediate is either fast and reversible and the second step is slow k- > k-i), or where the formation of the intermediate (the k step) is rate-determining. 

Rather than the expected [3 + 2] cycloaddition, a novel ene-like cycloisomerization occurs on deprotonation of allyltrimethylsilyl-oxime compounds, when the j3-sp2 carbon atom of the allyltrimethylsilyl moiety is tethered to the oxime unit. The resulting nitrile oxide group serves as an enophile, and the final cyclized product still has two functional groups suitable for further manipulations. Thus, ene-like cycloisomerization of allyltrimethylsilyl-oxime 375 with NaOCl in CH2CI2 gives 82% of cyclized product 376 (423). See also Reference 424. 

The ene reaction, an electronic relative of the Diels-Alder cycloaddition, is a six-electron process involving the reaction of the n and allylic reactions these reactions are reviewed in detail (for reviews of the Alder-ene reaction and related chemistry, see Refs 1,1a, and lb). Recent developments in the area of hetero-ene chemistry (X1 = H, X2 = N,0) are also surveyed. 

Trost et al 2 briefly explored using non-enone enophiles. Simple alkenes led to the formation of complex mixtures of isomers due to the presence of an additional set of /3-hydrogens. Many other types of substrates were incompatible with reaction conditions. Vinyl ketones were, therefore, the only coupling partners shown to be effective in the ruthenium-catalyzed Alder-ene couplings of allenes and alkenes. 

The carbonyl group in a ketone or aldehyde is an extremely versatile vehicle for the introduction of functionality. Reaction can occur at the carbonyl carbon atom using the carbonyl group as an electrophile or through enolate formation upon removal of an acidic proton at the adjacent carbon atom. Although the carbonyl group is an integral part of the nucleophile, a carbonyl compound can also be considered as an enophile when involved in an asymmetric carbonyl-ene reaction or dienophile in an asymmetric hetero Diels-Alder reaction. These two types of reaction are discussed in the next three chapters. 

H. Laurent-Robert, C. Le Roux, J. Dubac, Enhancement of Dienophilic and Enophilic Readivity of the Gly-oxylic Acid by Bismuthfln) Triflate in the Presence of Water Synlett. 1998,1138-1140. 

An interesting pyrrolo[l,2-tf]pyrimidine was described as the product of the reaction of the heterocyclic ketene-aminals 236 that was synthesized by cyclocondensation of ketene dithioacetals 237 and 1,3-diamino propane. These compounds reacted with diethyl oxomalonate that behaves as an hetero-enophile, yielding the corresponding products 238 in acceptable to good yield (Scheme 31). A mechanism that involves an aza-ene reaction, via adduct 239 which isomerizes to ketene aminal 240 to produce the lactam ring of 238, has been proposed <1999J(P1)321>. 

Reaction of 3-methyleneindolines with enophiles We have observed that the isomerization of the methyleneindolines 9 to their aromatic methylindoles 2 isomers, did not take place just after the addition of the electrophiles but on the workup or silica gel chromatography of the reaction. Buchwald et al.[17fhi] demonstrated that 3-methylenindolines could un-... 

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