Ketones and aldehydes a, p-unsaturated

Aldol condensation offers an effective route to a p unsaturated aldehydes and ketones These compounds have some interesting properties that result from conjugation of the carbon-carbon double bond with the carbonyl group As shown m Figure 18 6 the rr systems of the carbon-carbon and carbon-oxygen double bonds overlap to form an extended rr system that permits increased electron delocalization... 

FIGURE 18 7 Nucleophilic addition to a p unsaturated aldehydes and ketones may take place either in a 1 2 or 1 4 manner Direct addition (1 2) occurs faster than conjugate addition (1 4) but gives a less stable product The product of 1 4 addition retains the carbon-oxygen double bond which is in general stronger than a carbon-carbon double bond... 

The preparation and some synthetic applications of lithium dialkylcuprates were described earlier (Section 14 11) The most prominent feature of these reagents is then-capacity to undergo conjugate addition to a p unsaturated aldehydes and ketones... 

Dijbner-von Miller Synthesis. A much less violent synthetic pathway, the Dn bner-von Miller, uses hydrochloric acid or 2inc chloride as the catalyst (43). As in the modified Skraup, a,P-unsaturated aldehydes and ketones make the dehydration of glycerol uimecessary, and allow a wider variety of substitution patterns. No added oxidant is required. With excess aniline the reaction proceeds as follows ... 

Xanthates have been added to activated double bonds, eg, acryhc derivatives and a,P-unsaturated aldehydes and ketones (59—61) ... 

The diminished tt electron density in the double bond makes a,p-unsaturated aldehydes and ketones less reactive than alkenes toward electrophilic addition. Electrophilic reagents—bromine and peroxy acids, for example—react more slowly with the carbon-carbon double bond of a,(3-unsaturated carbonyl compounds than with simple alkenes. 

The product is a P-hydroxy aldehyde (called an aldol) or ketone, which in some cases is dehydrated during the course of the reaction. Even if the dehydration is not spontaneous, it can usually be done easily, since the new double bond is in conjugation with the C=0 bond so that this is a method of preparing a,P-unsaturated aldehydes and ketones as well as P-hydroxy aldehydes and ketones. The entire reaction is an equilibrium (including the dehydration step), and a,P-unsaturated and P-hydroxy aldehydes and ketones can be cleaved by treatment with OH (the retrograde aldol reaction). There is evidence that an SET mechanism can intervene when the substrate is an aromatic ketone. ... 

When unsymmetrical ketones were used in this reaction (with BF3 as catalyst), the less highly substituted carbon preferentially migrated. The reaction can be made regioselective by applying this method to the a-halo ketone, in which case only the other carbon migrates. The ethyl diazoacetate procedure has also been applied to the acetals or ketals of a, P-unsaturated aldehydes and ketones. ... 

C02Et Br KOf-Bu/THF/-20°C aliphatic and aromatic aldehydes aliphatic, cycloaliphatic and aromatic ketone, a,p-unsaturated aldehydes and ketones 52-90... 

Additionally, investigations into imidazolidinone catalysed Diels-Alder reactions (Schemes 2 and 6) [234] have shown that iminium ions of a,P-unsaturated aldehydes and ketones have lower activation barriers for the Diels-Alder reaction with cyclopentadiene than the parent compound (13 and 11 kCal mol", respectively). It was also noted that transition structures show the formation of the bonds is concerted but highly asynchronous. 

Substrate scope - can a universal catalyst be developed for the activation of any a,P-unsaturated aldehyde and ketone with multiple substitutions ... 

For a review, sec Nigh, in Trahanovsky Oxidation in Organic Chemistry, pt. B Academic Press New York, 1973. pp. 67-81. Cupric chloride has been used to chlorinate a.p-unsaturated aldehydes and ketones in the y position Dietl Normark Payne Thweatl Young Tetrahedron Lett. 1973, 1719. 

