Double bond enols

The reaction conditions applied are usually heating the amine with a slight excess of aldehyde and a considerable.excess of 2d-30hydrochloric acid at 100 °C for a few hours, but much milder ( physiological ) conditions can be used with good success. Diols, olefinic double bonds, enol ethers, and glycosidic bonds survive a Pictet-Spengler reaction very well, since phenol and indole systems are much more reactive than any of these acid sensitive functional groups (W.M. Whaley, 1951 J.E.D. Barton, 1965 A.R. Battersby, 1969). 

In contrast to that of benzyl methyl ketone, deuteriation (or dedeuteriation) of methoxyacetone occurs preferentially at the methyl group in acidic conditions (Bothner-By and Sun, 1967 Hine et al., 1967a Chevallier et al., 1969). The peculiarity of this result has been emphasised by Hine. Indeed, since the methoxy group is expected to stabilise the double bond, enol [501 must be more stable than enol [511. This conclusion is supported by the ab initio calculations of Hehre and Lathan (1972). 

Like other compounds with carbon-carbon double bonds, enols are electron rich, so they react as nucleophiles. Enols are even more electron rich than alkenes, though, because the OH group has a powerful electron-donating resonance effect. A second resonance structure can be drawn for the enol that places a negative charge on one of the carbon atoms. As a result, this carbon atom is especially nucleophilic, and it can react with an electrophile to form a new bond to carbon. Loss of a proton then forms a neutral product. 

As the oxygen atom can donate a lone pair of electrons to the double bond, enols are more nucleophilic than alkenes... 

The addition of strongly polarized carbon-carbon double bonds (enols) to simple iminium ions, known as the Mannich reaction (equation 1), is a fundamentally important route to amines, especially in biosynthetic processes. 2 This reaction type is less synthetically useful if weakly polarized or unpolarized carbon-carbon iT-bonds are used as nucleophiles (equation 2). Because of the low electrophilic reactivity of the iminium moiety, the reverse reaction, known as the Grob fragmentation (equation 2), is often the more important process. However, if the iminium moiety has a carbonyl substituent on nitrogen, its... 

I, 5-dicarbonyl compounds and their interesting and varied chemistry, e.g., the formation of cyclohexenones from aldol condensation of the products. As an extension of the de Mayo reaction (the photocycloaddition of enolated /i-diketones to double bonds) enol esters, enol ethers, vinylogous esters and amides, and dioxinone have been employed as the enone components. Some intermolecular examples have already been discussed in Section 1.6.1.4.2.1.6. (cf. Table 4, entries 2 and 3) and some intramolecular systems are collected in Table 5, entries 10,... 

Under acidic conditions, monohalogenation is the usuai outcome, but in base, poiyhaio-genation is more common. The iodoform reaction converts methyi ketones to carboxyiic acids and iodoform, CHI3, and can be used as a test for the presence of this functionaiity. Generally, the stability of enols Is enhanced by substitution at the double bond. Enolates, by contrast, are most easily formed at unsubstituted positions. 

When a mixture of aniline, nitrobenzene, glycerol and concentrated sulphuric acid is heated, a vigorous reaction occurs with the formation of quinoline. It is probable that the sulphuric acid first dehydrates the glycerol giving acrolein or acraldehyde (A), which then condenses at its double bond with the amino group of the aniline to give acrolein-aniline (B), The latter in its enol... 

The condensation conditions must be as mild as possible, because we want to get only the most stable of the three possible enols (from the aldehyde). Though you could not haye predicted the exact conditions either for the double bond. cleayage or for the condensation, you should haye seen that control was possible as in each case the two functional groups are different enough. ( J. Amer. Chem. Soc.. 1960, 636 J. Org. Chem.. 1964, 29, 3740 ... 