As we have already seen, delocalization of electrons by conjugation decreases the energy difference between the HOMO and LUMO energy levels, and this leads to a red shift. Alkyl substitution on a conjugated system also leads to a (smaller) red shift, due to the small interaction between the cr-bonded electrons of the alkyl group with the K-bond system. These effects are additive, and the empirical Woodward-Fieser rules were developed to predict the 2max values for dienes (and trienes). Similar sets of rules can be used to predict the A ax values for a,P-unsaturated aldehydes and ketones (enones) and the Amax values for aromatic carbonyl compounds. These rules are summarized in Table 2.4. 

Using the Woodward-Fieser rules, the of dienes and trienes, a,p-unsaturated aldehydes and ketones (enones), and for aromatic carbonyl compounds can be reliably calculated and predicted. 

Definition a, p-Unsaturated aldehydes and ketones are aldehydes and ketones that are conjugated with a double bond. The a-position is defined as the carbon atom next to the carbonyl group, while the P-position is the carbon atom two bonds removed ... 

The carbonyl group of a,P-unsaturated aldehydes and ketones are made up nucleophilic oxygen and an electrophilic carbon. However, a,P-unsaturated aldehydes and ketones also have another electrophilic carbon—the p-carbon. This is because of the influence of the electronegative oxygen that can result in the... 

The mechanism of 1,2-nucleophilic addition is the same as already described. It is found that Grignard reagents and organolithium reagents will react with a,p-unsaturated aldehydes and ketones in this way and do not attack the p-position ... 

Conjugate addition to a,P-unsaturated aldehydes and ketones (Section 19.13). 

Aldol products are easily dehydrated to yield a,p-unsaturated aldehydes and ketones. 

One of the most effective approaches to implementing the Diels-Alder participation of 1-oxa-1,3-butadienes is through the use of an intramolecular [4 + 2] cycloaddition reaction.A select set of thermal and Lewis acid-catalyzed intramolecular cycloaddition reactions of unactivated and electron-rich alkenes with a,P-unsaturated aldehydes and ketones has been detailed. Two examples of the poorly matched intramolecular Diels-Alder reaction of an a,P-unsaturated aldehyde (4 ir component) with an a, 3-unsaturated amide (2ir component) have proven successful (190-160 °C) and may be attributed to the entropic assistance provided by the intramolecular reaction. These observations have been applied in... 

J.2.2 a,p-Unsaturated Aldehydes and Ketones 4J23 Acyclic Allylic Alcohols... 

The key step in the synthesis of 2-deoxycrustecdysone from the corresponding 20-oxo steroid is the stereoselective catalytic hydrogenation of the a,(3-unsaturated lactone to afford a 2 3 mixture of 8- and "y-lactones, respectively. This crude product was converted into the thermodynamically more stable y-lactone by treatment with aqueous NaOH. a,p-Unsaturated aldehydes and ketones are hydrogenated to produce allylic alcohols in high regioselectivity using hydridoiridium phosphine complexes, such as [Ir(PEt2Ph)4]4. 5 ... 

The reduction of a,p-unsaturated aldehydes and ketones by NaBH4 leads, in general, to substantial amounts of fully saturated alcohols. In alcoholic solvents, saturated -alkoxy alcohols can be formed via conjugate addition of the solvent. This latter process becomes the main reaction path when reduction is performed in 2-propanol in the presence of sodium isopropoxide. In base, a homoallylic alcohol can become the major product of borohydride reduction of an enone. Analysis of the influence of substrate structure on NaBH4 reduction has shown that increasing steric hindrance on the enone increases 1,2-attack. ... 

Sodium cyanoborohydride (NaBHsCN) or tetrabutylammonium cyanoborohydride in acidic methanol or acidic HMPA reduces a,p-unsaturated aldehydes and ketones to the corresponding allylic alcohols. This system is limited to enones in which the double bond is not further conjugated, in which case the allylic hydrocarbon is formed in substantial amounts. Thus, reduction of chalcone gives mainly 1,3-di-phenylpropene (48%) as well as 26% of the allylic ether. Cyclic enones are also not good substrates, as competing 1,4-addition gives large fractions of saturated alcohols. ... 

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