The addition of large enolate synthons to cyclohexenone derivatives via Michael addition leads to equatorial substitution. If the cyclohexenone conformation is fixed, e.g. as in decalones or steroids, the addition is highly stereoselective. This is also the case with the S-addition to conjugated dienones (Y. Abe, 1956). Large substituents at C-4 of cyclic a -synthons direct incoming carbanions to the /rans-position at C-3 (A.R. Battersby, 1960). The thermodynamically most stable products are formed in these cases, because the addition of 1,3-dioxo compounds to activated double bonds is essentially reversible. 

If a Michael reaction uses an unsymmetrical ketone with two CH-groups of similar acidity, the enol or enolate is first prepared in pure form (p. llff.). To avoid equilibration one has to work at low temperatures. The reaction may then become slow, and it is advisable to further activate the carbon-carbon double bond. This may be achieved by the introduction of an extra electron-withdrawing silyl substituent at C-2 of an a -synthon. Treatment of the Michael adduct with base removes the silicon, and may lead as well to an aldol addition (G. Stork, 1973, 1974 B R.K. Boeckman, Jr., 1974). 

Selective reduction of a benzene ring (W. Grimme, 1970) or a C C double bond (J.E. Cole, 1962) in the presence of protected carbonyl groups (acetals or enol ethers) has been achieved by Birch reduction. Selective reduction of the C—C double bond of an a,ft-unsaturated ketone in the presence of a benzene ring is also possible in aprotic solution, because the benzene ring is redueed only very slowly in the absence of a proton donor (D. Caine, 1976). 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Pd hydride. Subsequent enolate formation, double bond isomerization, and carbonylation give the butenolide 582. 

By analogy to the hydration of alkenes hydration of an alkyne is expected to yield an alcohol The kind of alcohol however would be of a special kind one m which the hydroxyl group is a substituent on a carbon-carbon double bond This type of alcohol IS called an enol (the double bond suffix ene plus the alcohol suffix ol) An important property of enols is their rapid isomerization to aldehydes or ketones under the condi tions of their formation... 

The first step protonation of the double bond of the enol is analogous to the pro tonation of the double bond of an alkene It takes place more readily however because the carbocation formed m this step is stabilized by resonance involving delocalization of a lone pair of oxygen... 

Step 1 The enol is formed in aqueous acidic solution The first step of its transformation to a ketone is proton transfer to the carbon-carbon double bond... 

Both parts of the Lapworth mechanism enol formation and enol halogenation are new to us Let s examine them m reverse order We can understand enol halogenation by analogy to halogen addition to alkenes An enol is a very reactive kind of alkene Its carbon-carbon double bond bears an electron releasing hydroxyl group which makes it electron rich and activates it toward attack by electrophiles... 

Participation by the oxygen lone pairs is responsible for the rapid attack on the carbon-carbon double bond of an enol by bromine We can represent this participation explicitly... 

Writing the bromine addition step m this way emphasizes the increased nucleophilicity of the enol double bond and identifies the source of that increased nucleophilicity as the enolic oxygen... 

In these and numerous other simple cases the keto form is more stable than the enol by some 45-60 kJ/mol (11-14 kcal/mol) The chief reason for this difference is that a carbon-oxygen double bond is stronger than a carbon-carbon double bond... 

Both enols have their carbon-carbon double bonds conjugated to a carbonyl group and can form an intramolecular hydrogen bond They are of comparable stability... 

With certain other nucleophiles addition takes place at the carbon-carbon double bond rather than at the carbonyl group Such reactions proceed via enol intermediates and are described as conjugate addition ox 1 4 addition reactions... 

Ordinarily nucleophilic addition to the carbon-carbon double bond of an alkene is very rare It occurs with a p unsaturated carbonyl compounds because the carbanion that results IS an enolate which is more stable than a simple alkyl anion... 

Hydroperoxides have been obtained from the autoxidation of alkanes, aralkanes, alkenes, ketones, enols, hydrazones, aromatic amines, amides, ethers, acetals, alcohols, and organomineral compounds, eg, Grignard reagents (10,45). In autoxidations involving hydrazones, double-bond migration occurs with the formation of hydroperoxy—azo compounds via free-radical chain processes (10,59) (eq. 20). 

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